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2.  Toenail Nicotine Level as a Novel Biomarker for Lung Cancer Risk 
American Journal of Epidemiology  2011;173(7):822-828.
The objective of this US study was to assess the association of toenail nicotine level as a novel biomarker with lung cancer risk independent of reported smoking history. A nested case-control study of 210 male lung cancer cases and 630 matched controls aged 40–75 years participating in the Health Professionals Follow-up Study was conducted. Toenail samples collected in 1987 were analyzed for nicotine levels, and incident lung cancer cases were diagnosed between 1988 and 2000. Mean toenail nicotine level among cases was 0.95 ng/mg compared with 0.25 ng/mg among controls (P < 0.0001). In univariate analyses, the relative risk of lung cancer for the highest versus lowest quintiles of toenail nicotine level was 10.50 (95% confidence interval: 5.61, 19.64; P for trend < 0.0001). When the authors adjusted for pack-years from reported smoking history in multivariate analyses, the relative risk for toenail nicotine levels in the highest quintile was still significant in predicting lung cancer risk: 3.57 (95% confidence interval: 1.73, 7.37; P for trend < 0.0001). In conclusion, the toenail nicotine biomarker was found to be a strong predictor of lung cancer independent of smoking history, suggesting that the adverse effects of cigarette smoke may be underestimated in studies based on smoking history only.
PMCID: PMC3105283  PMID: 21367874
cohort studies; lung neoplasms; nails; nicotine; tobacco
3.  Hormone use and lung cancer incidence: the Rancho Bernardo cohort study 
Menopause (New York, N.Y.)  2009;16(5):1044-1048.
This study examines the association of hormone use and lung cancer among women.
This is a prospective study of 2,861 women aged 31 to 79 years from the Rancho Bernardo cohort. After enrollment in 1972 to 1974, women were followed up for 31 years for morbidity and mortality. Incident lung cancer was based on self-report or death certificates. Diagnosis was validated from the California Cancer Registry for cases that occurred after 1988. Cox proportional hazard models were used to estimate the adjusted association of hormone use and lung cancer.
During the 31-year follow-up, 87 women developed lung cancer. There was no association between hormone use and lung cancer (hazard ratio, 1.13; 95% CI, 0.73-1.73). Stratification by age 55 years (proxy for menopause status) showed divergent results. In women 55 years older, lung cancer risk was 1.58 (95% CI, 0.95-2.53), whereas in women younger than 55 years, lung cancer risk was 0.44 (95% CI, 0.16-1.23). The confidence intervals for both groups contained the null value.
Although not statistically significant, our results from a long follow-up suggest that postmenopausal women on hormone therapy may have an increased risk of lung cancer, whereas younger women do not.
PMCID: PMC2743860  PMID: 19387414
Hormones; Lung Cancer; Menopause
4.  The California Tobacco Control Program's effect on adult smokers: (3) Similar effects for African Americans across states 
Tobacco Control  2007;16(2):96-100.
To compare trends in African‐American (AA) and non‐Hispanic white (NHW) smoking between states categorised as having three different levels of tobacco control practice in the 1990s.
Setting and participants
Analysis of 1992–3 to 2001–2 Tobacco Use Supplements to the Current Population Survey for differences in adult (20–64 years) daily smoking prevalence for AAs and NHWs across states: California (CA; high cigarette price/comprehensive programme), New York (NY) and New Jersey (NJ; high cigarette price/no comprehensive programme), and tobacco growing states (TGS; low cigarette price/no comprehensive programme).
From 1992–3 to 2001–2, there were large declines in AA smoking across states (2.7–3.8% decrease/year, adjusted for age, income, education, gender; p<0.05). Adjusted NHW smoking prevalence declined significantly only in CA. AA prevalence declined significantly and did not differ across state groups. In all years, in all state groups, adjusted prevalence was either not significantly different or was lower for AAs than for NHWs. More recent cohorts of AAs appeared to have taken up smoking at lower rates than older cohorts.
There were uniformly large declines in AA smoking from 1992–3 to 2001–2 across states, independent of type of tobacco control strategy. Further research is needed into factors associated with smoking declines among AAs.
PMCID: PMC2598480  PMID: 17400946
5.  The California Tobacco Control Program's effect on adult smokers: (1) Smoking cessation 
Tobacco Control  2007;16(2):85-90.
