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1.  Are Women Who Smoke at Higher Risk for Lung Cancer Than Men Who Smoke? 
American Journal of Epidemiology  2013;177(7):601-612.
Worldwide lung cancer incidence is decreasing or leveling off among men, but rising among women. Sex differences in associations of tobacco carcinogens with lung cancer risk have been hypothesized, but the epidemiologic evidence is conflicting. We tested sex-smoking interaction in association with lung cancer risk within a population-based case-control study, the Environment and Genetics in Lung Cancer Etiology (EAGLE) Study (Lombardy, Italy, 2002–2005). Detailed lifetime smoking histories were collected by personal interview in 2,100 cases with incident lung cancer and 2,120 controls. Odds ratios and 95% confidence intervals for pack-years of cigarette smoking were estimated by logistic regression, adjusted for age, residence area, and time since quitting smoking. To assess sex-smoking interaction, we compared the slopes of odds ratios for logarithm of pack-years in a model for men and women combined. Overall, the slope for pack-years was steeper in men (odds ratio for female-smoking interaction = 0.39, 95% confidence interval: 0.24, 0.62; P < 0.0001); after restriction to ever smokers, the difference in slopes was much smaller (odds ratio for interaction = 0.63, 95% confidence interval: 0.29, 1.37; P = 0.24). Similar results were found by histological type. Results were unchanged when additional confounders were evaluated (e.g., tobacco type, inhalation depth, Fagerström-assessed nicotine dependence). These findings do not support a higher female susceptibility to tobacco-related lung cancer.
doi:10.1093/aje/kws445
PMCID: PMC3657535  PMID: 23425629
case-control studies; lung cancer; sex differences; smoking
2.  Alcohol Consumption at Midlife and Successful Ageing in Women: A Prospective Cohort Analysis in the Nurses' Health Study 
PLoS Medicine  2011;8(9):e1001090.
Using the Nurses' Health Study, Qi Sun and colleagues examine whether moderate alcohol intake is associated with overall health and well-being among women who survive to older age.
Background
Observational studies have documented inverse associations between moderate alcohol consumption and risk of premature death. It is largely unknown whether moderate alcohol intake is also associated with overall health and well-being among populations who have survived to older age. In this study, we prospectively examined alcohol use assessed at midlife in relation to successful ageing in a cohort of US women.
Methods and Findings
Alcohol consumption at midlife was assessed using a validated food frequency questionnaire. Subsequently, successful ageing was defined in 13,894 Nurses' Health Study participants who survived to age 70 or older, and whose health status was continuously updated. “Successful ageing” was considered as being free of 11 major chronic diseases and having no major cognitive impairment, physical impairment, or mental health limitations. Analyses were restricted to the 98.1% of participants who were not heavier drinkers (>45 g/d) at midlife. Of all eligible study participants, 1,491 (10.7%) achieved successful ageing. After multivariable adjustment of potential confounders, light-to-moderate alcohol consumption at midlife was associated with modestly increased odds of successful ageing. The odds ratios (95% confidence interval) were 1.0 (referent) for nondrinkers, 1.11 (0.96–1.29) for ≤5.0 g/d, 1.19 (1.01–1.40) for 5.1–15.0 g/d, 1.28 (1.03–1.58) for 15.1–30.0 g/d, and 1.24 (0.87–1.76) for 30.1–45.0 g/d. Meanwhile, independent of total alcohol intake, participants who drank alcohol at regular patterns throughout the week, rather than on a single occasion, had somewhat better odds of successful ageing; for example, the odds ratios (95% confidence interval) were 1.29 (1.01–1.64) and 1.47 (1.14–1.90) for those drinking 3–4 days and 5–7 days per week in comparison with nondrinkers, respectively, whereas the odds ratio was 1.10 (0.94–1.30) for those drinking only 1–2 days per week.
Conclusions
These data suggest that regular, moderate consumption of alcohol at midlife may be related to a modest increase in overall health status among women who survive to older ages.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
People have always drunk alcoholic beverages but throughout history there have been arguments about the risks and benefits of beer, wine, and spirits. It is clear that excessive alcohol use—heavy drinking (an average of more than two drinks per day for men or more than one drink per day for women; in the US, a “drink” is defined as 15 g of alcohol or, roughly speaking, a can of beer or a small glass of wine) or binge drinking (five or more drinks on a single occasion for men; 4 or more drinks at one time for women)—is harmful. It causes liver damage and increases the risk of developing some types of cancer. It contributes to depression and violence and interferes with relationships. And it is often implicated in fatal traffic accidents. However, in contrast to these and other harms associated with excessive alcohol use, moderate alcohol consumption seems to reduce the risk of specific diseases such as heart disease, stroke, and cognitive decline (deterioration in learning, reasoning, and perception).
Why Was This Study Done?
Although people who drink moderate amounts of alcohol have a reduced risk of premature death compared to abstainers or heavy drinkers, it is not known whether moderate alcohol consumption is associated with overall health among ageing populations. In many countries, elderly people are an increasingly large part of the population, so it is important to know how moderate alcohol consumption affects their well-being. In this study, the researchers examine the effect of alcohol consumption at midlife on successful ageing among the participants of the Nurses' Health Study. The researchers study the effect of midlife alcohol consumption because the chronic conditions that affect elderly people develop slowly and it is likely that factors in earlier life determine health in later life. Successful ageing is defined as being free of major chronic diseases such as cancer and heart disease, and having no major cognitive impairment, physical impairment, or mental health problems. The Nurses' Health Study enrolled 121,700 female registered nurses in 1976 to investigate the long-term effects of oral contraceptive use but has provided insights into many aspects of health and disease.
What Did the Researchers Do and Find?
The researchers assessed the alcohol consumption of the study participants at midlife (average age 58 years) from food frequency questionnaires completed in 1980 and 1984. Successful ageing for 13,984 participants who survived past 70 years was assessed by analyzing biennial health status questionnaires and cognitive function test results. One tenth of the women achieved successful ageing. After allowing for other factors that might affect their health such as smoking, women who drank light or moderate amounts of alcohol had a modestly increased chance of successful ageing compared to nondrinkers. For example, compared to nondrinkers, women who drank 5–15 g of alcohol per day (between one-third and one drink per day) had about a 20% higher chance of successful ageing. Independent of total alcohol intake, women who drank alcohol regularly had a better chance of successful ageing than occasional drinkers. Thus, compared to nondrinkers, women who drank five to seven days a week had nearly a 50% greater chance of successful ageing whereas women who drank only one or two days a week had a similar likelihood of successful ageing.
What Do These Findings Mean?
These findings suggest that regular, moderate consumption of alcohol at midlife may be related to a modest increase in overall health among women who survive to older ages. Because this is an observational study, it is possible that the women who drank moderately share other unknown characteristics that are actually responsible for their increased chance of successful ageing. Moreover, because all the study participants were women and most had European ancestry, these findings cannot be applied to men or to other ethnic groups. Nevertheless, these findings provide support for the 2010 US Department of Agriculture dietary guidelines, which state that consumption of up to one alcoholic drink per day for women and up to two alcoholic drinks per day for men may provide health benefits. Importantly, they also suggest that drinking alcohol regularly in moderation rather than occasional heavy drinking may be associated with a greater likelihood of successful ageing.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001090.
The US National Institute on Alcohol Abuse and Alcoholism has detailed information about alcohol and its effects on health, including a fact sheet on women and alcohol and a booklet entitled Alcohol, a woman's health issue
The US Centers for Disease Control and Prevention has a website on alcohol and public health
The UK National Health Service Choices website provides detailed information about drinking and alcohol, including how to calculate consumption
The Nutrition Source, a website maintained by the Department of Nutrition at Harvard School of Public Health, has an article entitled Alcohol: balancing risks and benefits
MedlinePlus provides links to many other resources on alcohol and on seniors' health
Details of the Nurses' Health Study are available
The 2010 US Department of Agriculture dietary guidelines are available
doi:10.1371/journal.pmed.1001090
PMCID: PMC3167795  PMID: 21909248
3.  Lung Cancer and Occupation in a Population-based Case-Control Study 
American Journal of Epidemiology  2010;171(3):323-333.
