Willems Petra, De Ruyck Kim, Van den Broecke Rudy, Makar Amin, Perletti Gianpaolo, Thierens Hubert, Vral Anne
Department of Basic Medical Science, Ghent University, 9000 Ghent, Belgium.
J Cancer Res Clin Oncol. 2009 Sep;135(9):1159-68. doi: 10.1007/s00432-009-0556-x. Epub 2009 Feb 15.
Polymorphisms in double strand break repair genes could be involved in genetic breast cancer predisposition as enhanced chromosomal radiosensitivity is a hallmark for breast cancer. Previously, the c.-1310 C>G SNP, located in the Ku70 promoter, showed a significant odds ratio (OR) of 1.85 (P = 0.048) in sporadic, but not familial breast cancer patients, indicating that other factors besides genetic aptitude influence this association. As breast epithelium is exposed to endogenous oxidative stress through oestrogen exposure, the influence of hormone exposure was further examined.
A significant OR (1.69, P = 0.017) was found for an enlarged patient population through PCR-RFLP assays in a case-control study in a Belgian population. After dividing the patient population according to oestrogen exposure, high and significant ORs were seen for patients with a longer oestrogen exposure (late age at menopause: OR = 1.96, P = 0.029).
These results show that the variant allele of c.-1310 C>G, located in the Ku70 promoter, is a risk allele for breast cancer. Furthermore, the association of the c.-1310 C>G SNP with breast cancer risk was stronger in women with a long oestrogen exposure.
双链断裂修复基因中的多态性可能与遗传性乳腺癌易感性有关，因为增强的染色体放射敏感性是乳腺癌的一个标志。此前，位于Ku70启动子区的c.-1310 C>G单核苷酸多态性（SNP）在散发性乳腺癌患者中显示出显著的优势比（OR）为1.85（P = 0.048），但在家族性乳腺癌患者中未显示，这表明除了遗传倾向外，其他因素也会影响这种关联。由于乳腺上皮通过雌激素暴露会受到内源性氧化应激的影响，因此进一步研究了激素暴露的影响。
在比利时人群的一项病例对照研究中，通过聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对更多患者群体进行检测，发现了显著的OR（1.69，P = 0.017）。根据雌激素暴露情况对患者群体进行划分后，雌激素暴露时间较长的患者（绝经年龄较晚：OR = 1.96，P = 0.029）出现了高且显著的OR。
这些结果表明，位于Ku70启动子区的c.-1310 C>G变异等位基因是乳腺癌的一个风险等位基因。此外，c.-1310 C>G SNP与乳腺癌风险的关联在雌激素暴露时间长的女性中更强。
