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Carcinogenesis Advance Access originally published online on January 18, 2007
Carcinogenesis 2007 28(6):1314-1322; doi:10.1093/carcin/bgm003
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Amino acid substitution polymorphisms of the DNA repair gene MGMT and the susceptibility to cervical carcinoma

Jinyang Huang, Feng Ye1, Huaizeng Chen, Weiguo Lu1 and Xing Xie1,*

Women's Reproductive Health Laboratory of Zhejiang Province
1 Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China

* To whom correspondence should be addressed. Fax: +86 571 87061878; Tel: +86 571 87061501; Email: xiex{at}mail.hz.zj.cn

In the current study, we examined the association between polymorphisms in the O6-methylguanine-DNA methyltransferase gene (MGMT) and the risk for cervical carcinoma. We prospectively selected 1012 patients, including 539 with carcinoma and 473 with cervical intra-epithelial neoplasia and 800 healthy women from five hospitals in Zhejiang Province, China. Three single-nucleotide polymorphisms (Leu84Phe, Ile143Val and Lys178Arg) were genotyped, and their association with other epidemiological risk factors was examined. Compared with the MGMT Lys178Lys (AA) or Ile143Ile (AA) genotypes, women homozygous for the Arg178Arg (GG) or Val 143Val (GG) genotypes had a significantly increased risk for cervical carcinoma both in the overall carcinoma group and in the high-risk human papillomavirus-positive group. Compared with using Leu84Leu (CC), Phe84Phe (TT) and Leu84Phe (CT) which did not increase the risk for cervical carcinoma. In addition, using 84Leu (C)-143Ile (A)-178Lys (A) as reference, women carrying 84Phe (T)-143Val (G)-178Arg (G) had a 1.87-fold higher risk for cervical carcinoma (95% confidence interval 1.07–3.27). Similar results were observed for squamous cell carcinomas. The effect of the combination of Arg178Arg (GG) and Lys178Arg (AG) genotypes and the 84Phe (T)-143Val (G)-178Arg (G) haplotype was more pronounced in women infected with high-risk human papillomavirus, an early onset of sexual activity, multiple sexual partners, an early age of the first full-term pregnancy and high parity. These findings suggest that polymorphism in MGMT increases the susceptibility of women to cervical carcinoma, especially in those with high-risk sexual and reproductive histories.

Abbreviations: CI, confidence interval; CIN, cervical intra-epithelial neoplasia; HR-HPV, high-risk human papillomavirus; MGMT, O6-methylguanine-DNA-methyltransferase gene; OR, odds ratio; PCR, polymerase chain reaction; SNP, single-nucleotide polymorphism

Received July 19, 2006; revised December 6, 2006; accepted January 9, 2007.


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