The authors examined the relation between occupation and lung cancer in the large, population-based Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study. In 2002–2005 in the Lombardy region of northern Italy, 2,100 incident lung cancer cases and 2,120 randomly selected population controls were enrolled. Lifetime occupational histories (industry and job title) were coded by using standard international classifications and were translated into occupations known (list A) or suspected (list B) to be associated with lung cancer. Smoking-adjusted odds ratios and 95% confidence intervals were calculated with logistic regression. For men, an increased risk was found for list A (177 exposed cases and 100 controls; odds ratio = 1.74, 95% confidence interval: 1.27, 2.38) and most occupations therein. No overall excess was found for list B with the exception of filling station attendants and bus and truck drivers (men) and launderers and dry cleaners (women). The authors estimated that 4.9% (95% confidence interval: 2.0, 7.8) of lung cancers in men were attributable to occupation. Among those in other occupations, risk excesses were found for metal workers, barbers and hairdressers, and other motor vehicle drivers. These results indicate that past exposure to occupational carcinogens remains an important determinant of lung cancer occurrence.
doi:10.1093/aje/kwp391
PMCID: PMC2808498  PMID: 20047975
carcinogens; case-control studies; industry; lung neoplasms; occupational health; occupations
4.  Mood Disorders and Risk of Lung Cancer in the EAGLE Case-Control Study and in the U.S. Veterans Affairs Inpatient Cohort 
PLoS ONE  2012;7(8):e42945.
Background
Mood disorders may affect lung cancer risk. We evaluated this hypothesis in two large studies.
Methodology/Principal Findings
We examined 1,939 lung cancer cases and 2,102 controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study conducted in Italy (2002–2005), and 82,945 inpatients with a lung cancer diagnosis and 3,586,299 person-years without a lung cancer diagnosis in the U.S. Veterans Affairs Inpatient Cohort (VA study), composed of veterans with a VA hospital admission (1969–1996). In EAGLE, we calculated odds ratios (ORs) and 95% confidence intervals (CI), with extensive adjustment for tobacco smoking and multiple lifestyle factors. In the VA study, we estimated lung cancer relative risks (RRs) and 95% CIs with time-dependent Poisson regression, adjusting for attained age, calendar year, hospital visits, time within the study, and related previous medical diagnoses. In EAGLE, we found decreased lung cancer risk in subjects with a personal history of mood disorders (OR: 0.59, 95% CI: 0.44–0.79, based on 121 lung cancer incident cases and 192 controls) and family history of mood disorders (OR: 0.62, 95% CI: 0.50–0.77, based on 223 lung cancer cases and 345 controls). The VA study analyses yielded similar results (RR: 0.74, 95% CI: 0.71–0.77, based on 2,304 incident lung cancer cases and 177,267 non-cancer person-years) in men with discharge diagnoses for mood disorders. History of mood disorders was associated with nicotine dependence, alcohol and substance use and psychometric scales of depressive and anxiety symptoms in controls for these studies.
Conclusions/Significance
The consistent finding of a relationship between mood disorders and lung cancer risk across two large studies calls for further research into the complex interplay of risk factors associated with these two widespread and debilitating diseases. Although we adjusted for smoking effects in EAGLE, residual confounding of the results by smoking cannot be ruled out.
doi:10.1371/journal.pone.0042945
PMCID: PMC3413657  PMID: 22880133
5.  Intakes of red meat, processed meat, and meat-mutagens increase lung cancer risk 
Cancer research  2009;69(3):932-939.
Red and processed meat intake may increase lung cancer risk. However, the epidemiologic evidence is inconsistent and few studies have evaluated the role of meat-mutagens formed during high cooking temperatures. We investigated the association of red meat, processed meat, and meat-mutagen intake with lung cancer risk in Environment And Genetics in Lung cancer Etiology (EAGLE), a population-based case-control study. Primary lung cancer cases (n=2101) were recruited from 13 hospitals within the Lombardy region of Italy examining ~80% of the cases from the area. Non-cancer population controls (n=2120), matched to cases on gender, residence, and age, were randomly selected from the same catchment area. Diet was assessed in 1903 cases and 2073 controls, and used in conjunction with a meat-mutagen database to estimate intake of heterocyclic amines and benzo[a]pyrene. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific tertiles of intake were calculated using unconditional logistic regression. Red and processed meat were positively associated with lung cancer risk (highest-versus-lowest tertile: OR=1.8; 95% CI=1.5–2.2; p-trend<0.001 and OR=1.7; 95% CI=1.4–2.1; p-trend<0.001, respectively); the risks were strongest among never smokers (OR=2.4, 95% CI=1.4–4.0, p-trend=0.001 and OR=2.5, 95% CI=1.5–4.2, p-trend=0.001, respectively). Heterocyclic amines and benzo[a]pyrene were significantly associated with increased risk of lung cancer. When separated by histology, significant positive associations for both meat groups were restricted to adenocarcinoma and squamous cell carcinoma, but not small cell carcinoma of the lung. In summary, red meat, processed meat, and meat-mutagens were independently associated with increased risk of lung cancer.
doi:10.1158/0008-5472.CAN-08-3162
PMCID: PMC2720759  PMID: 19141639
red meat; processed meat; meat-mutagens; cooking methods; lung cancer
6.  Effect of the interaction between the amount and duration of alcohol consumption and tobacco smoking on the risk of esophageal cancer: A case-control study 
The effects of alcohol consumption and tobacco smoking on the prevalence of esophageal cancer vary considerably by country, race and lifestyle. Few data exist on the effect of the interaction between the amount and duration of alcohol consumption and tobacco smoking on the incidence of esophageal cancer. In this case-control study, the cases included patients with histologically confirmed esophageal squamous cell carcinoma (ESCC) younger than 60 years of age and recruited between January 1, 2002 and December 31, 2006. The controls had no abnormality during a medical checkup. A total of 835 pairs were created by pairing each case to a gender- and age-matched control. Conditional logistic regression analysis was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals. Univariate conditional logistic regression analyses revealed that the ORs according to both duration of alcohol consumption and tobacco smoking increased monotonically. Alcohol consumption and tobacco smoking may have a synergistic effect on the incidence of ESCC. Conditional logistic regression analysis using a forward stepwise selection procedure revealed that the incidence of ESCC was associated with the duration of tobacco smoking, the interaction between the amount and duration of alcohol consumption, and a family history of cancer. In particular, groups with a long duration of alcohol consumption and high alcohol intake had much higher ORs than those with short duration and low intake, which highlights the importance of the interaction between the amount and duration of alcohol intake. This study confirmed the significance of the interaction between alcohol consumption and tobacco smoking in esophageal cancer. This interaction between amount and duration is an accurate indicator for estimating the risk of esophageal cancer attributable to alcohol consumption and tobacco smoking. These findings suggest that decreasing the number of young and middle-aged drinkers and smokers will reduce the incidence of esophageal cancer.
doi:10.3892/etm.2010.152
PMCID: PMC3446748  PMID: 22993631
alcohol consumption; tobacco smoking; esophageal cancer; interaction between amount and duration
7.  Chronic Obstructive Pulmonary Disease and Altered Risk of Lung Cancer in a Population-Based Case-Control Study 
PLoS ONE  2009;4(10):e7380.
Background
Chronic obstructive pulmonary disease (COPD) has been consistently associated with increased risk of lung cancer. However, previous studies have had limited ability to determine whether the association is due to smoking.
