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    Breast Cancer Res Treat. 2009 Jun;115(3):613-22. Epub 2008 Jun 13.

    Genetic variation in DNA repair pathway genes and premenopausal breast cancer risk.

    Han J, Haiman C, Niu T, Guo Q, Cox DG, Willett WC, Hankinson SE, Hunter DJ.

    Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Ave., Boston, MA 02115, USA. jiali.han@channing.harvard.edu

    PURPOSE: We comprehensively evaluated genetic variants in DNA repair genes with premenopausal breast cancer risk. METHODS: In this nested case-control study of 239 prospectively ascertained premenopausal breast cancer cases and 477 matched controls within the Nurses' Health Study II, we evaluated 1,463 genetic variants in 60 candidate genes across five DNA repair pathways, along with DNA polymerases, Fanconi Anemia complementation groups, and other related genes. RESULTS: Four variants were associated with breast cancer risk with a significance level of <0.01; two in the XPF gene and two in the XRCC3 gene. An increased risk was found in those harboring a greater number of missense putative risk alleles (a priori defined in an independent study) in the non-homologous end-joining (NHEJ) repair pathway of double-strand breaks (odds ratio (OR) per risk allele, 1.37 (95% confidence interval (CI), 1.03-1.82), P trend, 0.03). CONCLUSIONS: This study implicates variants of genes in the double-strand break repair pathway in the etiology of premenopausal breast cancer.

    PMID: 18551366 [PubMed - indexed for MEDLINE]

    PMCID: 2693208

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