To estimate national population trends in long‐term smoking cessation by age group and to compare cessation rates in California (CA) with those of two comparison groups of states.
Retrospective smoking history of a population sample from the US: from CA, with a comprehensive tobacco‐control programme since 1989 with the goal of denormalising tobacco use; from New York and New Jersey (NY & NJ), with similar high cigarette prices but no comprehensive programme; and from the tobacco‐growing states (TGS), with low cigarette prices, no tobacco‐control programme and social norms relatively supportive of tobacco use.
Respondents to the Current Population Survey–Tobacco Use Supplements (1992–2002; n = 57 918 non‐Hispanic white ever‐smokers).
Main outcome measures
The proportion of recent ever‐smokers attaining long‐term abstinence (quit ⩾1 year) and the successful‐quit ratio (the proportion of all ever‐smokers abstinent ⩾1 year).
Nationally, long‐term cessation rates increased by 25% from the 1980s to the 1990s, averaging 3.4% per year in the 1990s. Cessation increased for all age groups, and by >40% (p<0.001) among smokers aged 20–34 years. For smokers aged <50 years, higher cigarette prices were associated with higher quitting rates. For smokers aged <35 years, quitting rates in CA were higher than in either comparison group (p<0.05). Half of the ever‐smokers had quit smoking by age 44 years in CA, 47 years in NY & NJ, and by age 54 years in TGS.
Successful smoking cessation increased by 25% during the1990s in the US. Comprehensive tobacco‐control programmes were associated with greater cessation success than were with high cigarette prices alone, although both effects were limited to younger adults.
PMCID: PMC2598468  PMID: 17400944
6.  Reliability of Plasma Carotenoid Biomarkers and Its Relation to Study Power 
Epidemiology (Cambridge, Mass.)  2008;19(2):338-344.
The reliability of biomarkers profoundly impacts validity of their use in epidemiology and can have serious implications for study power and the ability to find true associations. We assessed reliability of plasma carotenoid levels over time and how it could influence study power through sample size and effect-size.
Plasma carotenoid levels were measured in a cohort study of 1323 women participating in the control arm of the Women's Healthy Eating and Living Study. We compared mean plasma levels at baseline, year 1, and year 4 of the study for alpha-carotene, beta-carotene, lycopene, lutein, and beta-cryptoxanthin. Reliability of these levels over time was assessed by Spearman correlations and intraclass correlation.
We found limited variation in mean levels between any 2 time points. Variation did not exceed 8% for lycopene, lutein, and beta-cryptoxanthin, 15% for alpha-carotene, and 18% for beta-carotene. Spearman correlations for individual carotenoids over time varied between 0.50 and 0.80, with lycopene having the lowest correlation. Intraclass correlations ranged from 0.47 to 0.66 for carotenoids.
Intraclass correlations for plasma carotenoids over a period of several years are acceptable for epidemiologic studies. However, such variation is enough to decrease statistical power and increase the sample size needed to detect a given effect.
PMCID: PMC2574518  PMID: 18300693
7.  Differences in Health Symptoms among Residents Living Near Illegal Dump Sites in Los Laureles Canyon, Tijuana, Mexico: A Cross Sectional Survey 
Living near landfills is a known health hazard prompting recognition of environmental injustice. The study aim was to compare self-reported symptoms of ill health among residents of four neighborhoods, living in haphazardly constructed settlements surrounded by illegal dumpsites in Tijuana, Mexico. One adult from each of 388 households located in Los Laureles Canyon were interviewed about demographics, health status, and symptoms. Distance from each residence to both the nearest dumpsite and the canyon bottom was assessed. The neighborhoods were selected from locations within the canyon, and varied with respect to proximity to dump sites. Residents of San Bernardo reported significantly higher frequencies of ill-health symptoms than the other neighborhoods, including extreme fatigue (OR 3.01 (95% CI 1.6–5.5)), skin problems/irritations (OR 2.73 (95% CI 1.3–5.9)), stomach discomfort (OR 2.47 (1.3–4.8)), eye irritation/tears (OR 2.02 (1.2–3.6)), and confusion/difficulty concentrating (OR 2.39 (1.2–4.8)). Proximity to dumpsites did not explain these results, that varied only slightly when adjusted for distance to nearest dumpsite or distance to the canyon bottom. Because San Bernardo has no paved roads, we hypothesize that dust and the toxicants it carries is a possible explanation for this difference. Studies are needed to further document this association and sources of toxicants.
