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Gao J.,National Health Research Institute | Nalls M.A.,U.S. National Institute on Aging | Shi M.,National Health Research Institute | Joubert B.R.,National Health Research Institute | And 5 more authors.
Neurobiology of Aging | Year: 2012

Little is known about gene-environment interactions in Parkinson disease (PD). We examined potential interactions of smoking and caffeine intake with 10 genome-wide association studies single nucleotide polymorphisms (SNPs) at or near the SNCA, MAPT, LRRK2, and HLA loci among 584 PD patients and 1571 controls. The main effects of these SNPs and environmental exposures were consistent with previous reports. Family history of PD was associated with PD risk (odds ratio = 2.71, 95% confidence interval, 1.97-3.74), which was little affected by further adjustment for these SNPs and environmental exposures. Overall, we did not find significant interactions of either smoking or caffeine intake with these SNPs. However, with a combined smoking and caffeine intake exposure, we found a significant interaction with rs2896905 at SLC2A13, near LRRK2 (p uncorrected = 0.0008). Each A allele was associated with a 35% higher PD risk among never smokers with low caffeine intake, but with a 32% lower risk among smokers with high caffeine intake. This study provides preliminary evidence of a potential gene-environment interaction for PD, which should be investigated in future studies. Published by Elsevier Inc. © 2012.


Mahabir S.,Epidemiology and Genetics Research Program | Forman M.R.,University of Texas M. D. Anderson Cancer Center | Dong Y.Q.,University of Texas M. D. Anderson Cancer Center | Park Y.,U.S. National Cancer Institute | And 2 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2010

Background: Using data from a case-control study, we previously reported that low dietary intakes of magnesium (Mg), iron (Fe), zinc (Zn), copper (Cu), but not selenium (Se) and calcium (Ca), were associated with increased lung cancer risk. Due to dietary recall bias in case-control studies, our objective was to assess whether these findings hold in a prospective cohort study. Methods: We analyzed data from the NIH-American Association of Retired Persons Diet and Health study of 482,875 subjects (288,257 men and 194,618 women) who were cancer-free and completed a food frequency questionnaire at enrollment between 1995 and 2003. Cox proportional hazards models were computed to estimate the relative risk adjusted for potential confounders. Results: During a mean follow-up of 7 years, 7,052 lung cancer cases were identified. For all subjects, we observed no significant associations between total (diet + supplement) Ca, Mg, Fe, Cu, Se, and Zn intakes and lung cancer risk. Total Ca intake was protective (P trend < 0.05) for current smokers and subjects with adenocarcinomas. Total Mg intake increased risk (P trend < 0.05) in men and current smokers. Total Fe intake was inversely associated with risk in women (P trend < 0.01). For dietary minerals, Mg increased risk (P trend < 0.05) in all subjects, among men and current smokers. Increased dietary Ca intake reduced risk in women (P trend = 0.05). Dietary Fe decreased risk in all subjects and among women (P trend < 0.05). Mineral intake from supplements did not affect lung cancer risk. Conclusions: Dietary minerals are risk factors for lung cancer. Impact: Dietary mineral consumption may influence lung cancer risk, but the associations differ by type of mineral and population subgroups. ©2010 AACR.


Major J.M.,U.S. National Institutes of Health | Doubeni C.A.,University of Massachusetts Medical School | Freedman N.D.,U.S. National Institutes of Health | Park Y.,U.S. National Institutes of Health | And 5 more authors.
PLoS ONE | Year: 2010

Purpose: Residing in deprived areas may increase risk of mortality beyond that explained by a person's own SES-related factors and lifestyle. The aim of this study was to examine the relation between neighborhood socioeconomic deprivation and all-cause, cancer- and cardiovascular disease (CVD)-specific mortality for men and women after accounting for education and other important person-level risk factors. Methods: In the longitudinal NIH-AARP Study, we analyzed data from healthy participants, ages 50-71 years at study baseline (1995-1996). Deaths (n = 33831) were identified through December 2005. Information on census tracts was obtained from the 2000 US Census. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for quintiles of neighborhood deprivation. Results: Participants in the highest quintile of deprivation had elevated risks for overall mortality (HRmen = 1.17, 95% CI: 1.10, 1.24; HRwomen = 1.13, 95% CI: 1.05, 1.22) and marginally increased risk for cancer deaths (HRmen = 1.09, 95% CI: 1.00, 1.20; HRwomen = 1.09, 95% CI: 0.99, 1.22). CVD mortality associations appeared stronger in men (HR = 1.33, 95% CI: 1.19, 1.49) than women (HR = 1.18, 95% CI: 1.01, 1.38). There was no evidence of an effect modification by education. Conclusion: Higher neighborhood deprivation was associated with modest increases in all-cause, cancer- and CVD-mortality after accounting for many established risk factors.


