This proposal seeks funding to continue the observational follow-up of the 81,501 middle-aged and older Chinese men and women participants of the Shanghai and Singapore cohort studies for another 5 five years, to accrue and validate a substantially increased number of cancer endpoints in order to evaluate important questions related to lifestyle, biochemical markers, genetic markers, and gene-environment interactions on cancer risk. The Shanghai cohort was assembled in 1986-1989 and the Singapore cohort in 1993-1998. In addition to data collected at baseline and follow-up interviews, blood and urine samples were collected from more than 50,000 subjects at baseline and stored in ultra-low temperature condition since their collection. The vigorous and effective follow-up procedures kept the loss of follow-up to be minimal;to date, only approximately 880 (1%) original cohort participants have been lost to follow-up over the past 20 years. These databases have been serving unique resources for a large number of projects for research on cancer etiology and prevention. In the next 5 five years, we also propose to conduct a series of nested case-control studies within the two cohorts to elucidate the role of environmental exposure, genetic variants and DNA methylation in the development of lung or liver cancer. The primary scientific aims are: (1) to assess the independent role of polycyclic aromatic hydrocarbons (PAH), 1,3-butadiene, acrolein, benzene, and ethylene oxide in the development of lung cancer among smokers;(2) to assess independent role of PAH, 1,3-butadiene, acrolein, benzene, and ethylene oxide in the development of lung cancer among lifelong nonsmokers;(3) to assess the role of methyl groups - S-adenosylmethionine, S-adenosylhomocysteine, methionine, choline, homocysteine, folate, vitamins B6 and B12 in the development of liver cancer;(4) to assess the role of genetic polymorphisms influencing methyl group metabolism in the development of liver cancer, and their modifying effect on the associations between methyl groups and liver cancer risk;and (5) to assess the role of global DNA hypomethylation in the development of liver cancer. The proposed studies with prospective study design, available pre-diagnostic blood and urine samples, and large sample sizes will provide novel and definitive data to accomplish these scientific aims. Furthermore, findings of the proposed studies will provide insights for the understanding of the role of methyl groups, the donor of DNA methylation, in human hepatocarcinogenesis. The ultimate goal of the proposed research is the development of an effective set of non-invasive, predictive markers that allow for the identification of the relatively small fraction of individuals who are at very high risk for lung or liver cancer. People with high risk could take primary preventive measures to reduce their risk, or undergo regular screening for early detection of the malignancies when clinical treatment is more effective.

Public Health Relevance

The Shanghai and Singapore cohort studies are ongoing observational follow-up investigation of environmental and genetic factors on human cancers in 81,501 middle-aged and older Chinese men and women beginning in 1986 and 1993, respectively. The proposed studies within these two cohorts will identify a set of non-invasive, predictive markers of lung and liver cancer development. People with high risk could take primary preventive measures to reduce their risk, or undergo regular screening for early detection of the malignancies when clinical treatment is more effective. The findings of the proposed study will have great impact on reducing incidence and mortality of lung and liver cancers in humans.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA144034-04
Application #
8426009
Study Section
Special Emphasis Panel (ZRG1-PSE-A (03))
Program Officer
Su, Joseph
Project Start
2010-01-15
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
4
Fiscal Year
2013
Total Cost
$1,350,374
Indirect Cost
$191,423
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Huang, Joyce Y; Butler, Lesley M; Midttun, Øivind et al. (2016) Serum B6 vitamers (pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid) and pancreatic cancer risk: two nested case-control studies in Asian populations. Cancer Causes Control 27:1447-1456
Dai, Zhaoli; Wang, Renwei; Ang, Li-Wei et al. (2016) Bone turnover biomarkers and risk of osteoporotic hip fracture in an Asian population. Bone 83:171-7
Yan, Bei; Yang, Li-Ming; Hao, Li-Peng et al. (2016) Determinants of Quality of Life for Breast Cancer Patients in Shanghai, China. PLoS One 11:e0153714
Huang, Joyce Y; Butler, Lesley M; Wang, Renwei et al. (2016) Dietary Intake of One-Carbon Metabolism-Related Nutrients and Pancreatic Cancer Risk: The Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev 25:417-24
Salim, Agus; Tai, E Shyong; Tan, Vincent Y et al. (2016) C-reactive protein and serum creatinine, but not haemoglobin A1c, are independent predictors of coronary heart disease risk in non-diabetic Chinese. Eur J Prev Cardiol 23:1339-49
Pan, An; Teng, Gim Gee; Yuan, Jian-Min et al. (2016) Bidirectional Association between Diabetes and Gout: the Singapore Chinese Health Study. Sci Rep 6:25766
Yuan, Jian-Min; Nelson, Heather H; Butler, Lesley M et al. (2016) Genetic determinants of cytochrome P450 2A6 activity and biomarkers of tobacco smoke exposure in relation to risk of lung cancer development in the Shanghai cohort study. Int J Cancer 138:2161-71
Sun, Ye; Koh, Hiromi W L; Choi, Hyungwon et al. (2016) Plasma fatty acids, oxylipins, and risk of myocardial infarction: the Singapore Chinese Health Study. J Lipid Res 57:1300-7
Koh, Angela S; Talaei, Mohammad; Pan, An et al. (2016) Systolic blood pressure and cardiovascular mortality in middle-aged and elderly adults - The Singapore Chinese Health Study. Int J Cardiol 219:404-9
Quan, Lei; Chattopadhyay, Koushik; Nelson, Heather H et al. (2016) Differential association for N-acetyltransferase 2 genotype and phenotype with bladder cancer risk in Chinese population. Oncotarget 7:40012-40024

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