PMCID: PMC4199034  PMID: 25226411
cross-sectional survey; environmental; exposure; hazardous waste; Mexico; Superfund; symptoms
9.  Dietary Intake, Supplement Use, and Survival Among Women Diagnosed with Early Stage Breast Cancer 
Nutrition and cancer  2011;63(3):327-333.
Previous studies examining the relationship between micronutrient intakes and survival following diagnosis of breast cancer have reported mixed results. This may be partly due to considerable variance in amounts of micronutrients consumed from diet and supplements across studies.
Early stage breast cancer survivors (n=3081) completed four 24-hour dietary and supplement recalls at the baseline assessment (1995 to 2000) and were followed for a median of 9.0 years. Mean micronutrient intakes were compared to dietary reference intakes (DRI) to assess micronutrient adequacy for both users and non-users of supplements. Cox regressions were performed to assess whether intakes of selected micronutrients were associated with all-cause mortality.
412 deaths occurred between baseline and August 2009. Among these women, more supplement users had adequate micronutrient intakes than non-users for 15 out of 17 micronutrients. Less than 10% of supplement users (< 2% of non-supplement users) reported levels that exceeded the tolerable upper limit for each micronutrient except magnesium. After adjusting for age, tumor characteristics, and health status variables, micronutrient intakes were not significantly associated with all-cause mortality.
Dietary supplements may improve overall micronutrient intakes of breast cancer survivors. However, vitamin and mineral intakes were not associated with all-cause mortality.
PMCID: PMC3078826  PMID: 21391124
dietary intake; supplement use; breast cancer survival
10.  Tribal casinos in California: the last vestige of indoor smoking 
BMC Public Health  2012;12:144.
High levels of airborne particles from secondhand smoke have been reported in California Indian casinos. Yet, little is known regarding the smoking status of casino patrons, their avoidance of secondhand smoke while visiting, and their views on a hypothetical smoking ban.
Predictors of visiting an Indian casino were assessed among participants of the 2008 California Tobacco Survey (n = 10, 397). Exposure to and avoidance of secondhand smoke were subsequently analyzed among a subset of participants who had visited a casino in the year prior to the survey (n = 3, 361).
Ethnic minorities, older individuals, current smokers and residents of sparsely populated regions of California were more likely than other demographic groups to visit a tribal casino. Avoidance of secondhand smoke was more frequent among the never smokers than former and current smokers, particularly those who last visited a casino lacking physical separation between non-smoking and smoking sections. The never smokers versus current smokers disproportionately expressed a willingness to extend their stay and visit again if smoking were prohibited.
If casinos became smoke free, then it is anticipated that they would be visited by a significantly larger number of Californians, including both patrons and those who otherwise would not have visited a casino.
PMCID: PMC3306736  PMID: 22364487
Secondhand smoke; California tribal casinos; Smoking ban; Smoking prevalence
11.  Desert Dust Exposure Is Associated with Increased Risk of Asthma Hospitalization in Children 
Rationale: Desert dust particles, including quartz, which causes inflammatory responses in the airway in animal studies, are transported to widespread regions around the globe. Epidemiologically, areas impacted by desert dust storms, such as communities in the Middle East and the Caribbean, seem to have higher incidences of asthma than might be expected.
Objectives: We investigated the magnitude of association between airborne mineral dust concentration and hospitalization of children for asthma exacerbation by using Light Detection And Ranging (LIDAR) with a polarization analyzer for an exposure measurement, which can distinguish mineral dust particles from other particles.
Methods: A case-crossover design was used. The exposure measurement was LIDAR's nonspherical extinction coefficient. The outcome measurement was hospitalization of children aged 1 to 15 years for asthma exacerbation in eight principal hospitals in Toyama, a local area in Japan bordering the Japan Sea, during February to April, 2005 to 2009.
Measurements and Main Results: During the study period, there were 620 admissions for asthma exacerbation, and 6 days with a heavy dust event (daily mineral dust concentration > 0.1 mg/m3). Conditional logistic regression showed a statistically significant association between asthma hospitalization and a heavy dust event. The crude odds ratio (OR) of the heavy dust event for hospitalization on the day was 1.88 (95% confidence interval [CI], 1.04–3.41; P = 0.037), and the OR of heavy dust event during the previous week was 1.83 (95% CI, 1.31–2.56; P = 0.00043). The OR adjusted by other air pollutant levels, pollen, and meteorological factors was 1.71 (95% CI, 1.18–2.48; P = 0.0050).
Conclusions: Heavy dust events are associated with an increased risk of hospitalizations for asthma.
PMCID: PMC3159090  PMID: 20656941
Asian dust; Kosa; mineral dust; African dust; quartz
12.  Low To Moderate Alcohol Intake Is Not Associated with Increased Mortality after Breast Cancer 
Both alcohol consumption and obesity have been linked with breast cancer morbidity and mortality. An inverse association between alcohol intake and obesity suggests possible confounding between these variables (and perhaps other factors) with breast cancer outcomes.
Alcohol intake (beer, wine, spirits, and total) was examined in 3088 women previously diagnosed and treated for breast cancer, within an intervention trial that targeted vegetables, fiber, and fat but not alcohol or weight loss. Factors associated with baseline alcohol intake were included in Cox proportional hazards models for recurrence and mortality.
Alcohol intake was significantly associated with higher education and physical activity levels. Neither light alcohol intake nor obesity was significantly associated with breast cancer recurrence, but moderate alcohol intake > 300 g/month was protective against all-cause mortality (HR = 0.69, CI=0.49-0.97) in a proportional hazards model adjusted for obesity. Obese women were 61% more likely to be nondrinkers than drinkers, and 76% more likely to be light drinkers than moderate/heavy drinkers. In non-obese women, alcohol intake > 10 g/month was associated with lower risk of all-cause mortality (HR = 0.68, 95% CI = 0.51-0.91).
Light alcohol intake, regardless of body weight, did not increase the risk of breast cancer recurrence or all-cause mortality in this cohort of middle-aged women previously diagnosed with breast cancer. Alcohol intake was associated with other favorable prognostic indicators that may explain its apparent protective effect in non-obese women.
PMCID: PMC2836421  PMID: 20160253
alcohol; breast cancer; obesity; mortality; recurrence
13.  Greater severity of new onset asthma in allergic subjects who smoke: a 10-year longitudinal study 
Respiratory Research  2011;12(1):16.
Little is known about the association between cigarette smoking and asthma severity. We assessed smoking as a determinant of disease severity and control in a cohort of clinic-referred allergic subjects who developed new onset asthma.
Allergic rhinitis subjects with no asthma (n = 371) were followed-up for 10 years and routinely examined for asthma diagnosis. In those who developed asthma (n = 152), clinical severity and levels of asthma control were determined. Among these subjects, 74 (48.7%) were current smokers, 17 (11.2%) former smokers, and 61 (40.1%) never smokers.
When comparing current or past smokers to never smokers they had a higher risk of severe asthma in the univariate analysis, which became non-significant in the multivariate analysis. On the other hand, the categories of pack-years were significantly related to severe asthma in a dose response relationship in both the univariate and multivariate analysis: compared to 0 pack years, those who smoked 1-10 pack-years had an OR(95% CI) of 1.47(0.46-4.68), those who smoked 11-20 pack-years had an OR of 2.85(1.09-7.46) and those who smoked more than 20 pack-years had an OR of 5.59(1.44-21.67) to develop more severe asthma. Smokers with asthma were also more likely to have uncontrolled disease. A significant dose-response relationship was observed for pack-years and uncontrolled asthma. Compared to 0 pack years, those who smoked 1-10 pack-years had an OR of 5.51(1.73-17.54) and those who smoked more than 10 pack-years had an OR of 13.38(4.57-39.19) to have uncontrolled asthma.
The current findings support the hypothesis that cigarette smoking is an important predictor of asthma severity and poor asthma control.
PMCID: PMC3037316  PMID: 21261960
14.  Time-Varying Effects of Prognostic Factors Associated With Disease-Free Survival in Breast Cancer 
American Journal of Epidemiology  2009;169(12):1463-1470.
