Department of Biology, Rome Tre University, Rome, Italy.
J Cancer Res Clin Oncol. 2010 Apr;136(4):631-6. doi: 10.1007/s00432-010-0791-1. Epub 2010 Feb 6.
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= 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 >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.
本研究旨在评估 XRCC1 中的单倍型和 OGG1 及 XRCC3 中的 SNP 是否与乳腺癌（BC）风险增加以及放疗后早期不良反应相关。
采用 RFLP-PCR 技术对 43 名意大利乳腺癌患者和 31 名健康对照者的 XRCC1(-77T-->C，194，399)、OGG1-326 和 XRCC3-241 进行基因分型。
XRCC1-77T-->C、XRCC1-194、OGG1 和 XRCC3 与 BC 无关。相反，我们发现 XRCC1-399 与乳腺癌的发生存在显著相关性（p≤0.05）。在密码子 399 处携带变异等位基因的单倍型（H3），与启动子处的变异 C 等位基因和密码子 194 处的野生型 G 等位基因一起，与更高的 BC 风险相关[p=0.009，OR=7.04（1.63-30）]。不同基因中的 SNP 数量也增加了发生这种肿瘤的概率。我们发现，携带≥3 个 SNP 的个体发生 BC 的风险显著增加[OR=2.72（0.99-7.39），p=0.04]。
在本研究中，XRCC1 的 399-Gln 等位基因显著增加了 BC 的风险，可能起显性等位基因的作用[Arg/Arg 与（Gln/Gln+Arg/Gln）相比，OR=4.67（95%CI 1.65-13.23），p=0.005]。密码子 399 处和 -77 位的变异等位基因的组合可能会影响 XRCC1 蛋白的活性，损害基因组的完整性并促进癌症的发生。此外，BER 和 HRR 机制中多个基因的 SNP 数量增加了散发型 BC 的风险。我们可以得出结论，多个修复途径中的遗传变异可能在癌症风险中具有联合或相加的作用。
