Carcinogenesis Advance Access published online on January 18, 2007
Carcinogenesis, 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
1 Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China
2 Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China
* To whom correspondence and reprints should be addressed: Xing Xie, Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Xueshi Rd #2, Hangzhou, 310006, China. Fax: 86-571-87061878. E-mail: 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 intraepithelial 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) 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% CI = 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.
Key Words: MGMT • single nucleotide polymorphism • cervical carcinoma • DNA repair
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