The short- and long-term effects of pregnancy on breast cancer risk are well documented. Insight into potential biological mechanisms for these associations may be gained by studying breast cancer risk and pregnancy characteristics (e.g., preeclampsia, twining), which may reflect hormone levels during pregnancy. To date, no review has synthesized the published literature for pregnancy characteristics and maternal breast cancer using systematic search methods. We conducted a systematic search to identify all published studies. Using PUBMED (to 31 July 2009), 42 relevant articles were identified. Several studies suggest that multiple births may be associated with a lowered breast cancer risk of about 10–30%, but results were inconsistent across 18 studies. The majority of 13 studies suggest about a 20–30% reduction in risk with preeclampsia and/or gestational hypertension. Six of seven studies reported no association for infant sex and breast cancer risk. Data are sparse and conflicting for other pregnancy characteristics such as gestational age, fetal growth, pregnancy weight gain, gestational diabetes, and placental abnormalities. The most consistent findings in a generally sparse literature are that multiple births and preeclampsia may modestly reduce breast cancer risk. Additional research is needed to elucidate associations between pregnancy characteristics, related hormonal profiles, and breast cancer risk.
Breast cancer; Pregnancy; Perinatal; Epidemiology
Metabolic syndrome (MetS) is an established risk factor for cardiovascular diseases and mortality. Limited data are available on the prevalence of MetS and its association with exercise among breast cancer survivors. The present study included 1696 breast cancer survivors from the Shanghai Breast Cancer Survival Study, a population-based prospective cohort study conducted between April 2002 and October 2011 in Shanghai, China. All women had a physical examination taken at study clinic approximately 60 months post-diagnosis. Exercise was assessed at approximately 6, 18, 36, and 60 months post-diagnosis. Information on medical history, tumor characteristics, cancer treatment, anthropometrics, and lifestyle were collected at study enrollment. Associations between exercise and MetS at 60 months post-diagnosis were evaluated with multivariable logistic regression models. The mean age of the study population was 56.68 at 60-month survey and the mean follow-up since cancer diagnosis was 63.66 months. The prevalence of MetS using NCEP-ATPIII criteria at approximately 60 months after diagnosis was 33.14%. Among overweight and obesity breast cancer survivors (BMI≥25 kg/m2 at baseline), the prevalence was 55.18%. The most common type of exercise in this population was walking (45.40%) at baseline. Exercise participation between 6 and 60 months post-diagnosis was inversely associated with the prevalence of MetS with the adjusted OR for exercise participation of ≥3.5 hours/week (30 minutes/day) being 0.69 (95% CI: 0. 0.48–0.98). In addition consistent exercise participation reduced the prevalence of MetS (adjusted OR 0.70 (95%CI: 0.50–1.00). Associations of exercise with MetS were not modified by baseline WC, BMI, comorbidity, baseline menopausal status, TNM stage, cancer treatment, or ER/PR status (P interactions >0.05). Regular and persistent exercise after cancer diagnosis, even at low-to-moderate intensity level, decrease the prevalence of MetS among long-term breast cancer survivors.
Breast cancer; Metabolic Syndrome; Exercise; Survivorship
Evidence implicating hyperinsulinemia and insulin resistance in the etiology of colorectal cancer suggests that a diet characterized by a high glycemic index and load may increase the risk of this disease, but previous studies have yielded inconsistent results. We assessed the association between intake of total carbohydrates, sugars, fiber, and the glycemic index (GI) and glycemic load (GL) of individual diets, and risk of developing colorectal cancer among 158,800 participants in the Women’s Health Initiative (WHI). We used a GI/GL database developed specifically for the WHI food-frequency questionnaire. Over an average of 7.8 years of follow-up, 1,476 incident cases of colorectal cancer were identified. Cox proportional hazards models were used to estimate the association between dietary factors classified by quintiles and risk of colorectal cancer, with adjustment for covariates. Total carbohydrate intake, glycemic index, glycemic load, and intake of sugars and fiber showed no association with colorectal cancer. Analyses by cancer subsite yielded null results, with the exception of a borderline positive association between glycemic load and rectal cancer (HR for the highest vs. lowest quintile 1.84, 95% confidence interval 0.95–3.56, p for trend 0.05). Analyses stratified by tertiles of body mass index and physical activity showed no evidence of effect modification by these factors. Results of this large study do not support of a role of a diet characterized by a high glycemic index or load in colorectal carcinogenesis in postmenopausal women.
To investigate the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) lower lung cancer risk.
