Yikyung Park

Genome-wide association study reveals genetic risk underlying Parkinson's disease

We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinsons disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding α-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 × 10−16) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 × 10−16). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 × 10−8) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 × 10−5). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.

Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults

IMPORTANCEnLeisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood.nnnOBJECTIVEnTo determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking.nnnDESIGN, SETTING, AND PARTICIPANTSnWe pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015.nnnEXPOSURESnLeisure-time physical activity of a moderate to vigorous intensity.nnnMAIN OUTCOMES AND MEASURESnIncident cancer during follow-up.nnnRESULTSnA total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186u202f932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16-1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers.nnnCONCLUSIONS AND RELEVANCEnLeisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.

Dietary fiber intake and risk of breast cancer in postmenopausal women: the National Institutes of Health–AARP Diet and Health Study

BACKGROUNDnAlthough dietary fiber has been hypothesized to lower risk of breast cancer by modulating estrogen metabolism, the association between dietary fiber intake and risk of breast cancer by hormone receptor status is unclear.nnnOBJECTIVEnThe objective was to examine the relation of dietary fiber intake to breast cancer by hormone receptor status and histologic type among postmenopausal women in the National Institutes of Health-AARP Diet and Health Study (n = 185,598; mean age: 62 y).nnnDESIGNnDietary intakes were assessed with a food-frequency questionnaire. Incident breast cancer cases were identified through linkage with state cancer registries. Cox proportional hazard models were used to estimate relative risks (RRs) and 2-sided 95% CIs.nnnRESULTSnDuring an average of 7 y of follow-up, 5461 breast cancer cases were identified, of which 3341 cases had estrogen receptor (ER) and progesterone receptor (PR) status. Dietary fiber intake was inversely associated with breast cancer risk [RR for the highest quintile (Q5) compared with the lowest quintile (Q1): 0.87; 95% CI: 0.77, 0.98; P for trend: 0.02]. The inverse association appeared to be stronger for ER(-)/PR(-) tumors (RR(Q5vsQ1): 0.56; 95% CI: 0.35, 0.90; P for trend: 0.008; 366 cases) than for ER(+)/PR(+) tumors (RR(Q5vsQ1): 0.95; 95% CI: 0.76, 1.20; P for trend: 0.47; 1641 cases). The RR(Q5vsQ1) of lobular tumors was 0.66 (95% CI: 0.44, 0.97; P for trend: 0.04), and the RR(Q5vsQ1) of ductal tumors was 0.90 (95% CI: 0.77, 1.04; P for trend: 0.10). Fiber from grains, fruit, vegetables, and beans was not related to breast cancer.nnnCONCLUSIONnOur findings suggest that dietary fiber can play a role in preventing breast cancer through nonestrogen pathways among postmenopausal women.

Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies

ObjectiveTo evaluate the associations between intakes of vitamins A, C, and E and risk of colon cancer.MethodsUsing the primary data from 13 cohort studies, we estimated study- and sex-specific relative risks (RR) with Cox proportional hazards models and subsequently pooled RRs using a random effects model.ResultsAmong 676,141 men and women, 5,454 colon cancer cases were identified (7–20xa0years of follow-up across studies). Vitamin A, C, and E intakes from food only were not associated with colon cancer risk. For intakes from food and supplements (total), the pooled multivariate RRs (95% CI) were 0.88 (0.76–1.02, >4,000 vs. ≤1,000 μg/day) for vitamin A, 0.81 (0.71–0.92, >600 vs. ≤100xa0mg/day) for vitamin C, and 0.78 (0.66–0.92, >200 vs. ≤6xa0mg/day) for vitamin E. Adjustment for total folate intake attenuated these associations, but the inverse associations with vitamins C and E remained significant. Multivitamin use was significantly inversely associated with colon cancer risk (RRxa0=xa00.88, 95% CI: 0.81–0.96).ConclusionsModest inverse associations with vitamin C and E intakes may be due to high correlations with folate intake, which had a similar inverse association with colon cancer. An inverse association with multivitamin use, a major source of folate and other vitamins, deserves further study.

