Polymorphisms in O6-methylguanine DNA methyltransferase and breast cancer risk

Jiali Han, Gregory J. Tranah, Susan E. Hankinson, Leona D. Samson, David J. Hunter

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

OBJECTIVE: Endogenous and exogenous estrogens influence breast cancer risk by interacting with estrogen receptor (ER). The O-methylguanine DNA methyltransferase (MGMT) gene has a dual role in repairing alkylation damage and in inhibiting ER-mediated cell proliferation. We assessed the two MGMT polymorphisms, Leu84Phe and Ile143Val, with breast cancer risk. We also evaluated the potential interactions between the two polymorphisms and estrogen-related risk factors and cigarette smoking on breast cancer risk. METHODS: We conducted a nested case-control study within the Nurses' Health Study (1311 cases, 1760 controls). RESULTS: Compared with the 84Leu/Leu genotype, the Phe/Phe genotype had a multivariate odds ratio (OR) of 1.68 (95% confidence interval (CI), 0.98-2.88). This positive association was magnified among postmenopausal women with body mass index>25 (OR, 3.01; 95% CI, 1.30-6.94), those in the highest tertile of pre-diagnostic plasma endogenous estradiol levels (Phe carriers versus non-carriers, OR, 2.42; 95% CI, 1.49-3.94), non-current postmenopausal hormone users (OR, 2.60; 95% CI, 1.19-5.64), and possibly estrogen receptor-positive cases (OR, 1.82; 95% CI, 0.99-3.35). We did not observe a main effect of the Ile143Val polymorphism or its interactions with these factors. No interaction was observed between either of the polymorphisms and cigarette smoking on breast cancer risk. CONCLUSIONS: These data suggest that the Leu84Phe polymorphism affect the capacity of MGMT to inhibit estrogen receptor-mediated cell proliferation and is associated with breast cancer risk.

Original languageEnglish (US)
Pages (from-to)469-474
Number of pages6
JournalPharmacogenetics and Genomics
Volume16
Issue number7
DOIs
StatePublished - Jul 2006
Externally publishedYes

Keywords

  • Breast cancer
  • Estrogen
  • MGMT

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Polymorphisms in O<sup>6</sup>-methylguanine DNA methyltransferase and breast cancer risk'. Together they form a unique fingerprint.

  • Cite this