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

Silvia Sterpone, Valeria Mastellone, Luca Padua, Flavia Novelli, Clarice Patrono, Tommaso Cornetta, Daniela Giammarino, Vittorio Donato, Antonella Testa, Renata Cozzi

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Purpose: 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. Methods: 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. Results: XRCC1-77T→C, XRCC1-194, OGG1 and XRCC3 were not associated with BC. On the contrary, we found a significant association (p ≤ 0.05) between breast cancer occurrence and XRCC1-399. The haplotype (H3) containing the variant allele at codon 399, together with variant C allele in the promoter and wild-type G allele at codon 194 was associated with higher BC risk [p = 0.009, OR = 7.04(1.63-30)]. The probability for developing this tumor was also increased by the number of SNPs in different genes. We found a significantly higher BC risk in subjects with ≥3 SNPs [OR = 2.72 (0.99-7.39), p = 0.04]. Conclusion: 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. © 2010 Springer-Verlag.
Original languageEnglish
Pages (from-to)631 - 636
Number of pages6
JournalJournal of Cancer Research and Clinical Oncology
Issue number4
Publication statusPublished - Apr 2010
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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