Ambient Particulate Matter Air Pollution Exposure and Mortality in the NIH-AARP Diet and Health Cohort

Background: Outdoor fine particulate matter (≤ 2.5 μm; PM2.5) has been identified as a global health threat, but the number of large U.S. prospective cohort studies with individual participant data remains limited, especially at lower recent exposures. Objectives: We aimed to test the relationship between long-term exposure PM2.5 and death risk from all nonaccidental causes, cardiovascular (CVD), and respiratory diseases in 517,041 men and women enrolled in the National Institutes of Health-AARP cohort. Methods: Individual participant data were linked with residence PM2.5 exposure estimates across the continental United States for a 2000–2009 follow-up period when matching census tract–level PM2.5 exposure data were available. Participants enrolled ranged from 50 to 71 years of age, residing in six U.S. states and two cities. Cox proportional hazard models yielded hazard ratio (HR) estimates per 10 μg/m3 of PM2.5 exposure. Results: PM2.5 exposure was significantly associated with total mortality (HR = 1.03; 95% CI: 1.00, 1.05) and CVD mortality (HR = 1.10; 95% CI: 1.05, 1.15), but the association with respiratory mortality was not statistically significant (HR = 1.05; 95% CI: 0.98, 1.13). A significant association was found with respiratory mortality only among never smokers (HR = 1.27; 95% CI: 1.03, 1.56). Associations with 10-μg/m3 PM2.5 exposures in yearly participant residential annual mean, or in metropolitan area-wide mean, were consistent with baseline exposure model results. Associations with PM2.5 were similar when adjusted for ozone exposures. Analyses of California residents alone also yielded statistically significant PM2.5 mortality HRs for total and CVD mortality. Conclusions: Long-term exposure to PM2.5 air pollution was associated with an increased risk of total and CVD mortality, providing an independent test of the PM2.5–mortality relationship in a new large U.S. prospective cohort experiencing lower post-2000 PM2.5 exposure levels. Citation: Thurston GD, Ahn J, Cromar KR, Shao Y, Reynolds HR, Jerrett M, Lim CC, Shanley R, Park Y, Hayes RB. 2016. Ambient particulate matter air pollution exposure and mortality in the NIH-AARP Diet and Health cohort. Environ Health Perspect 124:484–490; http://dx.doi.org/10.1289/ehp.1509676

Alcohol Consumption, Folate Intake, Hepatocellular Carcinoma, and Liver Disease Mortality

Background: Excessive alcohol consumption is a well-established risk factor for liver disease and hepatocellular carcinoma (HCC). Previous studies have found that increased alcohol consumption can lead to lower absorption of folate. Conversely, higher folate intake has been inversely associated with liver damage and HCC. In the current study, we investigate the effect of alcohol consumption and folate intake on HCC incidence and liver disease mortality in the NIH–American Association of Retired Persons Diet and Health Study. Methods: The study population included 494,743 participants who reported at baseline their dietary intake for the previous year. Alcohol and folate were analyzed with hazards ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards regression models adjusted for age, sex, race, education, smoking, body mass index, and diabetes. HCC incidence (n = 435) was determined through 2006 via linkage with cancer registries, and liver disease mortality (n = 789) was determined through 2008 via linkage to the U.S. Social Security Administration Death Master File and the National Death Index Plus by the National Center for Health Statistics. Results: Consumption of more than three drinks per day was positively associated with both HCC incidence (HR: 1.92; 95%CI: 1.42–2.60) and liver disease mortality (HR: 5.84; 95%CI: 4.81–7.10), whereas folate intake was associated with neither outcome. Folate, however, modified the relationship between alcohol and HCC incidence (Pinteraction = 0.03), but had no effect on the relationship between alcohol and liver disease mortality (Pinteraction = 0.54). Conclusions: These results suggest that higher folate intake may ameliorate the effect of alcohol consumption on the development of HCC. Impact: Folate intake may be beneficial in the prevention of alcohol-associated HCC. Cancer Epidemiol Biomarkers Prev; 22(3); 415–21. ©2013 AACR.

Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype: Pooled Analysis of 22 Prospective Studies

BACKGROUNDnGreater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality.nnnMETHODSnThis large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information.nnnRESULTSnDuring follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5u2009cm)u2009=u20091.07 [1.04-1.10], BMI (per 5u2009kg/m2)u2009=u20091.06 [1.02-1.10], waist circumference (per 5u2009cm)u2009=u20091.03 [1.01-1.05], young-adult BMI (per 5u2009kg/m2)u2009=u20091.13 [1.02-1.25], and adulthood BMI gain (per 5u2009kg/m2)u2009=u20091.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (pu2009=u20090.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality.nnnCONCLUSIONnThe results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.

Index-based dietary patterns and risk of head and neck cancer in a large prospective study

BACKGROUNDnHead and neck cancer (HNC) is the seventh most common cancer worldwide. Although diet has been proposed to play an important role in HNC, few associations with diet have been convincing other than alcohol intake. Studies of dietary patterns that examine overall diets may provide broader insight than studies of individual foods. Little is known about the association between dietary patterns and risk of HNC.nnnOBJECTIVEnWe prospectively evaluated the association between 2 index-based dietary patterns [ie, the Healthy Eating Index-2005 (HEI-2005) and alternate Mediterranean Diet Score (aMED)] and risk of head and neck squamous cell carcinoma.nnnDESIGNnWe included 494,967 participants from the NIH-AARP Diet and Health study (1995-2006). HRs (95% CIs) were estimated by using Cox regression. Scores for the HEI-2005 and aMED were calculated on the basis of diet assessed by using a baseline food-frequency questionnaire. Higher scores reflected adherence to dietary recommendations for healthy eating. Our main outcome was the incidence of HNC, including cancer of the larynx, oral cavity, and orohypopharynx.nnnRESULTSnA total of 1868 HNC cases were identified during follow-up. Higher HEI-2005 scores were associated with reduced risk of HNC in men [HR: 0.74 (95% CI: 0.61, 0.89) for highest compared with lowest quintiles; P-trend = 0.0008] and women [HR: 0.48; 95% CI: 0.33, 0.70; P-trend < 0.0001]. High aMED scores were also associated with lower HNC risk in men (HR: 0.80; 95% CI: 0.64, 1.01; P-trend = 0.002) and women (HR: 0.42; 95% CI: 0.24, 0.74; P-trend < 0.0001). Associations were similar among subsites. We did not find significant interactions between smoking and alcohol intake and each index on HNC risk.nnnCONCLUSIONSnHEI-2005 and aMED scores were associated inversely with risk of HNC. Large interventional studies are required to assess the causality before conveying definite public health messages.

Intakes of folate, methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study

Background:Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis. Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer.Methods:We prospectively examined the association between self-reported intakes of folate, methionine, vitamin B6, and vitamin B12 and gastric and esophageal cancer in 492u2009293 men and women.Results:We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate (relative risk (95% confidence interval): Q1 vs Q3, 1.91 (1.17, 3.10)), but no association with high intake. Folate intake was not associated with esophageal adenocarcinoma, gastric cardia adenocarcinoma, or non-cardia gastric adenocarcinoma. The intakes of methionine, vitamin B6, and vitamin B12 were not associated with esophageal and gastric cancer.Conclusion:Low intake of folate was associated with increased risk of esophageal squamous cell carcinoma.

Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies.

Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow‐up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study‐specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥45 vs. <5 g/day: advanced 0.83, 0.70–0.99; trend test p value 0.29), fatal, 0.69, 0.59–0.82, trend test p value 0.16). Participants who ate ≥25 versus <5 g/day of eggs (1 egg ∼ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01–1.28, trend test p value 0.01; fatal 1.14, 1.00–1.30, trend test p value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation.