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Grant Details

Grant Number: 5R01CA144034-04 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: 2013
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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.

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Publications

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
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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Joint effects of known type 2 diabetes susceptibility loci in genome-wide association study of Singapore Chinese: the Singapore Chinese health study.
Authors: Chen Z, Pereira MA, Seielstad M, Koh WP, Tai ES, Teo YY, Liu J, Hsu C, Wang R, Odegaard AO, Thyagarajan B, Koratkar R, Yuan JM, Gross MD, Stram DO
Source: PLoS One, 2014;9(2), p. e87762.
EPub date: 2014 Feb 10.
PMID: 24520337
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Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium.
Authors: Chen Y, Copeland WK, Vedanthan R, Grant E, Lee JE, Gu D, Gupta PC, Ramadas K, Inoue M, Tsugane S, Tamakoshi A, Gao YT, Yuan JM, Shu XO, Ozasa K, Tsuji I, Kakizaki M, Tanaka H, Nishino Y, Chen CJ, Wang R, Yoo KY, Ahn YO, Ahsan H, Pan WH, Chen CS, Pednekar MS, Sauvaget C, Sasazuki S, Yang G, Koh WP, Xiang YB, Ohishi W, Watanabe T, Sugawara Y, Matsuo K, You SL, Park SK, Kim DH, Parvez F, Chuang SY, Ge W, Rolland B, McLerran D, Sinha R, Thornquist M, Kang D, Feng Z, Boffetta P, Zheng W, He J, Potter JD
Source: BMJ, 2013 Oct 1;347, p. f5446.
EPub date: 2013 Oct 1.
PMID: 24473060
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Body mass index and risk of pancreatic cancer in a Chinese population.
Authors: Untawale S, Odegaard AO, Koh WP, Jin AZ, Yuan JM, Anderson KE
Source: PLoS One, 2014;9(1), p. e85149.
EPub date: 2014 Jan 15.
PMID: 24454807
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Urinary tobacco smoke-constituent biomarkers for assessing risk of lung cancer.
Authors: Yuan JM, Butler LM, Stepanov I, Hecht SS
Source: Cancer Res, 2014 Jan 15;74(2), p. 401-11.
EPub date: 2014 Jan 9.
PMID: 24408916
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Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico.
Authors: SIGMA Type 2 Diabetes Consortium, Williams AL, Jacobs SB, Moreno-Macías H, Huerta-Chagoya A, Churchhouse C, Márquez-Luna C, García-Ortíz H, Gómez-Vázquez MJ, Burtt NP, Aguilar-Salinas CA, González-Villalpando C, Florez JC, Orozco L, Haiman CA, Tusié-Luna T, Altshuler D
Source: Nature, 2014 Feb 6;506(7486), p. 97-101.
EPub date: 2013 Dec 25.
PMID: 24390345
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Serum estrogen receptor bioactivity and breast cancer risk among postmenopausal women.
Authors: Lim VW, Li J, Gong Y, Jin A, Yuan JM, Yong EL, Koh WP
Source: Endocr Relat Cancer, 2014 Apr;21(2), p. 263-73.
EPub date: 2014 Feb 27.
PMID: 24322303
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Impact of postdiagnosis smoking on long-term survival of cancer patients: the Shanghai cohort study.
Authors: Tao L, Wang R, Gao YT, Yuan JM
Source: Cancer Epidemiol Biomarkers Prev, 2013 Dec;22(12), p. 2404-11.
PMID: 24319070
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Tobacco-specific N-nitrosamine exposures and cancer risk in the Shanghai Cohort Study: remarkable coherence with rat tumor sites.
Authors: Stepanov I, Sebero E, Wang R, Gao YT, Hecht SS, Yuan JM
Source: Int J Cancer, 2014 May 15;134(10), p. 2278-83.
EPub date: 2013 Nov 18.
PMID: 24243522
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Cancer prevention by green tea: evidence from epidemiologic studies.
Authors: Yuan JM
Source: Am J Clin Nutr, 2013 Dec;98(6 Suppl), p. 1676S-1681S.
EPub date: 2013 Oct 30.
PMID: 24172305
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Urinary metabolites of a polycyclic aromatic hydrocarbon and volatile organic compounds in relation to lung cancer development in lifelong never smokers in the Shanghai Cohort Study.
Authors: Yuan JM, Butler LM, Gao YT, Murphy SE, Carmella SG, Wang R, Nelson HH, Hecht SS
Source: Carcinogenesis, 2014 Feb;35(2), p. 339-45.
EPub date: 2013 Oct 22.
PMID: 24148823
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Plasma S-adenosylmethionine, DNMT polymorphisms, and peripheral blood LINE-1 methylation among healthy Chinese adults in Singapore.
Authors: Inoue-Choi M, Nelson HH, Robien K, Arning E, Bottiglieri T, Koh WP, Yuan JM
Source: BMC Cancer, 2013 Aug 17;13(1), p. 389.
EPub date: 2013 Aug 17.
PMID: 23957506
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Dietary fiber intake modifies the association between secondhand smoke exposure and coronary heart disease mortality among Chinese non-smokers in Singapore.
Authors: Clark ML, Butler LM, Koh WP, Wang R, Yuan JM
Source: Nutrition, 2013 Nov-Dec;29(11-12), p. 1304-9.
EPub date: 2013 Jul 30.
PMID: 23911218
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