In the univariate analysis, factors found to be significantly associated with an increased risk for CRC were the presence of the XRCC1 AA homozygote (OR= 4.95; 95% CI: 1.99-12.3), a first degree family history of cancer (OR= 1.74; 95% CI: 1.18-2.58), and a high frequency of pork consumption (OR= 1.49; 95% CI: 1.00-2.21).
While, single nucleotide polymorphisms (SNP) of ERCC1 and XRCC1 have be proved to influence clinical outcome of colorectal cancer patients treated with oxaliplatin-based chemotherapy.
PARP1 762 recessive model (OR = 1.57, 95 % CI 1.12-2.20) and XRCC1 194 dominant model (OR = 1.45, 95 % CI 1.12-1.88) were associated with increased CRC risk.
Moreover, the decrease efficiency of DNA repair were correlated with the 399Gln/Gln XRCC1 and the 324His/His MUTYH genotypes occurrence in CRC patients.
Therefore, we examined the associations of XRCC1Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk.
Using a family-based study, we investigated the role of polymorphisms in 4 BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; and XRCC1Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between diets high in red meat or poultry and CRC risk.
Our meta-analysis provides an evidence for the association between XRCC1Arg399Gln polymorphism and colorectal cancer risk in Chinese population, and XRCC1Arg399Gln variant genotypes contribute to increased risk of colorectal cancer in Chinese.
When combined effects of XRCC1 polymorphisms and alcohol consumption were analyzed, we found that the 194Trp or 399Gln alleles further increased the colorectal cancer risk due to high alcohol intake.
Thus, this study was aimed to examine whether XRCC1 plays a role in the 5-FU/AMPK agonist (AICAR)-induced cytotoxic effect on CRC and the underlying mechanisms.
The risk for colorectal cancer did not appear to differ significantly amongst individuals featuring the XRCC1 399Arg/Arg genotype (OR = 1.18; 95% CI, 0.96-1.45), the XRCC3 241Thr/Thr genotype (OR = 1.25; 95% CI, 0.88-1.79) or the XPD 751Gln allele (OR = 1.20; 95% CI, 0.90-1.61), although individuals featuring a greater number of risk genotypes (genotype with OR greater than 1) did experience a higher risk for colorectal cancer when compared to those who didn't feature any risk genotypes (Trend test P = 0.03).
Taking smoking and drinking habits into consideration, we found that subjects with heavy smoking history and XRCC1 194Arg allele had the significantly increased risk for CRC (OR=2.91, 95% CI 1.35-6.24).
We conducted a hospital-based case-control study including 727 cases and 736 healthy controls to evaluate the associations of the polymorphic phase-I and -II biotransformations (CYP1A1, CYP1A2, GSTM1, GSTT1, GSTP1, NAT1 and NAT2) and DNA-repair enzymes (XRCC1, XRCC3 and XPD) with the risk of contracting colorectal cancer.
Results showed that Trp/Trp genotype of XRCC1Arg194Trp and AA genotype of ERCC1 rs2336219 have a significantly increased risk of CRC; Trp allele of XRCC1Arg194Trp and CC genotype of ERCC1 rs735482 were associated with lower response to oxaliplatin-based chemotherapy, a shorter survival and a higher risk of relapse or metastasis.
This meta-analysis confirms the association between XRCC1Arg399Gln polymorphism and CRC risk and suggests that the heterogeneity is not strongly modified by ethnicity and deviation from the Hardy-Weinberg equilibrium.
Weak association was found between the XRCC1 Arg/Arg and Gln/Gln variants and the risk of colorectal cancer (OR = 1.28; 95% CI 1.00-1.84 and OR = 1.13; 95% CI 0.85-2.34, respectively).