Methodology/Principal Findings
The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based case-control study recruited 2100 cases and 2120 controls, of whom 1934 cases and 2108 controls reported about diagnosis of chronic bronchitis, emphysema, COPD (chronic bronchitis and/or emphysema), or asthma more than 1 year before enrollment. We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. After adjustment for smoking, other previous lung diseases, and study design variables, lung cancer risk was elevated among individuals with a history of chronic bronchitis (OR = 2.0, 95% CI = 1.5–2.5), emphysema (OR = 1.9, 95% CI = 1.4–2.8), or COPD (OR = 2.5, 95% CI = 2.0–3.1). Among current smokers, association between chronic bronchitis and lung cancer was strongest among lighter smokers. Asthma was associated with a decreased risk of lung cancer in males (OR = 0.48, 95% CI = 0.30–0.78).
Conclusions/Significance
These results suggest that the associations of personal history of chronic bronchitis, emphysema, and COPD with increased risk of lung cancer are not entirely due to smoking. Inflammatory processes may both contribute to COPD and be important for lung carcinogenesis.
doi:10.1371/journal.pone.0007380
PMCID: PMC2753644  PMID: 19812684
8.  Alcohol and tobacco use in relation to gastric cancer: a prospective study of men in Shanghai, China 
Background
Epidemiological findings of tobacco and alcohol use in relation to gastric cancer are inconsistent. Well-designed prospective studies examining their relationship are sparse.
Methods
The association between cigarette smoking/alcohol intake and gastric cancer risk was examined in a population-based prospective cohort of 18,244 middle-aged and older men in Shanghai, China, who were enrolled in the study during 1986–1989. After up to 20 years of follow-up, 391 incident gastric cancer cases were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs).
Results
Ever smokers experienced a statistically significant increased risk of gastric cancer (HR, 1.59; 95% CI, 1.27–1.99) compared with nonsmokers after adjustment for alcohol intake and other confounders. Among nondrinkers, smokers experienced 80% increased risk of gastric cancer (HR, 1.81; 95% CI,1.36, 2.41). Conversely heavy drinkers experienced a statistically significant increase in risk of gastric cancer (HR, 1.46; 95% CI, 1.05–2.04) among all subjects and a statistically non-significant 80% increased risk among never smokers. Further adjustment for Helicobacter pylori serology, serum levels of beta-carotene and vitamin C, and urinary level of total isothiocyanates in combination with glutathione S-transferase (GST) M1 and GSTT1 genotypes did not materially change the associations between smoking/alcohol consumption and gastric cancer risk.
Conclusions
These results suggest that cigarette smoking and alcohol consumption may exert independent effects on the development of gastric cancer in this high-risk population.
Impact
Modification of these lifestyle choices may reduce the incidence of gastric cancer.
doi:10.1158/1055-9965.EPI-10-0362
PMCID: PMC2936659  PMID: 20699372
Alcohol; smoking; gastric cancer
9.  Esophageal cancer risk by type of alcohol drinking and smoking: a case-control study in Spain 
BMC Cancer  2008;8:221.
Background
The effect of tobacco smoking and alcohol drinking on esophageal cancer (EC) has never been explored in Spain where black tobacco and wine consumptions are quite prevalent. We estimated the independent effect of different alcoholic beverages and type of tobacco smoking on the risk of EC and its main histological cell type (squamous cell carcinoma) in a hospital-based case-control study in a Mediterranean area of Spain.
Methods
We only included incident cases with histologically confirmed EC (n = 202). Controls were frequency-matched to cases by age, sex and province (n = 455). Information on risk factors was elicited by trained interviewers using structured questionnaires. Multiple logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals (CI).
Results
Alcohol drinking and tobacco smoking were strong and independent risk factors for esophageal cancer. Alcohol was a potent risk factor with a clear dose-response relationship, particularly for esophageal squamous-cell cancer. Compared to never-drinkers, the risk for heaviest drinkers (≥ 75 g/day of pure ethanol) was 7.65 (95%CI, 3.16–18.49); and compared with never-smokers, the risk for heaviest smokers (≥ 30 cigarettes/day) was 5.07 (95%CI, 2.06–12.47). A low consumption of only wine and/or beer (1–24 g/d) did not increase the risk whereas a strong positive trend was observed for all types of alcoholic beverages that included any combination of hard liquors with beer and/or wine (p-trend<0.00001). A significant increase in EC risk was only observed for black-tobacco smoking (2.5-fold increase), not for blond tobacco. The effects for alcohol drinking were much stronger when the analysis was limited to the esophageal squamous cell carcinoma (n = 160), whereas a lack of effect for adenocarcinoma was evidenced. Smoking cessation showed a beneficial effect within ten years whereas drinking cessation did not.
Conclusion
Our study shows that the risk of EC, and particularly the squamous cell type, is strongly associated with alcohol drinking. The consumption of any combination of hard liquors seems to be harmful whereas a low consumption of only wine may not. This may relates to the presence of certain antioxidant compounds found in wine but practically lacking in liquors. Tobacco smoking is also a clear risk factor, black more than blond.
doi:10.1186/1471-2407-8-221
PMCID: PMC2529333  PMID: 18673563
10.  Inverse associations between light-to-moderate alcohol intake and lipid-related indices in patients with diabetes 
Background
Dyslipidemia is a common complication in patients with diabetes and is involved in being prone to cardiovascular disease. The risk of coronary artery disease is known to be lower in light-to-moderate drinkers than in abstainers. The aim of this study was to clarify whether and how alcohol drinking influences the lipid-related indices, good predictors for cardiovascular disease, such as the ratio of LDL cholesterol to HDL cholesterol (LDL-C/HDL-C ratio), the ratio of triglycerides to HDL cholesterol (TG/HDL-C ratio), and the lipid accumulation product (LAP), in patients with diabetes.
Methods
The subjects were men with diabetes (n = 1477; mean age, 54.0 years) and they were divided into non-, light (< 22 g ethanol/day), moderate (≥ 22 and < 44 g ethanol/day) and heavy (≥ 44 g ethanol/day) drinkers. The relationships between alcohol intake and the lipid-related indices were investigated by the multivariate analyses with adjustment for age, smoking, regular exercise and drug therapy for diabetes.
Results
The odds ratio (OR) vs. nondrinkers for high LDL-C/HDL-C ratio tended to be lower with an increase in alcohol intake (OR with 95% confidence interval (CI): 0.80 [0.50-1.29] in light drinkers; 0.24 [0.15-0.38] in moderate drinkers and 0.10 [0.05-0.19] in heavy drinkers). Alcohol intake showed an inverse association with a high TG/HDL-C ratio (OR with 95% CI vs. nondrinkers for high TG/HDL-C ratio: 0.54 [0.36-0.80] in light drinkers; 0.73 [0.56-0.97] in moderate drinkers and 0.72 [0.53-0.98] in heavy drinkers) and a J-shaped relationship with a high LAP (OR with 95% CI vs. nondrinkers for high LAP: 0.66 [0.43-1.02] in light drinkers; 0.82 [0.61-1.10] in moderate drinkers, and 1.29 [0.95-1.77] in heavy drinkers). Similar associations between alcohol intake and the lipid indices were obtained in a covariance analysis.
Conclusions
In patients with diabetes, light-to-moderate alcohol consumption is inversely associated with lipid-related indices, and this correlates with previous findings of cardiovascular risk reduction by modest drinking in patients with diabetes.
doi:10.1186/1475-2840-12-104
PMCID: PMC3723450  PMID: 23866006
11.  A Population-Based Study on Alcohol and High-Risk Sexual Behaviors in Botswana 
PLoS Medicine  2006;3(10):e392.
Background
In Botswana, an estimated 24% of adults ages 15–49 years are infected with HIV. While alcohol use is strongly associated with HIV infection in Africa, few population-based studies have characterized the association of alcohol use with specific high-risk sexual behaviors.
