Carcinogenesis Advance Access originally published online on March 17, 2005
Carcinogenesis 2005 26(7):1280-1284; doi:10.1093/carcin/bgi071
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Carcinogenesis vol.26 no.7 © Oxford University Press 2005; all rights reserved.
LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China
1 Beijing Institute for Cancer Research, School of Oncology, Peking University, Beijing 100034, China, 2 Chinese National Human Genome Center, Beijing 100069, 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 Department of Cell Biology and Human Genetics, Peking University, Beijing 100086, China and 6 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 at: Department of Genetics, Beijing Institute for Cancer Research, School of Oncology, Peking University, No. 1 Da Hong Luo Chang Street, Western District, Beijing 100034, China. Tel: 8610 66162006; Fax: 8610 66175832; Email: keyang{at}mx.cei.gov.cn
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 prevalence of esophageal carcinoma. 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. 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. The TAP2 codons 379 isoleucine carriers and LMP7 codons 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 codons 145 and the isoleucine at TAP2 codons 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). LMP7/TAP2 haplotype C may act as the risk factor in esophageal carcinoma development and it may influence the tumorigenesis in HPV infected individuals.
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