We analysed pooled individual-level data from seven case–control and one cohort study in the International Lung Cancer Consortium (ILCCO). Relative risks for lung cancer associated with self-reported history of aspirin and other NSAID use were estimated within individual studies using logistic regression or proportional hazards models, adjusted for packyears of smoking, age, calendar period, ethnicity and education and were combined using random effects meta-analysis.
A total of 4,309 lung cancer cases (mean age at diagnosis 65 years, 45% adenocarcinoma and 22% squamous-cell carcinoma) and 58,301 non-cases/controls were included. Amongst controls, 34% had used NSAIDs in the past (81% of them used aspirin). After adjustment for negative confounding by smoking, ever-NSAID use (affirmative answer to the study-specific question on NSAID use) was associated with a 26% reduction (95% confidence interval 8 to 41%) in lung cancer risk in men, but not in women (3% increase (−11% to 30%)). In men, the association was stronger in current and former smokers, and for squamous-cell carcinoma than for adenocarcinomas, but there was no trend with duration of use. No differences were found in the effects on lung cancer risk of aspirin and non-aspirin NSAIDs.
Evidence from ILCCO suggests that NSAID use in men confers a modest protection for lung cancer, especially amongst ever-smokers. Additional investigation is needed regarding the possible effects of age, duration, dose and type of NSAID and whether effect modification by smoking status or sex exists.
NSAIDs; Aspirin; Lung cancer
Contrary to the hypothesis that the racial/ethnic disparity in prostate cancer has a hormonal basis, we did not observe a difference in serum testosterone concentration between non-Hispanic black and white men in the Third National Health and Nutrition Examination Survey (NHANES III), although non-Hispanic black men had a higher estradiol level. Unexpectedly, Mexican-American men had the highest testosterone level. Next, we evaluated whether the same patterns are observed during adolescence, the time of prostate maturation.
We measured serum testosterone, estradiol, and sex hormone binding globulin (SHBG) by immunoassay in 134 males aged 12–19 in NHANES III. Mean concentrations were compared by race/ethnicity adjusting for age, Tanner stage, percent body fat, waist, physical activity, tobacco smoke, and the other hormones.
After multivariable adjustment, in the 12–15 year-old males, testosterone concentration was lower in non-Hispanic blacks than whites (P=0.043), SHBG concentration did not significantly differ between the two groups. Mexican-Americans had the highest testosterone (versus non-Hispanic black: P=0.002) and lowest SHBG (versus non-Hispanic white: P=0.010; versus non-Hispanic black: P=0.047) concentrations. Estradiol concentration was lower in non-Hispanic blacks (P=0.11) and Mexican-Americans (P=0.033) compared with non-Hispanic whites. After multivariable adjustment, in the 16–19 year-old males, testosterone, estradiol, and SHBG concentrations did not differ between non-Hispanic blacks and whites. Mexican-Americans had the highest testosterone concentration (versus non-Hispanic white: P=0.08), but did not differ from the other groups on estradiol and SHBG concentrations. In both age groups, these patterns were generally present, but less pronounced after adjusting for age and Tanner stage only.
In adolescent males, non-Hispanic blacks did not have a higher testosterone concentration than non-Hispanic whites, and Mexican-Americans had the highest testosterone concentration, patterns similar to adult males.
testosterone; adolescence; race and ethnicity
Obesity has been consistently associated with increased risk of pancreatic cancer incidence and mortality. However, studies of obesity and overall survival in patients with pancreatic cancer are notably lacking, especially in population-based studies.
Active and passive follow-up were used to determine vital status and survival for 510 pancreatic cancer patients diagnosed from 1995–1999 in a large population-based case-control study in the San Francisco Bay Area. Survival rates were computed using Kaplan-Meier methods. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated in multivariable Cox proportional hazards models as measures of the association between pre-diagnostic obesity and pancreatic cancer survival.
An elevated hazard ratio of 1.3 (95% CI, 0.91–1.81) was observed for obese (body mass index [BMI] ≥30) compared with normal range BMI (<25) patients. Associations between overall survival and known pancreatic cancer prognostic and risk factors did not significantly vary by BMI (all P-interaction ≥0.18), yet elevated HRs consistently were observed for obese compared with normal BMI patients [localized disease at diagnosis (HR, 3.1), surgical resection (HR, 1.6), ever smokers (HR, 1.6), diabetics (HR, 3.3)]. Poor survival was observed among men, older patients, more recent and current smokers, whereas improved survival was observed for Asian/Pacific Islanders.
