A polymorphism in the promoter region of Ku70/XRCC6, associated with breast cancer risk and oestrogen exposure

作者：Willems Petra; De Ruyck Kim; Van den Broecke Rudy; Makar Amin; Perletti Gianpaolo; Thierens Hubert; Vral Anne^*

来源：Journal of Cancer Research and Clinical Oncology, 2009, 135(9): 1159-1168.

DOI：10.1007/s00432-009-0556-x

• Double strand break (DSB) repair
• Non-homologous end-joining (NHEJ)
• Ku70/XRCC6
• Breast cancer
• Hormone exposure
• Single nucleotide polymorphism (SNP)

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.

• 出版日期2009-9