Early detection and effective treatments have dramatically improved breast cancer survivorship, yet the risk of relapse persists even 15 years after the initial diagnosis. It is important to identify prognostic factors for late breast cancer events. The authors investigated time-varying effects of tumor characteristics on breast-cancer-free survival using data on 3,088 breast cancer survivors from 4 US states who participated in a randomized dietary intervention trial in 1995–2006, with maximum follow-up through 15 years (median, 9 years). A piecewise constant penalized spline approach incorporating time-varying coefficients was adopted, allowing for deviations from the proportional hazards assumption. This method is more flexible than standard approaches, provides direct estimates of hazard ratios across time intervals, and is computationally tractable. Having a stage II or III tumor was associated with a 3-fold higher hazard of breast cancer than having a stage I tumor during the first 2.5 years after diagnosis; this hazard ratio decreased to 2.1 after 7.7 years, but higher tumor stage remained a significant risk factor. Similar diminishing effects were found for poorly differentiated tumors. Interestingly, having a positive estrogen receptor status was protective up to 4 years after diagnosis but detrimental after 7.7 years (hazard ratio = 1.5). These results emphasize the importance of careful statistical modeling allowing for possibly time-dependent effects in long-term survivorship studies.
PMCID: PMC2733768  PMID: 19403844
breast neoplasms; proportional hazards models; survival
15.  Using a cessation-related outcome index to assess California's cessation progress at the population level 
Tobacco Control  2010;19(Suppl_1):i56-i61.
The California Tobacco Control Program (CTCP) has employed strategies to change social norms around smoking in order to decrease the prevalence of smoking and tobacco-related diseases. Research is scarce on CTCP's impact on overall smoking cessation in California.
Tobacco Use Supplement to the Current Population Survey (TUS-CPS) data from 1992–1993 to 2006–2007 was used to create a cessation-related outcome index (CROI), which was a summarised z score of the following determinants: plan to quit, quit attempt and recent quit rate for each of the 50 US states. CROI trends over the period of six separate TUS-CPSs were plotted for California and other comparison states, for 18–34 year olds and for those 35 years or older separately in the context of historical cigarette price z score trend.
California had a consistently high CROI for both age groups. The CROI trend line increased moderately in California for both age groups despite a declining cigarette price z score trend. In contrast, other selected states with a declining cigarette price z score trend had a declining CROI trend for both age groups.
The increase of CROI in California while cigarette price z score trend declined suggests that the implementation of CTCP, even without a significant direct cessation component, has had a profound impact on cessation outcomes.
PMCID: PMC2976490  PMID: 20382652
Cessation; tobacco control; surveillance; addiction; cessation; surveillance and monitoring; young adults
16.  Longitudinal Biological Exposure to Carotenoids is Associated with Breast Cancer-Free Survival in the Women’s Healthy Eating and Living Study 
In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit, and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4 and 6 years and breast cancer-free survival in the Women’s Healthy Eating and Living (WHEL) Study participants (n = 3043), who had been diagnosed with early stage breast cancer. The primary endpoint was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve (AUC) formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer-free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared to the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval 0.54–0.83) after adjustment. The interaction between study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment.
PMCID: PMC2683031  PMID: 19190138
Carotenoids; Diet; Breast Cancer; Survival; Cohort
17.  The California Tobacco Control Program's effect on adult smokers: (2) Daily cigarette consumption levels 
Tobacco Control  2007;16(2):91-95.
To investigate the association of the California Comprehensive Tobacco Control Program with self‐reported population trends of cigarette consumption during 1992–2002.
Setting and Participants
Participants were non‐Hispanic white daily smokers (aged 20–64 years, n = 24 317) from the Tobacco Use Supplements to the Current Population Survey (1992–2002). We compared age‐specific trends in consumption among daily smokers in three groups of states with differing tobacco control initiatives: California (CA; high cigarette price/comprehensive programme), New York and New Jersey (high cigarette price/no comprehensive programme), and tobacco‐growing states (TGS; low cigarette price/no comprehensive programme).