Song Y.,Harvard University | Xu Q.,Chinese Institute of Basic Medical Sciences | Xu Q.,National Health Research Institute | Park Y.,U.S. National Cancer Institute | And 3 more authors.
Diabetes Care | Year: 2011

OBJECTIVE - Understanding the relationship between multivitamin use and diabetes risk is important given the wide use of multivitamin supplements among U.S. adults. RESEARCH DESIGN AND METHODS - We prospectively examined supplemental use of multivitamins and individual vitamins and minerals assessed in 1995-1996 in relation to self-reported diabetes diagnosed after 2000 among 232,007 participants in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Multivitamin use was assessed by a food-frequency questionnaire at baseline. Odds ratios (ORs) and 95% CIs were calculated by logistic regression models, adjusted for potential confounders. In total, 14,130 cases of diabetes diagnosed after 2000 were included in the analysis. RESULTS - Frequent use of any multivitamins was not associated with risk of diabetes after adjustment for potential confounders and uses of individual supplements. Compared with nonusers of any multivitamins, the multivariate ORs among users were 1.07 (95% CI 0.94-1.21) for taking vitamins less than once per week, 0.97 (0.88-1.06) for one to three times per week, 0.92 (0.84-1.00) for four to six times per week, and 1.02 (0.98-1.06) for seven or more times per week (P for trend = 0.64). Significantly lower risk of diabetes was associated with the use of vitamin C or calcium supplements. The multivariate ORs comparing daily users with nonusers were 0.91 (0.86-0.97) for vitamin C supplements and 0.85 (0.80-0.90) for calcium supplements. Use of vitamin E or other individual vitamin and mineral supplements were not associated with diabetes risk. CONCLUSIONS - In this large cohort of U.S. older adults, multivitamin use was not associated with diabetes risk. The findings of lower diabetes risk among frequent users of vitamin C or calcium supplements warrant further evaluations. © 2011 by the American Diabetes Association.


Trabert B.,U.S. National Institutes of Health | Wentzensen N.,U.S. National Institutes of Health | Yang H.P.,U.S. National Institutes of Health | Sherman M.E.,U.S. National Institutes of Health | And 3 more authors.
International Journal of Cancer | Year: 2013

Given the strong link between use of unopposed estrogens and development of endometrial cancers, estrogens are usually prescribed with a progestin, particularly for women with intact uteri. Some studies suggest that sequential use of progestins may increase risk; however, the moderating effects of usage patterns or patient characteristics, including body mass index (BMI), are unknown. We evaluated menopausal hormone use and incident endometrial cancer (n = 885) in 68,419 postmenopausal women with intact uteri enrolled in the National Institutes of Health-American Association of Retired Persons Diet and Health study. Participants completed a risk factor questionnaire in 1996-1997 and were followed up through 2006. Hazard rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Among 19,131 women reporting exclusive estrogen plus progestin use, 176 developed endometrial cancer (RR = 0.88; 95% CI = 0.74-1.06). Long-duration (≥10 years) sequential (<15 days progestin per month) estrogen plus progestin use was positively associated with risk (RR = 1.88; 95% CI = 1.36-2.60], whereas continuous (>25 days progestin per month) estrogen plus progestin use was associated with a decreased risk (RR = 0.64; 95% CI = 0.49-0.83). Increased risk for sequential estrogen plus progestin was seen only among thin-to-normal weight women (BMI < 25 kg/m 2; RR = 2.53). Our findings support that specific categories of estrogen plus progestin use increases endometrial cancer risk, specifically long durations of sequential progestins, whereas decreased endometrial cancer risk was observed for users of short-duration continuous progestins. Risks were highest among thin-to-normal weight women, presumably reflecting their lower endogenous estrogen levels, suggesting that menopausal hormones and obesity increase endometrial cancer through common etiologic pathways. Copyright © 2012 UICC.

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