Polymorphisms of genes in the inflammatory pathway and the risk of gallstones and biliary tract cancer: a population-based study

Hsing, Ann W.; Rosenberg, Philip; Chen, Bingshu; Chen, Jinbo; Rashid, Asif; Deng, Jie; Cohen-Webb, Hope; Sakoda, Lori; Shen, Ming-Chang; Andreotti, Gabriella; Wang, Bin-Sheng; Han, Tain-Quan; Zhang, Bai-He; Yeager, Meredith; Welch, Robert; Chanock, Stephan; Fraumeni, Joseph; Gao, Yu-Tang

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Epidemiology 7: Perspectives of Susceptibility Genes in Families and Populations| April 15 2006

Polymorphisms of genes in the inflammatory pathway and the risk of gallstones and biliary tract cancer: a population-based study

Ann W. Hsing;

Ann W. Hsing

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Philip Rosenberg;

Philip Rosenberg

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Bingshu Chen;

Bingshu Chen

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Jinbo Chen;

Jinbo Chen

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Asif Rashid;

Asif Rashid

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Jie Deng;

Jie Deng

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Hope Cohen-Webb;

Hope Cohen-Webb

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Lori Sakoda;

Lori Sakoda

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Ming-Chang Shen;

Ming-Chang Shen

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Gabriella Andreotti;

Gabriella Andreotti

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Bin-Sheng Wang;

Bin-Sheng Wang

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Tain-Quan Han;

Tain-Quan Han

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Bai-He Zhang;

Bai-He Zhang

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Meredith Yeager;

Meredith Yeager

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Robert Welch;

Robert Welch

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Stephan Chanock;

Stephan Chanock

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Joseph Fraumeni, Jr.;

Joseph Fraumeni, Jr.

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Yu-Tang Gao

National Cancer Institute, Rockville, MD, MD Anderson Cancer Center, Houston, TX, Shanghai Cancer Institute, Shanghai, China, Westat, Rockville, MD, Shanghai Tumor Hospital, Shanghai, China, Zhong Shan Hospital, Fudan University, Shanghai, China, Rui-jian Hospital, Shanghai, China, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, Core Genotyping Facility, National Cancer Institute, Rockville, MD

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Author & Article Information

Online ISSN: 1538-7445

Print ISSN: 0008-5472

American Association for Cancer Research

2006

Cancer Res (2006) 66 (8_Supplement): 699.

Abstract

2969

Abundant clinical data suggest a critical role of chronic inflammation in the pathogenesis of gallstones (cholelithiasis) and of biliary tract cancer (including cancers of the gallbladder, extrahepatic bile duct, and ampulla of Vater). Since cholecystitis, cholelithiasis, and cholangitis have been linked to excess risk of biliary tract cancer, it seems likely that chronic inflammation of the biliary tree, often in association with gallstones, plays an important role in the pathogenesis of biliary tract cancer and that individuals with certain variants of genes in the inflammation pathway may have an increased susceptibility to cancer. Using a pathway approach, we examined 57 single nucleotide polymorphisms (SNPs) in 14 genes in the inflammatory pathway, including ILs (IL1-alpha, IL1-beta, IL4, IL5, IL6, IL8, IL10, IL13), TNF-α, RNASEL, VEGF, VCAM1, MnSOD2, and COX2, in a population-based case-control study of biliary tract cancer in Shanghai, China. Although the roles of these genes have not been investigated in biliary tract cancer, many of them have been linked to other cancers that are closely related to inflammation. Genomic DNA from 522 biliary tract cancer cases (238 gallbladder cancers, 128 bile duct cancers, 56 ampulla of Vater cancers), 782 population controls, and 889 biliary stone cases was purified from buffy coat samples and genotyped at the NCI Core Genotyping Facility using the Taqman assay. Concordance of genotyping results on duplicate samples was over 99%. Despite the strong biological plausibility that chronic inflammation may be a key factor in the pathogenesis of gallstones and biliary tract cancer, of the 57 SNPs examined, only a few were associated with gallstones and biliary tract cancer, with inconsistent patterns in men and women. For example, 4 SNPs in the TNF-alpha, MnSOD2, and COX2 genes were associated with an increased risk of biliary stones in men, while 3 SNPs in the MnSOD2, VEGF, and COX2 genes were associated with bile duct cancer in men and one SNP in the RNASEL gene with a higher risk of bile duct cancer in women. Preliminary results from this population-based study suggest that chronic inflammation may be associated with gallstones and biliary tract cancer in a complex manner that involves an interplay among multiple susceptibility genes, gender-related exposures, and gallstones or cholangitis. Larger studies with a more comprehensive genomic approach are needed to dissect the relationships among these putative factors and clarify the mechanisms involved.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]

American Association for Cancer Research

2006

Polymorphisms of genes in the inflammatory pathway and the risk of gallstones and biliary tract cancer: a population-based study

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Polymorphisms of genes in the inflammatory pathway and the risk of gallstones and biliary tract cancer: a population-based study

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