XRCC1 Arg399Gln, Arg194Trp and Arg280His polymorphisms in breast cancer risk: a meta-analysis

Abstract

X-ray repair cross-complementing group 1 (XRCC1) plays an important role in base excision and single-strand break repair, as a scaffold protein that brings together proteins of the DNA repair complex, and appears to be a candidate for cancer risk. However, studies on the association between polymorphisms in this protein and cancer have yielded conflicting results. We performed a meta-analysis to investigate the association between the breast cancer and the XRCC1 polymorphisms Arg194Trp (9411 cases and 9783 controls), Arg399Gln (22 481 cases and 23 905 controls) and Arg280His (6062 cases and 5864 controls) in different inheritance models. Our analysis suggested that Arg399Gln was associated with a trend of increased breast cancer risk when using both dominant [odds ratio (OR) = 1.06, 95% confidence interval (CI): 1.00-1.13] and recessive models (OR = 1.12, 95% CI: 1.02-1.23) to analyse the data. In ethnic subgroups and using recessive model analysis: Arg399Gln increased breast cancer risk in Asians (OR = 1.26, 95% CI: 0.96-1.64) and Africans (OR = 1.80, 95% CI: 0.97-3.32), and also while only slightly increasing the breast cancer risk in Caucasians (OR = 1.08, 95% CI: 0.95-1.22). However, Arg194Trp (recessive model, OR = 0.95, 95% CI: 0.75-1.20) and Arg280His (recessive model, OR = 1.28, 95% CI: 0.64-2.55) did not appear to be risk factors for breast cancer. Larger scale primary studies are required to further evaluate the interaction of XRCC1 polymorphisms and breast cancer risk in specific populations.

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: A case–control study

“…The XRCC1 -399Q variant has been associated with lung cancer [41], breast cancer [42,43], colorectal cancer [44], prostate cancer [45], but not with bladder cancer [49].…”

“…Both XRCC1 R399Q and ERCC1 N118N have been found associated with cancer in different studies [41][42][43][44][45][46][47]. The combination of ERCC1 and XRCC1 polymorphisms better predicts clinical outcome to oxaliplatin-based chemotherapy in metastatic colorectal cancer [48].…”

XRCC1 Arg399Gln and Arg194Trp polymorphisms in prostate cancer risk: a meta-analysis

“…[32][33][34] XRCC1, which is involved in the DNA repair, has been studied extensively about the relationship with different cancers, such as urothelial bladder cancer, 35 breast cancer, 36 PCa 25,37 and so on. Previous results of the studies on the relationship between XRCC1 polymorphisms and PCa risk were contradictory.…”

X-Ray Repair Cross-Complementing Group 1(XRCC1) Genetic Polymorphisms and Thyroid Carcinoma Risk: a Meta-Analysis

“…There have been more than 300 validated SNPs (single nucleotide polymorphism) in the XRCC1 gene, however, only three SNPs have been extensively studied including Arg194Trp, Arg280His and Arg399Gln. The three SNPs have been reported to be associated with many types of cancer, such as lung cancer (Dai et al, 2012), gastric cancer (Chen et al, 2012), breast cancer (Huang et al, 2009) and leukemia .…”