Single-nucleotide polymorphisms in BER and HRR genes, XRCC1 haplotypes and breast cancer risk in Caucasian women

• DOI: 10.1007/s00432-010-0791-1
• Publication Date: 2010-02-05T06:58:19Z
• Authors: Silvia Sterpone; Valeria Mastellone; Luca Padua; Flavia Novelli; Clarice Patrono; Tommaso Cornetta; Daniela Giammarino; Vittorio Donato; Antonella Testa; Renata Cozzi
• Keywords: Adult; DNA repair; Single-nucleotide polymorphisms; XRCC1 haplotype ; BASE-EXCISION-REPAIR; SUSCEPTIBILITY; DNA repair; Breast Neoplasms; Middle Aged; Single-nucleotide polymorphisms; Polymorphism, Single Nucleotide; White People; DNA Glycosylases; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; Breast cancer; X-ray Repair Cross Complementing Protein 1; 0302 clinical medicine; Haplotypes; Risk Factors; Humans; XRCC1 haplotype; Female; Genetic Predisposition to Disease; breast cancer; dna repair; single-nucleotide polymorphisms; xrcc1 haplotype; Aged

This study aimed to assess whether haplotypes in XRCC1 and SNPs in OGG1 and XRCC3 were associated with an increased risk of developing breast cancer (BC) and early adverse reactions after radiotherapy.43 Italian breast cancer patients and 31 healthy controls were genotyped for XRCC1(-77T-->C,194,399), OGG1-326 and XRCC3-241 by RFLP-PCR.XRCC1-77T-->C, XRCC1-194, OGG1 and XRCC3 were not associated with BC. On the contrary, we found a significant association (p or=3 SNPs [OR = 2.72 (0.99-7.39), p = 0.04].In our study, the 399-Gln allele of XRCC1 increased significantly the risk of BC and it may act as a dominant allele [Arg/Arg vs. (Gln/Gln + Arg/Gln), OR = 4.67 (95% CI 1.65-13.23), p = 0.005]. The combination of variant alleles at codon 399 and in position -77 could affect XRCC1 protein activity, impairing genome integrity and promoting cancer occurrence. Also, the number of SNPs in several genes involved in BER and HRR mechanisms made higher the risk of sporadic BC. We can conclude that genetic variants in multiple repair pathways may have a joint or additive effect in cancer risk.