An intronic polymorphism associated with increased XRCC1 expression, reduced apoptosis and familial breast cancer

作者：Bu Dawei; Tomlinson Gail; Lewis Cheryl M; Zhang Cindy; Kildebeck Eric; Euhus David M^*

来源：Breast Cancer Research and Treatment, 2006, 99(3): 257-265.

DOI：10.1007/s10549-006-9210-3

• single nucleotide polymorphisms
• DNA repair
• breast neoplasms
• XRCC1
• apoptosis
• intron
• PLAG1

XRCC1 coordinates the activities of DNA polymerasc-beta and DNA ligase for base excision repair of oxidative DNA damage. In addition, there is some evidence that XRCC1 is a negative regulator of apoptosis. Single nucleotide polymorphisms in XRCC1 have been inconsistently associated with breast cancer risk. We evaluated XRCC1 gene expression in breast cancer cell lines and carcinogen-induced apoptosis in benign breast epithelial cells in relation to XRCC1 genotypes. XRCC1 IVS10+141G > A was associated with increased expression of XRCC1 mRNA and protein, and reduced apoptosis in response to benzo-[a]-pyrene or ionizing radiation, but XRCC1 R399Q was not. These genotypes were also assessed in a clinic-based sample that included 190 breast cancer patients with a family history of breast cancer and 95 controls with no family history of breast cancer. Heterozygous XRCC1 IVS10+141G > A was associated with an increased breast cancer risk (O.R. = 1.7, 95% C.I. 1.016-2.827, P = 0.04) as was homozygous XRCC1 IVS10+141G > A (O.R. = 4.7, 95% C.I. 1.028-21.444, P = 0.03). XRCC1 R399Q was not associated with breast cancer (O.R. 1.00, 95% C.I. 0.61-1.64). The XRCC1 IVS10+141G > A locus is centered in a sequence that is nearly identical to the consensus binding site for the PLAG1 transcription factor. XRCC1 IVS10+141G > A is an intronic polymorphism that is associated with XRCC1 expression, apoptosis and familial breast cancer. It may occur within an intronic regulatory sequence.

• 出版日期2006-10