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Grant Details

Grant Number: 7R01CA144034-03 Interpret this number
Primary Investigator: Yuan, Jian-Min
Organization: University Of Pittsburgh At Pittsburgh
Project Title: Prospective Studies of Cancer Etiology and Prevention in Shanghai and Singapore
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): 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.

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Publications

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.
Authors: Wu C, Wang Z, Song X, Feng XS, Abnet CC, He J, Hu N, Zuo XB, Tan W, Zhan Q, Hu Z, He Z, Jia W, Zhou Y, Yu K, Shu XO, Yuan JM, Zheng W, Zhao XK, Gao SG, Yuan ZQ, Zhou FY, Fan ZM, Cui JL, Lin HL, Han XN, Li B, Chen X, Dawsey SM, Liao L, Lee MP, Ding T, Qiao YL, Liu Z, Liu Y, Yu D, Chang J, Wei L, Gao YT, Koh WP, Xiang YB, Tang ZZ, Fan JH, Han JJ, Zhou SL, Zhang P, Zhang DY, Yuan Y, Huang Y, Liu C, Zhai K, Qiao Y, Jin G, Guo C, Fu J, Miao X, Lu C, Yang H, Wang C, Wheeler WA, Gail M, Yeager M, Yuenger J, Guo ET, Li AL, Zhang W, Li XM, Sun LD, Ma BG, Li Y, Tang S, Peng XQ, Liu J, Hutchinson A, Jacobs K, Giffen C, Burdette L, Fraumeni JF Jr, Shen H, Ke Y, Zeng Y, Wu T, Kraft P, Chung CC, Tucker MA, Hou ZC, Liu YL, Hu YL, Liu Y, Wang L, Yuan G, Chen LS, Liu X, Ma T, Meng H, Sun L, Li XM, Li XM, Ku JW, Zhou YF, Yang LQ, Wang Z, Li Y, Qige Q, Yang WJ, Lei GY, Chen LQ, Li EM, Yuan L, Yue WB, Wang R, Wang LW, Fan XP, Zhu FH, Zhao WX, Mao YM, Zhang M, Xing GL, Li JL, Han M, Ren JL, Liu B, Ren SW, Kong QP, Li F, Sheyhidin I, Wei W, Zhang YR, Feng CW, Wang J, Yang YH, Hao HZ, Bao QD, Liu BC, Wu AQ, Xie D, Yang WC, Wang L, Zhao XH, Chen SQ, Hong JY, Zhang XJ, Freedman ND, Goldstein AM, Lin D, Taylor PR, Wang LD, Chanock SJ
Source: Nat Genet, 2014 Sep;46(9), p. 1001-6.
EPub date: 2014 Aug 17.
PMID: 25129146
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Dietary patterns and mortality in a Chinese population.
Authors: Odegaard AO, Koh WP, Yuan JM, Gross MD, Pereira MA
Source: Am J Clin Nutr, 2014 Sep;100(3), p. 877-83.
EPub date: 2014 Jul 23.
PMID: 25057151
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Breast cancer risk assessment using genetic variants and risk factors in a Singapore Chinese population.
Authors: Lee CP, Irwanto A, Salim A, Yuan JM, Liu J, Koh WP, Hartman M
Source: Breast Cancer Res, 2014 Jun 18;16(3), p. R64.
EPub date: 2014 Jun 18.
PMID: 24941967
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Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population.
Authors: SIGMA Type 2 Diabetes Consortium, Estrada K, Aukrust I, Bjørkhaug L, Burtt NP, Mercader JM, García-Ortiz H, Huerta-Chagoya A, Moreno-Macías H, Walford G, Flannick J, Williams AL, Gómez-Vázquez MJ, Fernandez-Lopez JC, Martínez-Hernández A, Centeno-Cruz F, Mendoza-Caamal E, Revilla-Monsalve C, Islas-Andrade S, Córdova EJ, Soberón X, González-Villalpando ME, Henderson E, Wilkens LR, Le Marchand L, Arellano-Campos O, Ordóñez-Sánchez ML, Rodríguez-Torres M, Rodríguez-Guillén R, Riba L, Najmi LA, Jacobs SB, Fennell T, Gabriel S, Fontanillas P, Hanis CL, Lehman DM, Jenkinson CP, Abboud HE, Bell GI, Cortes ML, Boehnke M, González-Villalpando C, Orozco L, Haiman CA, Tusié-Luna T, Aguilar-Salinas CA, Altshuler D, Njølstad PR, Florez JC, MacArthur DG, Jiménez-Morales S
