Polymorphisms in O6-methylguanine DNA methyltransferase and endometrial cancer risk

Jiali Han, Susan E. Hankinson, Immaculata De Vivo

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 >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.

Original languageEnglish (US)
Pages (from-to)2281-2285
Number of pages5
JournalCarcinogenesis
Volume27
Issue number11
DOIs
StatePublished - Nov 15 2006
Externally publishedYes

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Methyltransferases
Endometrial Neoplasms
DNA
Smoking
Alkylation
Case-Control Studies
Odds Ratio
Genotype
Confidence Intervals
O-(6)-methylguanine
Smoke
Tobacco Products
Estrogen Receptors
Genes
DNA Damage
Uterus
Estrogens
Nurses
Cell Proliferation
Health

ASJC Scopus subject areas

  • Cancer Research

Cite this

Polymorphisms in O6-methylguanine DNA methyltransferase and endometrial cancer risk. / Han, Jiali; Hankinson, Susan E.; De Vivo, Immaculata.

In: Carcinogenesis, Vol. 27, No. 11, 15.11.2006, p. 2281-2285.

Research output: Contribution to journalArticle

Han, Jiali ; Hankinson, Susan E. ; De Vivo, Immaculata. / Polymorphisms in O6-methylguanine DNA methyltransferase and endometrial cancer risk. In: Carcinogenesis. 2006 ; Vol. 27, No. 11. pp. 2281-2285.
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