Carcinogenesis Advance Access published online on June 15, 2006
Carcinogenesis, doi:10.1093/carcin/bgl099
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1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA; The Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA
* To whom correspondence should be addressed. Cigarette smoking is inversely associated with endometrial cancer risk. Smoking is proposed to decrease risk, in large part, through its anti-estrogenic effects in the uterus. In addition, cigarette smoke is a major source of alkylation damage. The O6-methylguanine DNA methyltransferase (MGMT) gene is responsible for repairing alkylation DNA damage and also has a role in inhibiting estrogen receptor-mediated cell proliferation. Because of MGMT's dual functions, it is a strong candidate gene for endometrial cancer. We assessed the two functional polymorphisms, the Leu84Phe and Ile143Val, in relation to endometrial cancer risk in a nested case-control study within the Nurses' Health Study (cases=456, controls=1134). Compared with the 84Leu/Leu genotype, the Phe carriers had a significantly decreased risk of endometrial cancer (odds ratio (OR), 0.72; 95% confidence interval (CI), 0.53-0.96). We did not observe an association between the Ile143Val polymorphism and endometrial cancer risk overall. We observed a significant multiplicative interaction between the Ile143Val polymorphism and pack-years of smoking on endometrial cancer risk (P, interaction, 0.04); the inverse association of pack-years with endometrial cancer risk was limited to the 143Val carriers (P, trend, 0.01). Compared with women who had the Ile/Ile genotype and never smoked, the 143Val carriers who had more than 30 pack-years of smoking had a significantly decreased risk of endometrial cancer (OR, 0.41; 95%CI, 0.19-0.86). These data suggest that these two polymorphisms may influence endometrial cancer risk.
Received March 18, 2006
Revised June 1, 2006
Accepted June 3, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Polymorphisms in O6-methylguanine DNA methyltransferase and endometrial cancer risk
Jiali Han 1 *,
Susan E. Hankinson 2,
and
Immaculata De Vivo 3
2 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA
3 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA; The Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA
Jiali Han, E-mail: jiali.han{at}channing.harvard.edu
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