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Grant Details

Grant Number: 7R01CA144034-03 Interpret this number
Primary Investigator: Yuan, Jian-Min
Organization: University Of 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

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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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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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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Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma.
Authors: Butler LM, Arning E, Wang R, Bottiglieri T, Govindarajan S, Gao YT, Yuan JM
Source: Cancer Epidemiol Biomarkers Prev, 2013 Oct;22(10), p. 1884-93.
EPub date: 2013 Jul 29.
PMID: 23897582
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Protective effects of dietary carotenoids on risk of hip fracture in men: the Singapore Chinese Health Study.
Authors: Dai Z, Wang R, Ang LW, Low YL, Yuan JM, Koh WP
Source: J Bone Miner Res, 2014 Feb;29(2), p. 408-17.
PMID: 23857780
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Higher parity is associated with an increased risk of type-II diabetes in Chinese women: the Singapore Chinese Health Study.
Authors: Mueller NT, Mueller NJ, Odegaard AO, Gross MD, Koh WP, Yuan JM, Pereira MA
Source: BJOG, 2013 Nov;120(12), p. 1483-9.
EPub date: 2013 Jun 21.
PMID: 23786390
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Mitochondrial DNA copy number is associated with breast cancer risk.
Authors: Thyagarajan B, Wang R, Nelson H, Barcelo H, Koh WP, Yuan JM
Source: PLoS One, 2013;8(6), p. e65968.
EPub date: 2013 Jun 12.
PMID: 23776581
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