Our results in general provide limited support for an association between prediagnostic obesity and decreased survival in patients with pancreatic cancer. Patterns of reduced survival associated with obesity in some patient subgroups could be due to chance and require assessment in larger pooled studies.
Pancreatic cancer; obesity; survival; population-based cohort
A history of allergies is associated with a decreased risk of several types of cancers. Potential mechanisms include enhanced immune surveillance against tumor cells early in disease development and/or carcinogenic infectious agents. We tested whether allergies are inversely associated with oral squamous cell carcinoma (OSCC), accounting for factors that may modify the association, such as tumor site, stage, and HPV infection.
We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between allergy history (including different types of allergies) and OSCC, adjusted for potential confounders, among 400 cases and 613 controls. Analyses were also stratified by site, stage, and measures of HPV infection.
We observed a weak inverse association between history of any allergy and OSCC (OR=0.81, 95% CI, 0.61–1.08). This association was present only for allergies to airborne allergens (dust/pollen/mold); OR=0.67; 95% CI, 0.48–0.93. The inverse associations with airborne allergies were slightly stronger for oropharyngeal SCC (OR=0.56; 95% CI, 0.35–0.90) than for oral cavity SCC (OR=0.71; 95% CI, 0.49–1.05), and present only for later stage cancers (OR=0.42; 95% CI, 0.26–0.66) as opposed to earlier stage cancers (OR=0.98; 95% CI, 0.66–1.46). Inverse associations were not particularly present or stronger among HPV-16 seropositive individuals or for HPV DNA positive OSCC.
There is an inverse association between history of allergies to dust, pollen or mold and OSCC. Whether the inverse association involves heightened immune surveillance, increased immune response to HPV or other antigen, or other carcinogenic mechanism, remains to be determined in more definitive studies.
allergies; oral squamous cell carcinoma; HPV; HSV
B vitamins and methionine have been postulated to have potential effects on carcinogenesis; however, findings from previous epidemiologic studies on B vitamins, methionine, and lung cancer risk are inconsistent. We investigated associations of dietary intakes of B vitamins (i.e., riboflavin, niacin, vitamin B6, folate, and vitamin B12) and methionine with lung cancer risk among female never smokers.
The Shanghai Women’s Health Study, a population-based, prospective cohort study, included 74,941 women. During a median follow-up of 11.2 years, 428 incident lung cancer cases accrued among 71,267 women with no history of smoking or cancer at baseline. Baseline dietary intakes were derived from a validated, interviewer-administered food frequency questionnaire. Cancer incidence and vital status were ascertained through annual linkage to the Shanghai Cancer Registry and Shanghai Vital Statistics Registry databases and through biennial in-person follow-ups with participants. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression.
Dietary riboflavin intake was inversely associated with lung cancer risk (HR = 0.62; 95% CI = 0.43–0.89; P-trend = 0.03 for the highest quartile compared with the lowest). A higher than median intake of methionine was associated with lower risk of lung cancer (HR = 0.78; 95% CI = 0.60–0.99), however, there was no dose-response relation. Intakes of other B vitamins were not associated with lung cancer risk.
Our study suggests that dietary riboflavin intake may be inversely associated with lung cancer risk among female never smokers, which warrants further investigation.
B vitamins; methionine; lung cancer; never smokers; women
Background and purpose
Previous studies have shown that physical inactivity and obesity are risk factors for the development of colorectal cancer. However, controversy exists regarding the influence of these factors on survival in colorectal cancer patients. We evaluated the impact of recreational physical activity and body mass index (BMI) before and after colorectal cancer diagnosis on disease-specific mortality and all-cause mortality.
Patients and Methods
This prospective cohort study included 1339 women enrolled in the Women’s Health Initiative study who were diagnosed with colorectal cancer subsequent to study enrolment. BMI and recreational physical activity were measured before cancer diagnosis at study entry (pre-diagnostic) and after diagnosis at study follow-up interviews (post-diagnostic). We used Cox regression to estimate the association between pre- and post-diagnostic exposures and survival after colorectal cancer diagnosis.
Among women diagnosed with colorectal cancer, 265 (13%) deaths occurred during a median study follow-up of 11.9 years, of which 171 (65%) were attributed to colorectal cancer. Compared with women reporting no pre-diagnostic recreational physical activity, those reporting activity levels of ≥18 MET-hours/week had significantly lower colorectal cancer-specific mortality (hazard ratio (HR)=0.68; 95% confidence interval (CI): 0.41–1.13) and all-cause mortality (HR=0.63; 95% CI: 0.42–0.96). Similar inverse associations were seen for post-diagnostic recreational physical activity. Neither pre- nor post-diagnostic BMI were associated with mortality after colorectal cancer diagnosis.