Methods and Findings
We conducted a cross-sectional, population-based study of 1,268 adults from five districts in Botswana using a stratified two-stage probability sample design. Multivariate logistic regression was used to assess correlates of heavy alcohol consumption (>14 drinks/week for women, and >21 drinks/week for men) as a dependent variable. We also assessed gender-specific associations between alcohol use as a primary independent variable (categorized as none, moderate, problem and heavy drinking) and several risky sex outcomes including: (a) having unprotected sex with a nonmonogamous partner; (b) having multiple sexual partners; and (c) paying for or selling sex in exchange for money or other resources. Criteria for heavy drinking were met by 31% of men and 17% of women. Adjusted correlates of heavy alcohol use included male gender, intergenerational relationships (age gap ≥10 y), higher education, and living with a sexual partner. Among men, heavy alcohol use was associated with higher odds of all risky sex outcomes examined, including unprotected sex (AOR = 3.48; 95% confidence interval [CI], 1.65 to 7.32), multiple partners (AOR = 3.08; 95% CI, 1.95 to 4.87), and paying for sex (AOR = 3.65; 95% CI, 2.58 to 12.37). Similarly, among women, heavy alcohol consumption was associated with higher odds of unprotected sex (AOR = 3.28; 95% CI, 1.71 to 6.28), multiple partners (AOR = 3.05; 95% CI, 1.83 to 5.07), and selling sex (AOR = 8.50; 95% CI, 3.41 to 21.18). A dose-response relationship was seen between alcohol use and risky sexual behaviors, with moderate drinkers at lower risk than both problem and heavy drinkers.
Conclusions
Alcohol use is associated with multiple risks for HIV transmission among both men and women. The findings of this study underscore the need to integrate alcohol abuse and HIV prevention efforts in Botswana and elsewhere.
Alcohol use is associated with multiple risks for HIV transmission in men and women. The findings underscore the need to integrate alcohol abuse and HIV prevention efforts in Botswana and elsewhere.
Editors' Summary
Background.
Human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS), is most commonly spread through unprotected sex with an infected partner. HIV enters the body through the lining of the sex organs, rectum, or mouth, and destroys immune system cells, leaving the infected person susceptible to other viruses and bacteria. Although HIV education and prevention campaigns emphasize the importance of safe sex in reducing HIV transmission, people continue to become infected by having unprotected sex (that is, not using a condom) with either a nonmonogamous partner or multiple sexual partners, or in situations where they are paying for or selling sex. Research in different populations suggested that heavy alcohol use is associated with risky sexual behaviors. This is because alcohol relaxes the brain and body, reduces inhibitions, and diminishes risk perception. Drinking alcohol may further increase the risk of becoming infected with HIV through its suppressive effects on the immune system.
Why Was This Study Done?
Alcohol abuse is widespread in sub-Saharan Africa where most HIV infections occur and has been associated with risky sexual behaviors. It may therefore be one of the most common, potentially modifiable HIV risk factors in this region. However, research to date has concentrated on the association between alcohol consumption and risky sex in people attending HIV-treatment clinics or recruited at beer halls, and these populations may not be representative of the general population of sub-Saharan Africa. In this study, the researchers have investigated the potential role of alcohol in perpetuating the HIV epidemic by undertaking a population-based study on alcohol use and high-risk sexual behaviors in Botswana. Nearly a quarter of adults are infected with HIV here, and alcohol abuse is also common, particularly in the townships.
What Did the Researchers Do and Find?
The researchers recruited a random cross-section of people from the five districts of Botswana with the highest number of HIV-infected individuals and interviewed all 1,268 participants using a questionnaire. This included general questions about the participants (for example, their age and marital status) and questions about alcohol use, sexual behavior, and knowledge of HIV. Overall, 31% of the men in the study and 17% of the women were heavy drinkers—more than 21 drinks/week for men, 14 for women; a drink is half a pint of beer or a glass of wine. Heavy alcohol use was associated with being male, being in an intergenerational relationship (at least 10 years age difference between partners; intergenerational sex facilitates the continued spread of HIV in sub-Saharan Africa), having had more education, and living with a sexual partner. Among men, those who drank heavily were three to four times more likely to have unprotected sex or multiple partners or to pay for sex than nondrinkers. Among women, there was a similar association between heavy drinking and having unprotected sex or multiple partners, and heavy drinkers were eight times as likely to sell sex as nondrinkers. For both men and women, the more they drank, the more likely they were to have risky sex. The study did not address behavior among same-sex partnerships.
What Do These Findings Mean?
This study indicates that heavy alcohol consumption is strongly and consistently associated with sexual risk behaviors in both men and women in Botswana. Because of the study design, it does not prove that heavy alcohol use is the cause of such behaviors but provides strong circumstantial evidence that this is the case. It is possible that these results may not apply to neighboring African countries—Botswana is unique in being relatively wealthy and in its government being strongly committed to tackling HIV. Nevertheless, taken together with the results of other studies, this research strongly argues for the need to deal with alcohol abuse within HIV prevention programs in sub-Saharan Africa. Strategies to do this could include education campaigns that target both alcohol use and HIV in schools and in social venues, including beer halls. But, stress the researchers, any strategy that is used must consider the cultural and social significance of alcohol use (in Botswana, alcohol use is a symbol of masculinity and high socioeconomic status) and must simultaneously tackle not only the overlap between alcohol use and risky sexual behavior but also the overlap between alcohol and other risk behaviors such as intergenerational sex.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030392.
US National Institute of Allergy and Infectious Diseases factsheet on HIV infection and AIDS
US Department of Health and Human Services information on AIDS
US Centers for Disease Control and Prevention information on HIV/AIDS
US National Institute on Alcohol Abuse and Alcoholism patient information on alcohol and HIV/AIDS]
Aidsmap, information on HIV and AIDS provided by the charity NAM,which includes some information on HIV infections and alcohol
AVERT information on HIV and AIDS in Botswana
doi:10.1371/journal.pmed.0030392
PMCID: PMC1592342  PMID: 17032060
12.  Associations of Cigarette Smoking and Alcohol Consumption With Metabolic Syndrome in a Male Chinese Population: A Cross-Sectional Study 
Journal of Epidemiology  2014;24(5):361-369.
Background
Whether cigarette smoking and alcohol consumption are associated with the risk of metabolic syndrome (MetS) remains controversial. This study investigated the associations of cigarette smoking and alcohol consumption with MetS in a male population in China.
Methods
We conducted a cross-sectional study. A questionnaire was used to collect data on cigarette smoking, alcohol consumption, MetS status, and other related information from 8169 men aged 19–97 years. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between smoking and alcohol consumption and the risk of MetS.
Results
The prevalence of MetS was 15.2% in the study population. Proportions of current smokers and drinkers were 48.2% and 46.5%, respectively. Adjusted OR of MetS was 1.34 (95% CI, 1.01–1.79) among smokers who smoked ≥40 cigarettes/day compared with nonsmokers and 1.22 (95% CI 1.03–1.46) for those who consumed 0.1–99 grams of alcohol/day compared with nondrinkers. Adjusted OR was 2.32 (95% CI 1.45–3.73) among ex-drinkers who never smoked, 1.98 (95% CI 1.35–2.91) among ex-drinkers who were current smokers, and 1.34 (95% CI 1.08–1.68) among current drinkers who never smoked compared with those who neither smoked nor drank. There was a significant interaction between smoking and drinking alcohol on MetS (P for interaction is 0.001).
Conclusions
Our study indicated that smoking and drinking is associated with higher prevalence of MetS. Interactions between smoking and drinking on the risk of MetS in men in China may also exist. Our findings need to be confirmed in future case-control or cohort studies.
doi:10.2188/jea.JE20130112
PMCID: PMC4150006  PMID: 24910131
cigarette smoking; alcohol consumption; metabolic syndrome; Chinese man; interaction
13.  Lung cancer, tobacco, and environmental factors in the African population of the Northern Province, South Africa 
Tobacco Control  1999;8(4):398-401.