Source: JAMA, 2014 Jun 11;311(22), p. 2305-14.
PMID: 24915262
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Burden of total and cause-specific mortality related to tobacco smoking among adults aged ? 45 years in Asia: a pooled analysis of 21 cohorts.
Authors: Zheng W, McLerran DF, Rolland BA, Fu Z, Boffetta P, He J, Gupta PC, Ramadas K, Tsugane S, Irie F, Tamakoshi A, Gao YT, Koh WP, Shu XO, Ozasa K, Nishino Y, Tsuji I, Tanaka H, Chen CJ, Yuan JM, Ahn YO, Yoo KY, Ahsan H, Pan WH, Qiao YL, Gu D, Pednekar MS, Sauvaget C, Sawada N, Sairenchi T, Yang G, Wang R, Xiang YB, Ohishi W, Kakizaki M, Watanabe T, Oze I, You SL, Sugawara Y, Butler LM, Kim DH, Park SK, Parvez F, Chuang SY, Fan JH, Shen CY, Chen Y, Grant EJ, Lee JE, Sinha R, Matsuo K, Thornquist M, Inoue M, Feng Z, Kang D, Potter JD
Source: PLoS Med, 2014 Apr;11(4), p. e1001631.
EPub date: 2014 Apr 22.
PMID: 24756146
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Coffee, alcohol and other beverages in relation to cirrhosis mortality: the Singapore Chinese Health Study.
Authors: Goh GB, Chow WC, Wang R, Yuan JM, Koh WP
Source: Hepatology, 2014 Aug;60(2), p. 661-9.
EPub date: 2014 Jun 24.
PMID: 24753005
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Sleep duration and risk of stroke mortality among Chinese adults: Singapore Chinese health study.
Authors: Pan A, De Silva DA, Yuan JM, Koh WP
Source: Stroke, 2014 Jun;45(6), p. 1620-5.
EPub date: 2014 Apr 17.
PMID: 24743442
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Dietary soy intake is not associated with risk of cardiovascular disease mortality in Singapore Chinese adults.
Authors: Talaei M, Koh WP, van Dam RM, Yuan JM, Pan A
Source: J Nutr, 2014 Jun;144(6), p. 921-8.
EPub date: 2014 Apr 3.
PMID: 24699802
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Cigarette smoking and risk of total knee replacement for severe osteoarthritis among Chinese in Singapore--the Singapore Chinese health study.
Authors: Leung YY, Ang LW, Thumboo J, Wang R, Yuan JM, Koh WP
Source: Osteoarthritis Cartilage, 2014 Jun;22(6), p. 764-70.
EPub date: 2014 Mar 28.
PMID: 24680935
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Coffee intake and gastric cancer risk: the Singapore Chinese health study.
Authors: Ainslie-Waldman CE, Koh WP, Jin A, Yeoh KG, Zhu F, Wang R, Yuan JM, Butler LM
Source: Cancer Epidemiol Biomarkers Prev, 2014 Apr;23(4), p. 638-47.
EPub date: 2014 Mar 8.
PMID: 24608187
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Adherence to a vegetable-fruit-soy dietary pattern or the Alternative Healthy Eating Index is associated with lower hip fracture risk among Singapore Chinese.
Authors: Dai Z, Butler LM, van Dam RM, Ang LW, Yuan JM, Koh WP
Source: J Nutr, 2014 Apr;144(4), p. 511-8.
EPub date: 2014 Feb 26.
PMID: 24572035
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