Recreational physical activity before and after CR colorectal cancer C diagnosis, but not BMI, is associated with more favourable survival.
Physical activity; body mass index; colorectal cancer; survival; postmenopausal
Associations between sun exposure (a primary source of Vitamin D) and risk of ovarian cancer have been inconsistent. Furthermore, studies have not investigated whether sun exposure at different periods in the lifetime of a person results in differences in risk associations, and little is known about differences according to histological subtype.
Using a population-based case-control study of 1,334 non-Hispanic white women diagnosed with epithelial ovarian cancer in western Washington State between 2002–2009 and 1,679 non-Hispanic white controls, we assessed the relation of epithelial ovarian cancer with constitutional pigmentation characteristics, sun exposure behaviors, and an index of ultraviolet (UV) exposure based on residential history. Information was collected through in-person interviews. Logistic regression was used to compute odds ratios, 95% confidence intervals and trend P values (Ptrend).
We noted no association with residence-based measures of UV exposure or self-reported sun exposure, either over the lifetime or within specific age intervals. Also, we observed little evidence of association between constitutional pigmentation characteristics and risk, save for a suggestion of increased risk among women who reported increased ability to suntan upon prolonged sun exposure (Ptrend= 0.03).
Results from this study suggest that sun exposure has little influence on the risk of epithelial ovarian cancer. Additional studies in populations with a wider gradient of sun exposure may yet be warranted.
Ovarian cancer; sun exposure; histology; epidemiology
To evaluate the association of body size – captured via whole body dual-energy x-ray absorptiometry (DXA) and physical measurement – with serum sex steroid hormones and sex hormone binding globulin (SHBG) we utilized cross-sectional data and serum samples from the National Health and Nutrition Examination Survey (NHANES; 1999-2004).
Testosterone, androstanediol glucuronide (3-alpha-diol-G), estradiol and SHBG were measured via immunoassay in serum samples from a total of 898 adult men (ages 20-90) participating in the morning examination. As part of the NHANES data collection DXA scans and measurements of weight, height and waist circumference were performed by trained staff. Linear regression was used to estimate associations between body size and hormone levels adjusted for potential confounders and NHANES sampling procedures.
Total bone area (cm2) was inversely associated with total testosterone (ng/mL) [beta=-0.12; p-value<0.01], while bone mineral density (g/cm2) was inversely associated with SHBG (nmol/L) [beta=-17.16; p-value=0.01]. Increased percent body fat was associated with lower concentrations of total testosterone [beta=-0.16; p-value<0.01] and SHBG [beta=-1.11; p-value<0.01] and higher concentrations of free estradiol (fg/mL) [beta=12.52; p-value<0.01].
Clinical measures of body fat (measured via DXA scan) and anthropometric measures of body fat (BMI and waist circumference) provided similar inferences regarding the association between increased body fat and hormone levels in men. Increased body fat was associated with lower circulating levels of testosterone (total and free) and SHBG and higher circulating levels of free estradiol in men, while decreased bone mineral density was associated with higher circulating levels of SHBG.
dual-energy X-ray absorptiometry; DXA; estradiol; testosterone; androstanediol glucuronide; sex hormone binding globulin; National Health and Nutrition Examination Survey; NHANES; men
Absent gold standard diagnoses, we estimate age-specific false-positive and false-negative prediction rates of HPV-, cytology- and histology-based tests for significant cervical lesions (SCL) in U.S. women with AGC-NOS Pap smear diagnoses.
Modified Latent Class Model (LCM) analyses, with prevalence of SCL modeled as a function of age, were applied to GOG-0171 study data (n=122). The accuracies of several HPV-based tests, including Hybrid Capture II high-risk HPV (HC2 H-HPV); carbonic anhydrase IX (CA-IX) and invasive histological diagnosis were compared. 1-PPV and 1-NPV were written as functions of sensitivity, specificity and prevalence to obtain age-specific false-positive and false-negative rates.
The histology-based test was nearly perfect (sensitivity=1.00, CI=0.98-1.00; specificity=0.99, CI=0.96-1.00). Otherwise, HC2 H-HPV performed best (sensitivity=1.00, CI=1.00-1.00; specificity=0.87, CI=0.79-0.94). The false-positive detection rates (1-PPV) for HC2 H-HPV were high (>17%) at each age, while those of the histological diagnoses were low (<5% at ages≤60 and <17% overall ages). False negative prediction rates (1-NPV) for HC2 H-HPV were < 0.11% at each age and were uniformly lower than those of other tests, including the histology-based test (<0.25%). CA-IX together with HC2 H-HPV did not improve performance.
