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 #
1R01CA144034-01
Application #
7789956
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
2010-01-15
Budget End
2010-12-31
Support Year
1
Fiscal Year
2010
Total Cost
$1,546,796
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Soh, Avril Z; Chee, Cynthia B E; Wang, Yee-Tang et al. (2018) THE AUTHORS REPLY. Am J Epidemiol 187:1572-1573
Talaei, Mohammad; Hosseini, Naeimeh; Koh, Angela S et al. (2018) Association of ""Elevated Blood Pressure"" and ""Stage 1 Hypertension"" With Cardiovascular Mortality Among an Asian Population. J Am Heart Assoc 7:
Chen, Guo-Chong; Koh, Woon-Puay; Yuan, Jian-Min et al. (2018) Green leafy and cruciferous vegetable consumption and risk of type 2 diabetes: results from the Singapore Chinese Health Study and meta-analysis. Br J Nutr 119:1057-1067
Acheampong, Teofilia; Yuan, Jian-Min; Koh, Woon Puay et al. (2018) Occupational exposure to endocrine disrupting substances and the risk of breast Cancer: the Singapore Chinese health study. BMC Public Health 18:929
Premenopausal Breast Cancer Collaborative Group; Schoemaker, Minouk J; Nichols, Hazel B et al. (2018) Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women. JAMA Oncol 4:e181771
Koh, Angela S; Gao, Fei; Liu, Jin et al. (2018) Metabolomic profile of arterial stiffness in aged adults. Diab Vasc Dis Res 15:74-80
Loo, Wai Mun; Goh, George Boon-Bee; Wang, Yeli et al. (2018) Enhanced Liver Fibrosis Score as a Predictor of Hepatocellular Carcinoma. Clin Chem 64:1404-1405
Lu, Yonghai; Wang, Yeli; Zou, Li et al. (2018) Serum Lipids in Association With Type 2 Diabetes Risk and Prevalence in a Chinese Population. J Clin Endocrinol Metab 103:671-680
Yii, Anthony C; Soh, Avril Z; Chee, Cynthia B E et al. (2018) Asthma, Sinonasal Disease, and the Risk of Active Tuberculosis. J Allergy Clin Immunol Pract :
Ji, Xuemei; Bossé, Yohan; Landi, Maria Teresa et al. (2018) Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk. Nat Commun 9:3221

Showing the most recent 10 out of 175 publications