DESIGN—Case-control study among incident African patients with cancer. Questionnaire assessment of exposure to tobacco, occupation, and place of birth.
SETTING—Northern Province, South Africa.
SUBJECTS—Between 1993 and 1995, 288 men and 60 women with lung cancer and 183 male and 197 female controls (consisting of patients newly diagnosed with cancers other than those known to be associated with smoking) were interviewed. Unmatched, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of developing lung cancer in relation to a number of variables.
MAIN OUTCOME MEASURE—Risk of developing lung cancer related to exposure to tobacco, indoor pollution, dusty work environment, and residential exposure to asbestos.
RESULTS—There was a significant increase in the risk of developing lung cancer through smoking. In men, the ORs were 2.2 (95% CI = 1.0 to 4.6) in ex-smokers, 9.8 (95% CI = 5.9 to 16.4) in light smokers (0-14 g/day), and 12.0 (95% CI = 6.5 to 22.3) in heavy smokers. In women, the ORs were 5.8 (95% CI = 1.3 to 25.8) in ex-smokers and 5.5 (95% CI = 2.6 to 11.3) in current smokers. Work in a dusty industry showed an elevated risk (OR = 3.2, 95% CI = 1.8 to 5.8) for lung cancer only in men. Male residents of areas where asbestos was shipped for distribution (termed moderately polluted asbestos areas) had a 2.5-fold increase (95% CI = 1.0 to 4.4) in the risk (OR) of developing lung cancer, and residents of areas where asbestos was mined (termed heavily polluted asbestos areas) had a 2.8-fold increase in risk (95% CI = 0.7 to 10.4). Female residents of heavily polluted asbestos areas showed elevated risks of 5.4 (95% CI = 1.3 to 22.5) of developing lung cancer.
CONCLUSION—The data suggest that tobacco smoking is the most important risk factor for the development of lung cancer in this setting. Risks for lung cancer are reminiscent of those observed in Western countries in the 1960s and 1970s. However, environmental exposure to asbestos, a dusty occupation (in men), and perhaps indoor air pollution may also contribute to the development of lung cancer in this province.


Keywords: lung cancer; tobacco smoking; South Africa
PMCID: PMC1759754  PMID: 10629246
14.  Combined Impact of Lifestyle-Related Factors on Total and Cause-Specific Mortality among Chinese Women: Prospective Cohort Study 
PLoS Medicine  2010;7(9):e1000339.
Findings from the Shanghai Women's Health Study confirm those derived from other, principally Western, cohorts regarding the combined impact of lifestyle-related factors on mortality.
Background
Although cigarette smoking, excessive alcohol drinking, obesity, and several other well-studied unhealthy lifestyle-related factors each have been linked to the risk of multiple chronic diseases and premature death, little is known about the combined impact on mortality outcomes, in particular among Chinese and other non-Western populations. The objective of this study was to quantify the overall impact of lifestyle-related factors beyond that of active cigarette smoking and alcohol consumption on all-cause and cause-specific mortality in Chinese women.
Methods and Findings
We used data from the Shanghai Women's Health Study, an ongoing population-based prospective cohort study in China. Participants included 71,243 women aged 40 to 70 years enrolled during 1996–2000 who never smoked or drank alcohol regularly. A healthy lifestyle score was created on the basis of five lifestyle-related factors shown to be independently associated with mortality outcomes (normal weight, lower waist-hip ratio, daily exercise, never exposed to spouse's smoking, higher daily fruit and vegetable intake). The score ranged from zero (least healthy) to five (most healthy) points. During an average follow-up of 9 years, 2,860 deaths occurred, including 775 from cardiovascular disease (CVD) and 1,351 from cancer. Adjusted hazard ratios for mortality decreased progressively with an increasing number of healthy lifestyle factors. Compared to women with a score of zero, hazard ratios (95% confidence intervals) for women with four to five factors were 0.57 (0.44–0.74) for total mortality, 0.29 (0.16–0.54) for CVD mortality, and 0.76 (0.54–1.06) for cancer mortality. The inverse association between the healthy lifestyle score and mortality was seen consistently regardless of chronic disease status at baseline. The population attributable risks for not having 4–5 healthy lifestyle factors were 33% for total deaths, 59% for CVD deaths, and 19% for cancer deaths.
Conclusions
In this first study, to our knowledge, to quantify the combined impact of lifestyle-related factors on mortality outcomes in Chinese women, a healthier lifestyle pattern—including being of normal weight, lower central adiposity, participation in physical activity, nonexposure to spousal smoking, and higher fruit and vegetable intake—was associated with reductions in total and cause-specific mortality among lifetime nonsmoking and nondrinking women, supporting the importance of overall lifestyle modification in disease prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
It is well established that lifestyle-related factors, such as limited physical activity, unhealthy diets, excessive alcohol consumption, and exposure to tobacco smoke are linked to an increased risk of many chronic diseases and premature death. However, few studies have investigated the combined impact of lifestyle-related factors and mortality outcomes, and most of such studies of combinations of established lifestyle factors and mortality have been conducted in the US and Western Europe. In addition, little is currently known about the combined impact on mortality of lifestyle factors beyond that of active smoking and alcohol consumption.
Why Was This Study Done?
Lifestyles in regions of the world can vary considerably. For example, many women in Asia do not actively smoke or regularly drink alcohol, which are important facts to note when considering practical disease prevention measures for these women. Therefore, it is important to study the combination of lifestyle factors appropriate to this population.
What Did the Researchers Do and Find?
The researchers used the Shanghai Women's Health Study, an ongoing prospective cohort study of almost 75,000 Chinese women aged 40–70 years, as the basis for their analysis. The Shanghai Women's Health Study has comprehensive baseline data on anthropometric measurements, lifestyle habits (including the responses to validated food frequency and physical activity questionnaires), medical history, occupational history, and select information from each participant's spouse, such as smoking history and alcohol consumption. This information was used by the researchers to create a healthy lifestyle score on the basis of five lifestyle-related factors shown to be independently associated with mortality outcomes in this population: normal weight, lower waist-hip ratio, daily exercise, never being exposed to spouse's smoking, and higher daily fruit and vegetable intake. The score ranged from zero (least healthy) to five (most healthy) points. The researchers found that higher healthy lifestyle scores were significantly associated with decreasing mortality and that this association persisted for all women regardless of their baseline comorbidities. So in effect, healthier lifestyle-related factors, including normal weight, lower waist-hip ratio, participation in exercise, never being exposed to spousal smoking, and higher daily fruit and vegetable intake, were significantly and independently associated with lower risk of total, and cause-specific, mortality.
What Do These Findings Mean?
This large prospective cohort study conducted among lifetime nonsmokers and nonalcohol drinkers shows that lifestyle factors, other than active smoking and alcohol consumption, have a major combined impact on total mortality on a scale comparable to the effect of smoking—the leading cause of death in most populations. However, the sample sizes for some cause-specific analyses were relatively small (despite the overall large sample size), and extended follow-up of this cohort will provide the opportunity to further evaluate the impact of these lifestyle-related factors on mortality outcomes in the future.
The findings of this study highlight the importance of overall lifestyle modification in disease prevention, especially as most of the lifestyle-related factors studied here may be improved by individual motivation to change unhealthy behaviors. Further research is needed to design appropriate interventions to increase these healthy lifestyle factors among Asian women.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000339
The Vanderbilt Epidemiology Center has more information on the Shanghai Women's Health Study
The World Health Organization provides information on health in China
The document Health policy and systems research in Chinacontains information about health policy and health systems research in China
The Chinese Ministry of Healthalso provides health information
doi:10.1371/journal.pmed.1000339
PMCID: PMC2939020  PMID: 20856900
15.  Active and involuntary tobacco smoking and upper-aerodigestive-tract cancer risks in a multicenter case-control study 
Introduction
Several important issues for the established association between tobacco smoking and upper-aerodigestive tract (UADT) cancer risks include the associations with smoking by cancer subsite, by type of tobacco, and among never alcohol drinkers, and the associations with involuntary smoking among nonsmokers. Our aim was to examine these specific issues in a large scale case-control study in Europe.
Methods
Analysis was performed on 2,103 UADT squamous cell carcinoma cases and 2,221 controls in the Alcohol-Related Cancers and Genetic Susceptibility in Europe (ARCAGE) project, a multicenter case-control study in 10 European countries. Unconditional logistic regression was performed to obtain odds ratios (OR) and 95% confidence intervals (CI).
Results
Compared to never tobacco smoking, current smoking was associated with UADT cancer risks (OR=6.72, 95% CI 5.45–8.30 for overall; 5.83, 4.50–7.54 for oral cavity and oropharynx; 12.19, 8.29–17.92 for hypopharynx and larynx; 4.17, 2.45–7.10 for esophagus). Among never drinkers, dose-response relationships with tobacco smoking packyears were observed for hypopharyngeal and laryngeal cancers (ptrend = 0.01), but not for oral cavity and oropharyngeal cancers (ptrend = 0.282). Among never smokers, ever exposure to involuntary smoking was associated with an increased risk of UADT cancers (OR=1.60, 95% CI 1.04–2.46).
Conclusion
Our results corroborate that tobacco smoking may play a stronger role in the development of hypopharyngeal and laryngeal cancers than that of oral cavity and oropharyngeal cancers among never drinkers and that involuntary smoking is an important risk factor for UADT cancers. Public health interventions to reduce involuntary smoking exposure could help reduce UADT cancer incidence.
doi:10.1158/1055-9965.EPI-09-0910
PMCID: PMC4085143  PMID: 19959682
Active tobacco smoking; involuntary smoking; upper-aerodigestive-tract cancer
16.  Alcohol and Tobacco Lower the Age of Presentation in Sporadic Pancreatic Cancer in a Dose-Dependent Manner: A Multicenter Study 
OBJECTIVES
The objective of this study was to examine the association between tobacco and alcohol dose and type and the age of onset of pancreatic adenocarcinoma (PancCa).
METHODS
Prospective data from the Pancreatic Cancer Collaborative Registry were used to examine the association between age of onset and variables of interest including: gender, race, birth country, educational status, family history of PancCa, diabetes status, and tobacco and alcohol use. Statistical analysis included logistic and linear regression, Cox proportional hazard regression, and time-to-event analysis.
RESULTS
The median age to diagnosis for PancCa was 66.3 years (95% confidence intervals (CIs), 64.5–68.0). Males were more likely than females to be smokers (77% vs. 69%, P = 0.0002) and heavy alcohol and beer consumers (19% vs. 6%, 34% vs. 19%, P < 0.0001). In univariate analysis for effects on PancCa presentation age, the following were significant: gender, alcohol and tobacco use (amount, status and type), family history of PancCa, and body mass index. Both alcohol and tobacco had dose-dependent effects. In multivariate analysis, alcohol status and dose were independently associated with increased risk for earlier PancCa onset with greatest risk occurring in heavy drinkers (HR 1.62, 95% CI 1.04–2.54). Smoking status had the highest risk for earlier onset pancreatic cancer with a HR of 2.69 (95% CI, 1.97–3.68) for active smokers and independent effects for dose (P = 0.019). The deleterious effects for alcohol and tobacco appear to resolve after 10 years of abstinence.
CONCLUSIONS
Alcohol and tobacco use are associated with a dose-related increased risk for earlier age of onset of PancCa. Although beer drinkers develop pancreatic cancer at an earlier age than nondrinkers, alcohol type did not have a significant effect after controlling for alcohol dose.
doi:10.1038/ajg.2012.288
PMCID: PMC3923585  PMID: 22929760
17.  Alcohol Consumption Among HIV-Infected Women: Impact on Time to Antiretroviral Therapy and Survival 
Journal of Women's Health  2011;20(2):279-286.
Abstract
Objective
Alcohol use is prevalent among HIV-infected people and is associated with lower antiretroviral adherence and high-risk sexual and injection behaviors. We sought to determine factors associated with alcohol use among HIV-infected women engaged in clinical care and if baseline alcohol use was associated with time to combination antiretroviral therapy (cART) and death in this population.
Methods
In an observational clinical cohort, alcohol consumption at the initial medical visit was examined and categorized as heavy, occasional, past, or no use. We used multinomial logistic regression to test preselected covariates and their association with baseline alcohol consumption. We then examined the association between alcohol use and time to cART and time to death using Kaplan-Meier statistics and Cox proportional hazards regression.
Results
Between 1997 and 2006, 1030 HIV-infected women enrolled in the cohort. Assessment of alcohol use revealed occasional and hazardous consumption in 29% and 17% of the cohort, respectively; 13% were past drinkers. In multivariate regression, heavy drinkers were more likely to be infected with hepatitis C than nondrinkers (relative risk ratios [RRR] 2.06, 95% confidence interval [CI] 1.29-3.44) and endorse current drug (RRR 3.51, 95% CI 2.09-5.91) and tobacco use (RRR 3.85 95% CI 1.81-8.19). Multivariable Cox regression adjusting for all clinical covariates demonstrated an increased mortality risk (hazard ratio [HR] 1.40, 95% CI 1.00-1.97, p < 0.05) among heavy drinkers compared to nondrinkers but no delays in cART initiation (1.04 95% CI 0.81-1.34)
Conclusions
Among this cohort of HIV-infected women, heavy alcohol consumption was independently associated with earlier death. Baseline factors associated with heavy alcohol use included tobacco use, hepatitis C, and illicit drug use. Alcohol is a modifiable risk factor for adverse HIV-related outcomes. Providers should consistently screen for alcohol consumption and refer HIV-infected women with heavy alcohol use for treatment.
doi:10.1089/jwh.2010.2043
PMCID: PMC3064875  PMID: 21281111
18.  Alcohol Consumption and Mortality in the Korean Multi-center Cancer Cohort Study 
Objectives
To examine the association between alcohol consumption habit, types of beverages, alcohol consumption quantity, and overall and cancer-specific mortality among Korean adults.
Methods
The alcohol consumption information of a total of 16 320 participants who were 20 years or older from the Korean Multi-center Cancer Cohort were analyzed to examine the association between alcohol consumption habit and mortality (median follow-up of 9.3 years). The Cox proportional hazard model was used to estimate the hazard ratio (HR) of alcohol consumption to mortality adjusting for age, sex, geographic areas, education, smoking status, and body mass index.
Results
Alcohol drinkers showed an increased risk for total mortality compared with never drinkers (HR, 1.72; 95% confidence interval [CI], 1.38 to 2.14 for past drinkers; HR, 1.21; 95% CI, 1.06 to 1.39 for current drinkers), while past drinkers only were associated with higher risk for cancer deaths (HR, 1.84; 95% CI, 1.34 to 2.53). The quantity of alcohol consumed per week showed a J-shaped association with risk of mortality. Relative to light drinkers (0.01 to 90 g/wk), never drinkers and heavy drinkers (>504 g/wk) had an increased risk for all-cause and cancer deaths: (HR, 1.18; 95% CI, 0.96 to 1.45) and (HR, 1.39; 95% CI, 1.05 to 1.83) for all-cause mortality; and (HR, 1.55; 95% CI, 1.15 to 2.11) and (HR, 2.07; 95% CI, 1.39 to 3.09) for all cancer mortality, respectively. Heavy drinkers (>504 g/wk) showed an elevated risk for death from stomach and liver cancers.
Conclusions
The present study supports the existence of a J-shaped association between alcohol consumption quantity and the risk of all-cause and cancer deaths. Heavy drinkers had an increased risk of death from cancer overall and liver and stomach cancer.
doi:10.3961/jpmph.2012.45.5.301
PMCID: PMC3469812  PMID: 23091655
Alcohol drinking; Mortality; Korean Multi-center Cancer Cohort; Korea
19.  Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged ≥45 Years in Asia: A Pooled Analysis of 21 Cohorts 
PLoS Medicine  2014;11(4):e1001631.
Wei Zheng and colleagues quantify the burden of tobacco-smoking-related deaths for adults in Asia.
Please see later in the article for the Editors' Summary
Background
Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest.
Methods and Findings
We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan—accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37–1.51) and 1.48-fold (1.38–1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%–17.2%) and 3.3% (2.6%–4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000–1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y.
Conclusions
Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, more than 5 million smokers die from tobacco-related diseases. Tobacco smoking is a major risk factor for cardiovascular disease (conditions that affect the heart and the circulation), respiratory disease (conditions that affect breathing), lung cancer, and several other types of cancer. All told, tobacco smoking kills up to half its users. The ongoing global “epidemic” of tobacco smoking and tobacco-related diseases initially affected people living in the US and other Western countries, where the prevalence of smoking (the proportion of the population that smokes) in men began to rise in the early 1900s, peaking in the 1960s. A similar epidemic occurred in women about 40 years later. Smoking-related deaths began to increase in the second half of the 20th century, and by the 1990s, tobacco smoking accounted for a third of all deaths and about half of cancer deaths among men in the US and other Western countries. More recently, increased awareness of the risks of smoking and the introduction of various tobacco control measures has led to a steady decline in tobacco use and in smoking-related diseases in many developed countries.
Why Was This Study Done?
Unfortunately, less well-developed tobacco control programs, inadequate public awareness of smoking risks, and tobacco company marketing have recently led to sharp increases in the prevalence of smoking in many low- and middle-income countries, particularly in Asia. More than 50% of men in many Asian countries are now smokers, about twice the prevalence in many Western countries, and more women in some Asian countries are smoking than previously. More than half of the world's billion smokers now live in Asia. However, little is known about the burden of tobacco-related mortality (deaths) in this region. In this study, the researchers quantify the risk of total and cause-specific mortality associated with tobacco use among adults aged 45 years or older by undertaking a pooled statistical analysis of data collected from 21 Asian cohorts (groups) about their smoking history and health.
What Did the Researchers Do and Find?
For their study, the researchers used data from more than 1 million participants enrolled in studies undertaken in Bangladesh, India, mainland China, Japan, the Republic of Korea, Singapore, and Taiwan (which together account for 71% of Asia's total population). Smoking prevalences among male and female participants were 65.1% and 7.1%, respectively. Compared with never-smokers, ever-smokers had a higher risk of death from any cause in pooled analyses of all the cohorts (adjusted hazard ratios [HRs] of 1.44 and 1.48 for men and women, respectively; an adjusted HR indicates how often an event occurs in one group compared to another group after adjustment for other characteristics that affect an individual's risk of the event). Compared with never smoking, ever smoking was associated with a higher risk of death due to cardiovascular disease, cancer (particularly lung cancer), and respiratory disease among Asian men and among East Asian women. Moreover, the researchers estimate that, in the countries included in this study, tobacco smoking accounted for 15.8% of all deaths among men and 3.3% of deaths among women in 2004—a total of about 1.5 million deaths, which scales up to 2 million deaths for the population of the whole of Asia. Notably, in 2004, tobacco smoking accounted for 60.5% of lung-cancer deaths among Asian men and 16.7% of lung-cancer deaths among East Asian women.
What Do These Findings Mean?
These findings provide strong evidence that tobacco smoking is associated with a substantially raised risk of death among adults aged 45 years or older throughout Asia. The association between smoking and mortality risk in Asia reported here is weaker than that previously reported for Western countries, possibly because widespread tobacco smoking started several decades later in most Asian countries than in Europe and North America and the deleterious effects of smoking take some years to become evident. The researchers note that certain limitations of their analysis are likely to affect the accuracy of its findings. For example, because no data were available to estimate the impact of secondhand smoke, the estimate of deaths attributable to smoking is likely to be an underestimate. However, the finding that nearly 45% of the global deaths from active tobacco smoking occur in Asia highlights the urgent need to implement comprehensive tobacco control programs in Asia to reduce the burden of tobacco-related disease.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001631.
The World Health Organization provides information about the dangers of tobacco (in several languages) and about the WHO Framework Convention on Tobacco Control, an international instrument for tobacco control that came into force in February 2005 and requires parties to implement a set of core tobacco control provisions including legislation to ban tobacco advertising and to increase tobacco taxes; its 2013 report on the global tobacco epidemic is available
The US Centers for Disease Control and Prevention provides detailed information about all aspects of smoking and tobacco use
The UK National Health Services Choices website provides information about the health risks associated with smoking
MedlinePlus has links to further information about the dangers of smoking (in English and Spanish)
SmokeFree, a website provided by the UK National Health Service, offers advice on quitting smoking and includes personal stories from people who have stopped smoking
Smokefree.gov, from the US National Cancer Institute, offers online tools and resources to help people quit smoking
doi:10.1371/journal.pmed.1001631
PMCID: PMC3995657  PMID: 24756146
20.  Lower Risk of Lung Cancer after Multiple Pneumonia Diagnoses 
Background
Although pneumonia has been suggested as a risk factor for lung cancer, previous studies have not evaluated the influence of number of pneumonia diagnoses in relation to lung cancer risk.
Methods
The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based study of 2,100 cases and 2,120 controls collected information on pneumonia more than one year before enrollment from 1,890 cases and 2,078 controls.
Results
After adjusting for study design variables, smoking, and chronic bronchitis, pneumonia was associated with decreased risk of lung cancer (odds ratio (OR), 0.79; 95% confidence interval (CI), 0.64–0.97), especially among individuals with ≥3 diagnoses versus none (OR, 0.35; 95% CI, 0.16–0.75). Adjustment for chronic bronchitis contributed to this inverse association. In comparison, pulmonary tuberculosis was not associated with lung cancer (OR, 0.96; 95% CI, 0.62–1.48).
Conclusions
The apparent protective effect of pneumonia among individuals with multiple pneumonia diagnoses may reflect an underlying difference in immune response and requires further investigation and confirmation.
Impact
Careful evaluation of number of pneumonia episodes may shed light on lung cancer etiology.
doi:10.1158/1055-9965.EPI-09-0873
PMCID: PMC2837523  PMID: 20200440
pneumonia; epidemiology; lung cancer; multiple infections; tuberculosis
21.  Moderate Alcohol Consumption is Protective Against Colorectal Adenomas in Smokers 
Digestive diseases and sciences  2007;53(1):116-122.
Background
Although some studies have shown an association between alcohol consumption and colorectal adenomas, the effect of moderate alcohol consumption is not well-defined, nor is the interaction between alcohol and smoking.
Aim
To investigate the relationship between different levels of alcohol consumption and colorectal adenomas and to determine whether smoking modifies this relationship.
Methods
Eligible patients who underwent a complete colonoscopy were included (179 cases and 466 controls). Alcohol consumption was obtained from a lifestyle questionnaire. Patients were divided into three groups: 1) Abstainers: 0 drinks/week; 2) Moderate drinkers: >0-<7 drinks/week; 3) Heavy drinkers: >=7 drinks/week. Odds ratios (OR) were calculated using logistic regression, controlling for gender, age, body mass index, use of non-steroidal anti-inflammatory medications. Results were stratified by the number of years smoked.