Women with negative HC2 H-HPV can safely forego invasive treatment (i.e., cone or LEEP biopsy, hysterectomy) in favor of observational follow-up. Additional biomarkers must be found for use in combination with HC2 H-HPV to reduce false-positive rates. This novel application of a modified Latent Class Model (LCM) exemplifies methods for potential use in future cancer screening studies when gold standard diagnoses are not available.
The mechanisms driving the physical activity–breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity–breast cancer association.
We investigated the main and joint effects of three previously unreported polymorphisms in CAT on breast cancer risk. We also estimated interactions between recreational physical activity (RPA) and 13 polymorphisms in oxidative stress-related genes. Data were from the Long Island Breast Cancer Study Project, with interview and biomarker data available on 1,053 cases and 1,102 controls.
Women with ≥1 variant allele in CAT rs4756146 had a 23 % reduced risk of postmenopausal breast cancer compared with women with the common TT genotype (OR = 0.77; 95 % CI = 0.59–0.99). We observed two statistical interactions between RPA and genes in the anti-oxidant pathway (p = 0.043 and 0.006 for CAT and GSTP1, respectively). Highly active women harboring variant alleles in CAT rs1001179 were at increased risk of breast cancer compared with women with the common CC genotype (OR = 1.61; 95 % CI, 1.06–2.45). Risk reductions were observed among moderately active women carrying variant alleles in GSTP1 compared with women homozygous for the major allele (OR = 0.56; 95 % CI, 0.38–0.84).
Breast cancer risk may be jointly influenced by RPA and genes involved in the antioxidant pathway, but our findings require confirmation.
Breast cancer; Epidemiology; Catalase; Physical activity; Oxidative stress
Epidemiologic studies have yet to provide consistent evidence to support a protective effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAID) on the incidence of breast cancer.
We evaluated the relations of current use of aspirin, non-aspirin NSAIDs, and acetaminophen with breast cancer incidence in the Black Women's Health Study.
Biennial follow-up of 59,000 study participants began in 1995. During 558,600 person years of follow-up through 2007, 1,275 breast cancer cases were identified. Using Cox proportional hazards regression, we estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) for associations of current and former use of aspirin, other NSAIDs, and acetaminophen with incident breast cancer.
After adjustment for age, education, body mass index at age 18, physical activity, female hormone use, current smoking, and other NSAID use, the IRRs were 0.79 (95%CI=0.66, 0.95) for current aspirin use and 0.68 (95%CI=0.50, 0.92) for ≥ 5 years of aspirin use. Similar associations were observed for acetaminophen use.
Both aspirin and acetaminophen use were inversely associated with breast cancer incidence in the present study. Reasons for the association with acetaminophen use are unclear, given that acetaminophen has very weak anti-inflammatory effects.
Aspirin; NSAIDs; breast cancer; incidence; epidemiology
Few studies have investigated the association between breast density and breast cancer by a family history of breast cancer, menopausal status and postmenopausal hormone use (PMH). We investigated if associations of breast density and breast cancer differ according to the status of these risk factors.
This study included 1,481 incident breast cancer cases diagnosed within the Nurses’ Health Study I and II cohorts and 2,779 matched controls. Breast density was measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from the biennial questionnaires before the date of the cancer diagnosis for cancer cases and their matched controls. The data were analyzed with logistic regression.
Breast cancer risk increased with increasing percent breast density in all strata (p for trend in all subsets<0.0001). The density-related risk of breast cancer was similar in women with and without a family history (OR=4.00 [95% CI 2.01–7.94] vs. 3.71 [95% CI 2.79–4.94] for density ≥50% vs. <10%, p for interaction=0.53). The magnitude of the association between density and breast cancer risk, however, appeared to be stronger in premenopausal women than in postmenopausal women without PMH history (OR=5.49 [95% CI 2.44–12.39] vs. 3.02 [95% CI1.62–5.63] for density ≥50% vs. <10%, p-heterogeneity=0.17) and appeared to be stronger in postmenopausal women currently using hormones compared to postmenopausal women who never used PMH (OR=4.50 [95% CI 2.99–6.78] vs. 3.02, p-heterogeneity=0.20) or with past hormone use (OR=4.50 vs. 3.71 [95% CI 1.90–7.23], p-heterogeneity=0.23).
