Association between polymorphisms at promoters of XRCC5 and XRCC6 genes and risk of breast cancer

Abstract

Variation in DNA repair genes is one of the mechanisms that may lead to variation in DNA repair capacity. Ku, a heterodimeric DNA-binding complex, is directly involved in repair of DNA double-strand breaks. Ku consists of two subunits, Ku70 and Ku80, which are encoded by the XRCC6 and XRCC5 genes, respectively. In the present study, we investigated whether common genetic variant in variable number of tandem repeats (VNTR) XRCC5 and T-991C XRCC6 was associated with an altered risk of breast cancer. The present study included 407 females with breast cancer and 395 age frequency-matched controls which were randomly selected from the healthy female blood donors. The XRCC5 and XRCC6 polymorphisms were determined using PCR-based methods. For XRCC5 polymorphism, in comparison with the 1R/1R genotype, the 0R/0R genotype increased breast cancer risk (OR 9.55, 95%CI 1.19-76.64, P = 0.034). The 1R/3R genotype compared with 1R/1R genotype decreased the risk of breast cancer (Fisher's exact test P = 0.015). There was no association between T-991C polymorphism of XRCC6 and breast cancer risk. Mean of age at diagnosis of breast cancer for 0, 1, 2, 3, and >4 repeat in XRCC5 were 39.2, 41.9, 44.3, 45.8, and 47.3 years, respectively. The Kaplan-Meier survival analysis revealed that the number of repeat was associated with age at diagnosis of breast cancer (log rank statistic = 13.90, df = 4, P = 0.008). The findings of the present study revealed that either breast cancer risk or age at diagnosis of breast cancer was associated with the VNTR polymorphism at promoter region of XRCC5.

Association Between the XRCC6 Polymorphisms and Cancer Risks

“…Additional eligible studies on this topic were identified by a hand search of references of retrieved articles. Studies testing the association between XRCC6 gene polymorphism and cancer were included if all the following conditions were met 5 , 8 – 14 , 16 , 20 – 30 : the publication was a case–control study; the study provided the total number of cases and controls; the study provided available genotype frequency in case and control group, respectively; the study was published in English. The major exclusion criteria were as follows: duplicate data 31 ; abstract, comment, review or editorial.…”

Gene polymorphism in DNA repair genes XRCC1 and XRCC6 and association with colorectal cancer in Swedish patients

“…The subunits Ku70 and Ku80 are encoded by XRCC6 and XRCC5, respectively . The polymorphisms in these genes and the susceptibility to various cancers such as breast , hepatocellular and digestive system cancer have been reported. Human XRCC6 maps to chromosome 22 and specifically the rs2267437 polymorphism (C > G) is located in the promoter of the gene .…”

Roles of Polycomb gene EED in pathogenesis and prognosis of acute myeloid leukemia and diffuse large B cell lymphoma

“…XRCC5 encodes X-ray repair cross complementing 5 and functions as modulating chromosomal stability. It is down-regulated both in non-small cell lung cancer and breast cancer with hyper-methylation in promotor region; the SNPs in XRCC5 promoter region might be susceptible to breast cancer Rajaei et al 2014).…”