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Carcinogenesis Advance Access published online on March 17, 2005
Carcinogenesis, doi:10.1093/carcin/bgi071
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received December 30, 2004
Revised March 2, 2005
Accepted March 8, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China

Bangwei Cao 1, Xiuyun Tian 2, Yong Li 2, Pingwei Jiang 3, Tao Ning 2, Haiping Xing 4, Yiqiang Zhao 5, Chunfeng Zhang 6, Xiaotian Shi 4, Dafang Chen 6, Yan Shen 7, and Yang Ke 5*

1 Beijing Institute for Cancer Research, School of Oncology, Peking University, Beijing 100034, China; Chinese National Human Genome Center, Beijing 100069, China; Xuzhou No.1 People's Hospital, Xuzhou City, Jiangsu Province 221002, China
2 Beijing Institute for Cancer Research, School of Oncology, Peking University, Beijing 100034, China
3 Xuzhou No.1 People's Hospital, Xuzhou City, Jiangsu Province 221002, China
4 Anyang Tumor Hospital, Anyang City, Henan Province 455000, China
5 Beijing Institute for Cancer Research, School of Oncology, Peking University, Beijing 100034, China; Chinese National Human Genome Center, Beijing 100069, China
6 Department of Cell Biology and Human Genetics, Peking University, Beijing 100086, China
7 Chinese National Human Genome Center, Beijing 100069, China; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing 100069, China

* To whom correspondence should be addressed.
Yang Ke, E-mail: keyang{at}mx.cei.gov.cn


  Abstract

Background: Esophageal carcinoma is characterized by a widely ranged incidence variation among the different geographic regions. Anyang is a county in Henan Province of North China with the highest esophageal carcinoma prevalence. Human papillomavirus (HPV) infection has been linked to the etiology of esophageal cancer in this area. In this study we investigated correlations of the polymorphisms at low molecular weight polypeptide (LMP) and transporters with antigen processing (TAP) genes, with the risk of esophageal carcinoma. Methods: DNA extracted from either tumor specimens or esophageal epithelial cells was used to test HPV infection. Peripheral blood lymphocyte DNA was used for LMP/TAP genotyping. Polymerase chain reaction was performed to analyze HPV infection and LMP/TAP gene polymorphisms. The combined effect of LMP/TAP gene polymorphisms and HPV infection on esophageal carcinoma was analyzed by using unconditional logistic regression models. Results: The TAP2 codon 379 isoleucine carriers and LMP7 codon 145 lysine carriers were found to be more susceptible to esophageal carcinoma (OR=2.74, 95%CI=1.15-6.49, P=0.023 for TAP2; OR=2.19, 95%CI=1.09-4.37, P=0.027 for LMP7). Patients carrying homozygous LMP7/TAP2 haplotype C, which contained the glutamine at LMP7 codon 145 and the isoleucine at TAP2 codon 379, were more prone to develop esophageal carcinoma (OR=2.96, 95%CI=1.13-7.81, P=0.027). An additive effect on the risk of esophageal carcinoma development was found among individuals carrying LMP7/TAP2 haplotype C and infected by HPV (OR= 4.33, 95% CI=2.53-7.42, P<0.0001). Conclusions: LMP7/TAP2 haplotype C may act as the risk factor in esophageal carcinoma development and it may influence the tumorigenesis in HPV infected individuals.

Keywords: esophageal carcinoma; LMP/TAP; polymorphism; genetic susceptibility.
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