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Shanghai Cohort Study

Lead Contact and/or Principal Investigator (PI):

• Jian-Min Yuan, M.D., M.P.H., Ph.D.
  Masonic Cancer Center
  University of Minnesota

Funded Since: 1987
Funding Source: NCI Extramural Program (Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences; CA144034)
Year(s) of Enrollment: 1986-1989

The Shanghai Cohort Study consists of 18,244 men in Shanghai, China, assembled during 1986-1989 when subjects were between the ages of 45 and 64 years. At recruitment, all cohort members provided detailed dietary and medical histories as well as blood and urine specimens. In the follow-up of 2000-2001, buccal cells were collected from 13,815 original cohort participants (92% of all surviving cohort members).

The cohort has been followed for the occurrence of cancer, death, and major health outcomes (e.g., cardiovascular disease, diabetes) through routine ascertainment of new cases from the population-based Shanghai Cancer Registry and Shanghai Vital Statistics Units, and annual visits to all known surviving cohort members. In addition to cohort analyses to examine the impact of cigarette smoking, alcohol intake, and certain dietary factors on mortality and morbidity, a series of nested case-control studies has been conducted to further elucidate the role o diet-related factors using biomarkers as more specific and objective measures for exposure in the etiology of cancer. Furthermore, the interplay of genetic and dietary factors in influencing cancer risk has been examined among the cohort participants.

This prospective cohort study has contributed a wealth of knowledge on the role of diet-related and other environmental exposures, as well as genetic factors in the etiology of cancer. More than 35 peer-reviewed articles have emanated from this study. Significant scientific contributions include the:

• first direct evidence that aflatoxin is a human hepatocarcinogen, and the evidence of a strong synergistic effect of urinary aflatoxin biomarkers and chronic infection with hepatitis B virus on liver cancer risk (Lancet. 1992 Apr 18;339(8799):943-6; Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):3-10);
• first evidence that circulating testosterone levels predict liver cancer risk but only among carriers of hepatitis B virus (Int J Cancer. 1995 Nov 15;63(4):491-3);
• first evidence in a non-Occidental population that smoking is a strong predictor of overall mortality and cancer mortality (JAMA. 1996 Jun 5;275(21):1646-50);
• first demonstration in a non-Occidental population that moderate alcohol intake is associated with the lowest risk of overall mortality (i.e., an U-shaped drinking-mortality curve) (BMJ. 1997 Jan 4;314(7073):18-23);
• first evidence that a history of hypertension is a strong predictor for risk of stroke mortality in this high-risk Chinese population (Circulation. 1997 Jul 1;96(1):50-5;
• first demonstration in a non-Occidental population that either low or high body mass index (BMI) is associated with increased total mortality (a U-shaped BMI-mortality curve) (Int J Epidemiol. 1998 Oct;27(5):824-32);
• first serologic evidence in a non-Occidental population that H. pylori infection predicts gastric cancer risk (Cancer Epidemiol Biomarkers Prev. 1999 Jul;8(7):621-4);
• first direct evidenc that dietary isothiocyanates (ITCs) protect against the development of lung cancer in humans. The chemopreventive effect is modified by genetic variation in glutathione S-transferases (GSTs) that favor rapid elimination of these compounds (Lancet. 2000 Aug 26;356(9231):724-9);
• first evidence in a non-Occidental population that intake of fish or omega-3 fatty acids is associated with reduced risk of fatal myocardial infarction (Am J Epidemiol. 2001 Nov 1;154(9):809-16);
• first evidence of an inverse relationship between prediagnostic serum beta-cryptoxanthin level and lung cancer risk in smokers (Cancer Epidemiol Biomarkers Prev. 2003 Sep;12(9):890-8);
• first demonstration in a non-Occidental population that insulin-like growth factors (IGF) and their binding proteins are associated with risk of colorectal and lung cancers (Br J Cancer. 2001 Nov 30;85(11):1695-9; J Natl Cancer Inst. 2002 May 15;94(10):749-54);
• first demonstration that prediagnostic serum beta-carotene and vitamin C levels are inversely associated with gastric cancer risk (Cancer Epidemiol Biomarkers Prev. 2004 Nov;13(11 Pt 1):1772-80);
• first unequivocal evidence that serum retinol, but not carotenoids, is associated with reduced risk of liver cancer (J Natl Cancer Inst. 2006 Apr 5;98(7):482-90);
• first evidence that prediagnostic urinary levels of tea polyphenols are inversely related to risk of esophageal, gastric, and colorectal cancers (Carcinogenesis. 2002 Sep;23(9):1497-503; Int J Cancer. 2007 Mar 15;120(6):1344-50.)
• first demonstration that urinary total isothiocyanates (ITCs) are associated with reduced risk of colon and gastric cancer, especially for individuals with the deletion polymorphisms in glutathione S-transferases M1 and T1 genes (Cancer Epidemiol Biomarkers Prev 2008 Jun;17(6):1354-9; Int J Cancer. 2009 Dec 1;125(11):2652-9); and
• first report on a direct link between tobacco carcinogen NNK and lung cancer in smokers (Cancer Research. 2009 Apr 1; 69(7): 2990-5).