Findings on associations by menopausal status/hormone use are suggestive and should be examined in additional larger studies.
breast density; breast cancer risk; family history of breast cancer; postmenopausal hormone use; menopausal status
Tea and coffee contain bioactive compounds and both beverages have recently been associated with a reduced risk of prostate cancer (PCa).
We studied associations of tea and coffee consumption with PCa risk in a population-based case-control study from King County, Washington, US. Prostate cancer cases were diagnosed in 2002-2005 and matched to controls by five-year age groups. Logistic regression was used to generate odds ratios (ORs) and 95% confidence intervals (CIs).
Among controls, 19% and 58% consumed at least one cup per day of tea and coffee, respectively. The analysis of tea included 892 cases and 863 controls and tea consumption was associated with a reduced overall PCa risk with an adjusted OR of 0.63 (95% CI: 0.45, 0.90; P for trend = 0.02) for men in the highest compared to lowest category of tea intake (≥2 cups/day versus ≤1 cup/week). Risk estimates did not vary substantially by Gleason grade or disease stage. Coffee consumption was not associated with risk of overall PCa or PCa in subgroups defined by tumor grade or stage.
Our results contribute further evidence that tea consumption may be a modifiable exposure that reduces PCa risk.
prostate cancer; tea; coffee; risk; stage; Gleason grade
Obesity is associated with a variety of chronic diseases, including cancer, which may partly be explained by its influence on sex steroid hormone concentrations. Whether different measures of obesity, i.e., body mass index (BMI), waist circumference, and percent body fat were differentially associated with circulating levels of sex steroid hormones was examined in 1,265 men, aged 20 to 90+ years, attending the morning examination session of the Third National Health and Nutrition Examination Survey (NHANES III).
Methods and Methods
Serum hormones were measured by immunoassay. Weight, height, and waist circumference were measured by trained staff. Percent body fat was estimated from bioelectrical impedance. Multivariate linear regression was used to estimate associations between body fatness measures and hormone levels.
Total and free testosterone and sex hormone binding globulin concentrations decreased, whereas total and free estradiol increased with increasing BMI, waist circumference, and percent body fat (all P-trend <0.05). The magnitude of change in these hormones was similar for a one quartile increase in each body fatness measure.
Measured BMI, waist circumference, and percent body fat led to similar inferences about their association with hormone levels in men.
NHANES III; testosterone; estradiol; obesity
Insulin and glucose may influence cancer mortality via their proliferative and anti-apoptotic properties. Using longitudinal data from the nationally representative Third National Health and Nutrition Examination Survey (NHANES III;1988–1994), with an average follow-up of 8.5y to mortality, we evaluated markers of glucose and insulin concentrations, with cancer mortality, ascertained using death certificates using the National Death Index. Plasma glucose, insulin, C-peptide, and lipid concentrations were measured. Anthropometrics, lifestyle, medical and demographic information was obtained during in-person interviews. After adjusting for age, race, sex, smoking status, physical activity and body mass index, for every increase in 50 mg/dl of plasma glucose, there was a 22% increased risk of overall cancer mortality. Insulin resistance was associated with a 41% (95% confidence interval (CI)(1.07–1.87;p=0.01) increased risk of overall cancer mortality. These associations were stronger after excluding lung cancer deaths for insulin resistant individuals (HR:1.67; 95% CI:1.15–2.42;p=0.01), specifically among those with lower levels of physical activity (HR:2.06; 95% CI:1.4–3.0;p=0.0001). Similar associations were observed for other blood markers of glucose and insulin, albeit not statistically significant. In conclusions, hyperglycemia and insulin resistance may be ‘high-risk’ conditions for cancer mortality. Managing these conditions may be effective cancer control tools.
cancer mortality; insulin; glucose control; epidemiology; longitudinal study
It has been widely accepted that sun exposure is a risk factor of squamous cell carcinoma (SCC) among fair-skinned populations. However, sun exposure and sun reaction have not been explored in Asians and no gender-specific data were available.
In a case–control study, 176 incident skin cancer cases were recruited from National Cheng-Kung University Medical Center from 1996 to 1999. Controls included 216 age-, gender-, and residency-matched subjects from the southwestern Taiwan. A questionnaire was administered to collect information on life style and other risk factors. Logistic regression analysis was performed to evaluate the association between sun exposure or sun reaction and the risk of SCC by gender.