There was a general decline in cigarette consumption across all age groups in each category of states between 1992 and 2002, except the oldest age group in the TGS . The largest annual decline in the average number of cigarettes per day was observed among daily smokers in CA who were aged ⩾35 years (−0.41 cigarettes/day/year (95% CI −0.52 to −0.3)). This rate was significantly higher than the −0.22 cigarettes/day/year (95% CI −0.3 to −0.16; p<0.02) observed in same‐age daily smokers from New York and New Jersey, and significantly higher than the rate in same‐age daily smokers from the TGS (−0.15 cigarettes/day/year (95% CI −0.22 to −0.08; p<0.002)). There were no significant differences across state groups in the decline observed in daily smokers aged 20–34 years. In 2002, only 12% of daily smokers in CA smoked more than a pack per day, which was significantly lower than the 17% in New York and New Jersey, which again was significantly lower than the 25% in the TGS.
The California Tobacco Control Program was associated with significant declines in cigarette consumption among daily smokers aged ⩾35 years of age, which in turn should lead to declines in tobacco‐related health effects. The decline in consumption among young adult smokers was a national trend.
PMCID: PMC2598465  PMID: 17400945
18.  Perceptions of hookah smoking harmfulness: predictors and characteristics among current hookah users 
Tobacco Induced Diseases  2009;5(1):16.
Tobacco cigarette smoking a well-known cause of cancer and other diseases. Hookah smoking is another form of tobacco use that has rapidly spread in the United State and Europe. This study assessed beliefs about the harmfulness of smoking hookah.
We surveyed hookah users in all cafes that provided hookah to its customers in downtown San Diego, California and nearby areas. A total of 235 hookah users participated in this study.
Average age of study participants was 22 years, 57% were males, and 72% were not cigarette smokers. Whites were more likely to use hookah than the other ethnic groups (33%), older hookah users (26-35 years) were mostly males, and mint flavor of hookah tobacco was the most popular among a wide variety of flavors (23%). There was no significant difference in gender in relation to the wrong perception that hookah is less harmful than cigarettes, but those of Asian ethnicity were much less likely than other ethnic groups to believe that hookah is less harmful than cigarettes. More frequent users of hookah were more likely to believe that hookah is less harmful than cigarettes. The majority of hookah users (58.3%) believe hookah is less harmful than cigarette smoking.
Compared to cigarettes, there appears to be a lack of knowledge about the harmfulness of smoking hookah among users regardless of their demographic background. Education about the harmfulness of smoking hookah and policies to limit its use should be implemented to prevent the spread of this new form of tobacco use.
PMCID: PMC2806861  PMID: 20021672
19.  IGF-1 and IGFBP-1 and Cognitive Function in Older Men and Women 
Both IGF-1 and cognition decrease with age. IGF-1 is positively associated with cognitive function in individuals with dementia and Alzheimer’s disease, but results are inconsistent for healthy individuals.
To assess the association of IGF-1 and IGFBP-1 with three cognitive function tests in a healthy elderly population
Design, Setting, Patients or Other Participants
Men (636) and women (899) from the Rancho Bernardo study (median age 74 years) were assessed in the period between 1988 and 1992 for cognitive function through administering the Mini-Mental State Exam (MMSE), Verbal Fluency (VF), and Trails B tests. Blood samples were obtained at the same time for IGF-1 and IGFBP-1 levels. We assessed the association between biomarkers and cognitive function tests by dichotomizing tests at the clinically-relevant cut-off using logistic regression and by tertiles and continuous IGF-1 and IGFBP-1 levels using multivariate linear regression analyses.
The mean MMSE, VF and Trails B test scores showed better cognitive function with higher IGF-1 tertiles. In multivariate analyses we found verbal fluency and MMSE were each significantly associated with IGF-1 in a dose-response manner for men (P for trend = 0.001), but no cognitive function tests were related to IGF-1 in women. For men, the highest IGFBP-1 tertile was inversely and significantly different from the lowest tertile for the MMSE test only (P for trend =0.02).
IGF-1 was independently and positively related to MMSE and VF in men and IGFBP-1 was inversely associated with MMSE in men. Sex differences in the association needs further investigation.
PMCID: PMC2728156  PMID: 19515112
cognitive function; IGF-1; IGFBP-1
20.  Reproductive Steroid Hormones and Recurrence-Free Survival in Women with a History of Breast Cancer 
Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01−1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03−1.53), and free estradiol (HR, 1.31; 95% CI, 1.03−1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer.