Results
The proportion of patients with adenomas was 29.6% in abstainers, 22.1% in moderate drinkers, and 36.7% in heavy drinkers. There was significant modification of the relationship between alcohol consumption and colorectal adenomas by smoking. For individuals who had never smoked, heavy drinkers were at significantly increased odds of having an adenoma compared to moderate drinkers (OR 3.08; 95% CI: 1.50-6.32), while no difference was seen for abstainers (OR 0.99; 95% CI: 0.52-1.89). Similarly, among individuals who had smoked 1-14 years, heavy drinkers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.61; 95% CI: 1.04-6.51), and no difference was seen for abstainers (OR 1.02; 95% CI: 0.33-3.10). Somewhat unexpectedly, among individuals who had smoked for 15 or more years, abstainers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.04; 95% CI: 0.91-4.59), while heavy drinkers were not at increased odds of having an adenoma (OR 0.73; 95% CI: 0.27-1.97).
Conclusions
Consumption of less than seven alcohol drinks per week does not increase the risk of having a colorectal adenoma. We found evidence in this study that moderate alcohol consumption among long-term smokers may potentially decrease the risk of an adenoma compared to abstainers.
doi:10.1007/s10620-007-9831-3
PMCID: PMC2664311  PMID: 17510802
22.  Effect of different types of smoking and synergism with Hepatitis C virus on risk of hepatocellular carcinoma in American men and women: Case-control study 
The International Agency for Research on Cancer has declared smoking to be a risk factor for hepatocellular carcinoma (HCC). However, passive exposure to cigarette smoke and use of noncigarette tobacco products on the risk of HCC has not been examined. Therefore, we evaluated the independent effects of different types of smoking exposure along with multiple risk factors for HCC and determined whether the magnitude of smoking was modified by other risk factors in men and women. We conducted a case-control study at The University of Texas M. D. Anderson Cancer Center where 319 HCC patients and 1,061 healthy control subjects were personally interviewed for several HCC risk factors. Multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for each potential risk factor. Use of smokeless tobacco (chewing tobacco and snuff), cigars, pipes and passive smoking exposure were not related to HCC among noncigarette smokers. However, regular cigarette smoking was associated with HCC in men: AOR, 1.9 (95% CI, 1.1–3.1). Heavy alcohol consumption was associated with HCC in women: AOR, 7.7 (95% CI, 2.3–25.1). Cigarette smoking interacted synergistically with chronic infection of hepatitis C virus in men: AOR, 136.3 (95% CI, 43.2–429.6) and with heavy alcohol consumption in women: AOR, 13.7 (95% CI, 3.2–57.9). We conclude that sex differences were observed in HCC relationship with cigarette smoking and alcohol consumption. Controlling for smoking exposure might be a prudent approach to the prevention of HCC, especially in patients with chronic viral hepatitis infections.
doi:10.1002/ijc.23730
PMCID: PMC2673571  PMID: 18688864
passive smoking; HCC; cigarette smoking; gender; pipes; cigars; tobacco
23.  Risk factors for oesophageal, lung, oral and laryngeal cancers in black South Africans 
British Journal of Cancer  2002;86(11):1751-1756.
The authors used data collected from 1995 to 1999, from an on-going cancer case–control study in greater Johannesburg, to estimate the importance of tobacco and alcohol consumption and other suspected risk factors with respect to cancer of the oesophagus (267 men and 138 women), lung (105 men and 41 women), oral cavity (87 men and 37 women), and larynx (51 men). Cancers not associated with tobacco or alcohol consumption were used as controls (804 men and 1370 women). Tobacco smoking was found to be the major risk factor for all of these cancers with odds ratios ranging from 2.6 (95% CI 1.5–4.5) for oesophageal cancer in female ex-smokers to 50.9 (95% CI 12.6–204.6) for lung cancer in women, and 23.9 (95% CI 9.5–60.3) for lung cancer and 23.6 (95% CI 4.6–121.2) for laryngeal cancer in men who smoked 15 or more grams of tobacco a day. This is the first time an association between smoking and oral and laryngeal cancers has been shown in sub-Saharan Africa. Long-term residence in the Transkei region in the southeast of the country continues to be a risk factor for oesophageal cancer, especially in women (odds ratio=14.7, 95% CI 4.7–46.0), possibly due to nutritional factors. There was a slight increase in lung cancer (odds ratio=2.9, 95% CI 1.1–7.5) in men working in ‘potentially noxious’ industries. ‘Frequent’ alcohol consumption, on its own, caused a marginally elevated risk for oesophageal cancer (odds ratio=1.7, 95% CI 1.0–2.9, for women and odds ratio=1.8, 95% CI 1.2–2.8, for men). The risks for oesophageal cancer in relation to alcohol consumption increased significantly in male and female smokers (odds ratio=4.7, 95% CI=2.8–7.9 in males and odds ratio=4.8, 95% CI 3.2–6.1 in females). The above results are broadly in line with international findings.
British Journal of Cancer (2002) 86, 1751–1756. doi:10.1038/sj.bjc.6600338 www.bjcancer.com
© 2002 Cancer Research UK
doi:10.1038/sj.bjc.6600338
PMCID: PMC2375408  PMID: 12087462
epidemiology; case–control; oesophagus; lung; oral; larynx
24.  Cigarettes and alcohol in relation to colorectal cancer: the Singapore Chinese Health Study 
British Journal of Cancer  2007;96(5):821-827.
The relations were examined between colorectal cancer and cigarette smoking and alcohol consumption within the Singapore Chinese Health Study, a population-based, prospective cohort of 63 257 middle-aged and older Chinese men and women enrolled between 1993 and 1998, from whom baseline data on cigarette smoking and alcohol consumption were collected through in-person interviews. By 31 December 2004, 845 cohort participants had developed colorectal cancer (516 colon cancer, 329 rectal cancer). Compared with nondrinkers, subjects who drank seven or more alcoholic drinks per week had a statistically significant, 72% increase in risk of colorectal cancer hazard ratio (HR)=1.72; 95% confidence interval (CI)=1.33–2.22). Cigarette smoking was associated with an increased risk of rectal cancer only. Compared with nonsmokers, HRs (95% CIs) for rectal cancer were 1.43 (1.10–1.87) for light smokers and 2.64 (1.77–3.96) for heavy smokers. Our data indicate that cigarette smoking and alcohol use interact in the Chinese population in an additive manner in affecting risk of rectal cancer, thus suggesting that these two exposures may share a common etiologic pathway in rectal carcinogenesis.
doi:10.1038/sj.bjc.6603623
PMCID: PMC2360085  PMID: 17311023
cigarette smoking; alcohol drinking; colorectal cancer; Singapore Chinese
25.  Alcohol, Tobacco and Diet in Relation to Esophageal Cancer: The Shanghai Cohort Study 
Nutrition and cancer  2008;60(3):354-363.
Prospective data on environmental exposures, especially with respect to alcohol, tobacco and diet, in relation to the risk of esophageal cancer in high risk populations are sparse. We analyzed data from a population-based cohort of 18 244 middle-aged and older men in Shanghai to identify risk factors for esophageal cancer in this high-risk population. The cohort was followed through 2006 and 101 incident esophageal cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and their corresponding 95% confidence intervals (CI) for associations between exposures and esophageal cancer risk. With adjustment for tobacco use and other potential confounders, regular drinkers versus nondrinkers of alcoholic beverages had a 2-fold risk of developing esophageal cancer (HR = 2.02, 95% CI = 1.31–3.12). With adjustment for alcohol and other potential confounders, long-term smokers (40+ years) versus nonsmokers of cigarettes showed a 2-fold risk of developing esophageal cancer (HR=2.06, 95% CI=1.11–3.82). Increased consumption of fruits (including oranges/tangerines), seafood and milk were found to be protective against the development of esophageal cancer; HRs were decreased by 40%–60% for high versus low consumers after adjustment for cigarette smoking, alcohol drinking and other confounders.
doi:10.1080/01635580701883011
PMCID: PMC2409004  PMID: 18444169
alcohol; tobacco; diet; esophageal cancer; Chinese

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