Early-age (age 15 to 24) and lifetime sun exposure were significantly associated with increased risk of SCC in a dose–response pattern [odds ratio (OR) = 1.49–3.08, trend p = 0.009 and 0.0007, respectively]. After stratified by gender, the third tertile of early-age sun exposure was significantly associated with the SCC risk among men (OR = 3.08). The second and third tertiles of lifetime sun exposure was significantly associated with SCC risk among women (OR = 3.78 and 4.53, respectively). Skin reaction after 2-h sun exposure during childhood and adolescence was not significantly associated with the risk of SCC.
Lifetime sun exposure was more related to SCC risk in women, while early-age sun exposure was more relevant to men’s SCC risk. This may be attributable to different lifestyle between men and women.
Squamous cell carcinoma (SCC); Early age; Lifetime; Sun exposure
Cancer epidemiology is challenging in developing nations, in the absence of reliable pathology-based cancer registries. Clinical experience suggests that the incidence of gastric cancer is high in Honduras, in contrast to the limited available national statistics at the time of study initiation (IARC GLOBOCAN 2002: males 15.2, females 10.8). We estimate the incidence of gastric cancer for Honduras using an endoscopy registry as a complimentary resource.
We conducted a retrospective analysis of incident noncardia gastric adenocarcinoma cases in Western Honduras for the period 2000–2009. This region is well circumscribed geopolitically with a single district hospital and established referral patterns, to provide a unique epidemiological niche to facilitate estimation of incidence rates. A prospective, comprehensive database of all endoscopy procedures from this hospital was utilized at the primary data source. The catchment area for gastroenterology services for the at-risk population was validated by calculating the overall endoscopy utilization rates for each municipality in western Honduras. Incident cases of gastric adenocarcinoma were determined by the endoscopic diagnosis. Pathology services are not financed by the Ministry of Health, and histology data was incorporated when available. Population statistics were obtained from the Honduras National Statistics Institute (INE). Age standardized incidence rates (ASIRs) were calculated using world standard population fractions.
The catchment area for Western Honduras was validated with the municipality threshold of 30 endoscopies per 106 person-years, with inclusion of a total of 40 municipalities. In the Western Honduras catchment area, there were 670 incident cases (439 M, 231 F) of noncardia gastric adenocarcinoma during the study decade 2000–2009. Notably, 67 (10.0%) and 165 (24.6%) of cases were under the ages of 45 and 55, respectively. The case-finding rate was 5.1 endoscopies performed for each new diagnosis of gastric cancer. The ASIRs for the decade were 30.8 for males and 13.9 for females. Clinically, 60.3% of gastric cancers were Borrmann type 3 (ulcerated mass), and evidence of advanced disease with pyloric obstruction was common (35.2%). Subtypes by the Lauren classification were distributed among diffuse (56%), intestinal (34%) and indeterminate (9.9%), in subjects with available pathology (526/670).
The endoscopy procedure registry may serve as a complimentary data resource for gastric cancer incidence estimation in resource-limited nation settings wherein pathology services and cancer registries are absent. The results remain an underestimation in this setting due to the challenges of access-to-care and related factors. The methodology helps to more fully characterize the high incidence of gastric cancer in western Honduras and this region of Central America, and demonstrate the need for additional epidemiology research and interventions focused on prevention and treatment.
Gastric Cancer; Honduras; Cancer Epidemiology; Endoscopy; Incidence Rate; Central America
Chronic inflammation has been proposed as a risk factor for ovarian cancer. Some data suggest that anti-inflammatory medications may be protective against ovarian cancer; however, results have been inconsistent.
We evaluated the risk of epithelial ovarian cancer with regular use of NSAIDs prospectively in the NIH-AARP Diet and Health Study, using Cox proportional hazard models. We also examined the risk of common subtypes of epithelial ovarian cancer (serous, mucinous, endometrioid, clear cell and other epithelial) with regular use of NSAIDs. In addition, we performed meta-analyses summarizing the risk of ovarian cancer with “regular use” of NSAIDs in previously published studies.
We did not observe a significant association between regular use of NSAIDs with ovarian cancer risk in the AARP cohort (aspirin: RR 1.06, 95% CI 0.87–1.29; non-aspirin NSAIDs: RR 0.93, 95% CI 0.74–1.15); however summary estimates from prospective cohort studies demonstrated that use of non-aspirin NSAIDs may reduce the risk of ovarian cancer (RR 0.88, 95% CI 0.77–1.01). Although not significant, we found that mucinous tumors were inversely associated with non-aspirin NSAID use (RR 0.69, 95% CI 0.23–2.10) in the AARP cohort, which was supported by the meta-analysis (RR 0.69, CI 0.50–0.94.)
