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

Abstract

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.

• Authors: Jiali Han, Christopher Haiman, Tianhua Niu, Qun Guo, David G Cox, Walter C Willett, Susan E Hankinson, David J Hunter
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 115 Issue 3 Pg. 613-22 (Jun 2009) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 18551366 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• DNA-Binding Proteins
• X-ray repair cross complementing protein 3
• xeroderma pigmentosum group F protein
• DNA Repair Enzymes

Topics

• Adult
• Breast Neoplasms (genetics, pathology)
• Case-Control Studies
• Cohort Studies
• DNA Repair
• DNA Repair Enzymes (genetics)
• DNA-Binding Proteins (genetics)
• Female
• Humans
• Middle Aged
• Neoplasm Staging
• Nurses
• Odds Ratio
• Polymorphism, Single Nucleotide (genetics)
• Premenopause
• Prognosis
• Prospective Studies