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Grant Details

Grant Number: 5R01CA114421-06 Interpret this number
Primary Investigator: Risch, Harvey
Organization: Yale University
Project Title: Case Control Study of Pancreas Cancer in Shanghai, China
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): In the US in 2005, about 32,200 individuals will be diagnosed with pancreas cancer, and nearly that number will die from it, making it the 4th most frequent cause of cancer death, after lung, breast/prostate and colorectal cancer. Over the lifetime, more than 1% of the population is affected. Survival with this cancer is dismal: one year about 20-30%, and 5-year, about 5%. Compared to the US, pancreas cancer is less frequent in China (and gastric cancer more frequent), yet risk factors for these cancers?gastric colonization by Helicobacter pylori, cigarette smoking, nitrite or A/-nitrosamine intake?are more prevalent in China. We recently developed a new hypothesis on the etiology of pancreatic cancer, concerning A/-nitrosamine exposures and chronic excess gastric acidity, the latter typically resulting from Helicobacter colonization, modulated by host inflammatory cytokine polymorphisms. For individuals with H. pylori, these cytokine variants act as a genetic switch, increasing risk of pancreas cancer and decreasing risk of gastric cancer, or vice versa. Ethnic frequency differences in carriage of these cytokine variants likely explains the lower risk of pancreas cancer in China compared to the US. We propose to conduct, in urban Shanghai, China, a population-based case- control study of Helicobacter, genetic, and dietary factors. In total, 1,000 pancreas-cancer cases aged 35-79 years will be identified prospectively via the ultra-rapid case accession program of the Shanghai Cancer Institute. About 1,000 randomly selected population controls will be frequency matched to the cases by age and gender, and will be identified by use of the Shanghai Residents Registry. All subjects will be interviewed in person by trained interviewers using a standardized, structured questionnaire that will include tobacco use, a standard food-frequency questionnaire for the local Chinese diet, and other factors specific to our hypotheses. A small blood sample will be drawn to test for colonization by H. pylori, and for DMA polymorphisms in inflammatory cytokine genes relevant to our hypotheses. Average daily intake of nitrite, A/-nitroso compounds, and other dietary constituents and nutrients will be calculated from the diet histories, and uni- and multivariate analyses will be used to estimate relative risks for comparison of the cases with the controls. The Helicobacter, genetic and dietary factors will also be compared to the same variables in our ongoing similar population-based pancreas cancer study in Connecticut. Understanding the etiology of pancreas cancer will help to provide direction for modifying individual behaviors related to risk. In addition to reduction of cigarette smoking, Helicobacter and dietary factors are modifiable and could be involved in a program to reduce risk of pancreas cancer.

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Publications

Helicobacter pylori seropositivities and risk of pancreatic carcinoma.
Authors: Risch HA, Lu L, Kidd MS, Wang J, Zhang W, Ni Q, Gao YT, Yu H
Source: Cancer Epidemiol Biomarkers Prev, 2014 Jan;23(1), p. 172-8.
EPub date: 2013 Nov 14.
PMID: 24234587
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Dietary energy density is positively associated with risk of pancreatic cancer in urban Shanghai Chinese.
Authors: Wang J, Zhang W, Sun L, Yu H, Ni QX, Risch HA, Gao YT
Source: J Nutr, 2013 Oct;143(10), p. 1626-9.
EPub date: 2013 Jul 31.
PMID: 23902959
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Re-evaluation of ABO gene polymorphisms detected in a genome-wide association study and risk of pancreatic ductal adenocarcinoma in a Chinese population.
Authors: Xu HL, Cheng JR, Zhang W, Wang J, Yu H, Ni QX, Risch HA, Gao YT
Source: Chin J Cancer, 2014 Feb 5;33(2), p. 68-73.
EPub date: 2013 Jul 2.
PMID: 23816557
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ABO blood group and risk of pancreatic cancer: a study in Shanghai and meta-analysis.
Authors: Risch HA, Lu L, Wang J, Zhang W, Ni Q, Gao YT, Yu H
Source: Am J Epidemiol, 2013 Jun 15;177(12), p. 1326-37.
EPub date: 2013 May 6.
PMID: 23652164
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Green tea drinking and risk of pancreatic cancer: a large-scale, population-based case-control study in urban Shanghai.
Authors: Wang J, Zhang W, Sun L, Yu H, Ni QX, Risch HA, Gao YT
Source: Cancer Epidemiol, 2012 Dec;36(6), p. e354-8.
EPub date: 2012 Sep 1.
PMID: 22944495
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ABO blood group, Helicobacter pylori seropositivity, and risk of pancreatic cancer: a case-control study.
Authors: Risch HA, Yu H, Lu L, Kidd MS
Source: J Natl Cancer Inst, 2010 Apr 7;102(7), p. 502-5.
EPub date: 2010 Feb 24.
PMID: 20181960
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Etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity.
Authors: Risch HA
Source: J Natl Cancer Inst, 2003 Jul 2;95(13), p. 948-60.
PMID: 12837831
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