Although results from the NIH-AARP cohort study were not statistically significant, our meta-analysis suggests that non-aspirin NSAIDs may be protective against ovarian cancer. Additional analyses, focusing on dose, duration, and frequency of NSAID use and accounting for ovarian cancer heterogeneity are necessary to further elucidate the association between NSAID use and ovarian cancer risk.
Aspirin; Non-steroidal anti-inflammatory drugs; Inflammation; Ovarian cancer; Prospective study
Oral and pharyngeal cancer patients diagnosed at an advanced stage experience increased morbidity and mortality relative to those with localized disease. The aim of this study was to assess the impact of dental insurance status and regularity of dental visits on early detection of oral and pharyngeal cancer.
We examined the relationship of dental insurance and frequency of dental visits with stage at diagnosis among 441 oral and pharyngeal cancer cases from a population-based study of head and neck cancer. Ordinal logistic regression models were used to assess the association with stage, and tumor (T) and nodal (N) classification.
Never or rarely going to the dentist was associated with being diagnosed at higher stage for oral and pharyngeal cancer (cumulative OR = 2.28, 95% CI: 1.02–5.10) and oral cancer (cumulative OR = 9.17, 95% CI: 2.70–31.15) compared to those going to the dentist at least annually. Oral and pharyngeal cancer patients who went to the dentist infrequently (cumulative OR = 1.82, 95% CI: 1.09–3.05) or rarely/never (cumulative OR = 3.24, 95% CI: 1.59–6.57) were diagnosed with a higher T classification compared with those who went at least annually.
Receipt of regular dental examinations at least annually may reduce the public health burden of oral and pharyngeal cancer by facilitating earlier detection of the disease.
Dental coverage; oral examination; oral cancer screening; head and neck cancer; early detection
We conducted a case-parent triad study evaluating the role of maternal and offspring genotypes in the folate metabolic pathway on childhood acute lymphoblastic leukemia (ALL) risk.
Childhood ALL case-parent triads (N = 120) were recruited from Texas Children’s Hospital. DNA samples were genotyped using the Sequenom iPLEX MassARRAY for 68 tagSNPs in six folate metabolic pathway genes (MTHFR, MTRR, MTR, DHFR, BHMT, and TYMS). Log-linear modeling was used to examine the associations between maternal and offspring genotypes and ALL.
After controlling for the false discovery rate (<0.1), there were 20 significant maternal effects in the following genes: BHMT (N = 3), MTR (N = 12), and TYMS (N = 5). For instance, maternal genotypes for BHMT rs558133 (relative risk [RR] = 0.51, 95% confidence interval [CI]: 0.30–0.87, P = 0.008, Q = 0.08) and MTR rs2282369 (RR = 0.46, 95% CI: 0.27–0.80, P = 0.004, Q = 0.08) were associated with ALL. There were no significant offspring effects after controlling for the false discovery rate.
This is one of the few studies conducted to evaluate maternal genetic effects in the context of childhood ALL risk. Furthermore, we employed a family-based design that is less susceptible to population stratification bias in the estimation of maternal genetic effects. Our findings suggest that maternal genetic variation in the folate metabolic pathway is relevant in the etiology of childhood ALL. The observed maternal genetic effects support the need for continued research of how the uterine environment may influence risk of ALL.
Acute lymphoblastic leukemia; case-parent triad; folate; genetic epidemiology; pediatric cancer
Previous studies have examined the association between ABO blood group and ovarian cancer risk, with inconclusive results.
In 8 studies participating in the Ovarian Cancer Association Consortium (OCAC), we determined ABO blood groups and diplotypes by genotyping 3 SNPs in the ABO locus. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in each study using logistic regression; individual study results were combined using random effects meta-analysis.
Compared to blood group O, the A blood group was associated with a modestly increased ovarian cancer risk: (OR: 1.09; 95% CI: 1.01–1.18; p=0.03). In diplotype analysis, the AO, but not the AA diplotype was associated with increased risk (AO: OR: 1.11; 95% CI: 1.01–1.22; p=0.03; AA: OR: 1.03; 95% CI: 0.87–1.21; p=0.76). Neither AB nor the B blood groups were associated with risk. Results were similar across ovarian cancer histologic subtypes.
Consistent with most previous reports, the A blood type was associated modestly with increased ovarian cancer risk in this large analysis of multiple studies of ovarian cancer. Future studies investigating potential biologic mechanisms are warranted.
ovarian cancer; ABO blood group; Ovarian Cancer Association Consortium (OCAC); genetic epidemiology