PMCID: PMC2575111  PMID: 18323413
21.  Telephone Counseling Helps Maintain Long-Term Adherence to a High-Vegetable Dietary Pattern12 
The Journal of nutrition  2007;137(10):2291-2296.
Achieving long-term adherence to a dietary pattern is a challenge in many studies investigating the relationship between diet and disease. The Women’s Healthy Eating and Living Study was a multi-institutional randomized trial in 3088 women at risk for breast cancer recurrence. At baseline, the average participant followed a healthy dietary pattern of 7 vegetable and fruit servings, 21 g/d of fiber, and 28.7% energy from fat, although fat intake increased over the enrollment period. Using primarily telephone counseling, the intervention group was encouraged to substantially increase intakes of vegetables, fruits, and fiber while decreasing fat intake. Sets of 24-h dietary recalls were completed on 90% of eligible participants at 1 y and 86% at 4 y. Using a conservative imputation analysis, at 1 y, the intervention group consumed 38% more vegetable servings (100% when including juice) than the comparison group, 20% more fruit, 38% more fiber, 50% more legumes, and 30% more whole grain foods, with a 20% lower intake of energy from fat. At 4 y, the between-group differences were 65% for vegetables (including juice), 25% fruit, 30% fiber, 40% legumes, 30% whole grain foods, and 13% lower intake of energy from fat. The intervention effect on fat intake was similar for early vs. late enrollees. Plasma carotenoid concentrations on a random 28% sample validated self-reported vegetable and fruit intake, with a between-group difference of 66% at 1 y and over 40% at 4 y. This large change will allow testing of hypotheses on the role of dietary change in preventing additional breast cancer events.
PMCID: PMC2064909  PMID: 17885013
22.  Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity 
Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables.
Patients and Methods
A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005.
In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor–positive cancers.
A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.
PMCID: PMC2274898  PMID: 17557947
23.  Influence of a Diet Very High in Vegetables, Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer 
Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival.
To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer.
Design, Setting, and Participants
Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006.
The intervention group (n=1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n=1551) was provided with print materials describing the "5-A-Day" dietary guidelines.
Main Outcome Measures
Invasive breast cancer event (recurrence or new primary) or death from any cause.
From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, −13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80–1.14; P=.63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72–1.15; P=.43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment.
Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period.
Trial Registration Identifier: NCT00003787
PMCID: PMC2083253  PMID: 17635889
24.  Greater risk of incident asthma cases in adults with Allergic Rhinitis and Effect of Allergen Immunotherapy: A Retrospective Cohort Study 
Respiratory Research  2005;6(1):153.
Asthma and rhinitis are often co-morbid conditions. As rhinitis often precedes asthma it is possible that effective treatment of allergic rhinitis may reduce asthma progression.
The aim of our study is to investigate history of allergic rhinitis as a risk factor for asthma and the potential effect of allergen immunotherapy in attenuating the incidence of asthma.
Hospital-referred non-asthmatic adults, aged 18–40 years between 1990 and 1991, were retrospectively followed up until January and April 2000. At the end of follow up, available subjects were clinically examined for asthma diagnosis and history of allergen specific immunotherapy, second-hand smoking and the presence of pets in the household. A total of 436 non-asthmatic adults (332 subjects with allergic rhinitis and 104 with no allergic rhinitis nor history of atopy) were available for final analyses.
The highest OR (odds ratio) associated with a diagnosis of asthma at the end of follow-up was for the diagnosis of allergic rhinitis at baseline (OR, 7.8; 95%CI, 3.1–20.0 in the model containing the covariates of rhinitis diagnosis, sex, second-hand smoke exposure, presence of pets at home, family history of allergic disorders, sensitization to Parietaria judaica; grass pollen; house dust mites; Olea europea: orchard; perennial rye; and cat allergens). Female sex, sensitization to Parietaria judaica and the presence of pets in the home were also significantly predictive of new onset asthma in the same model. Treatment with allergen immunotherapy was significantly and inversely related to the development of new onset asthma (OR, 0.53; 95%CI, 0.32–0.86).
In the present study we found that allergic rhinitis is an important independent risk factor for asthma. Moreover, treatment with allergen immunotherapy lowers the risk of the development of new asthma cases in adults with allergic rhinitis.
PMCID: PMC1351177  PMID: 16381607

Results 1-24 (24)