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.
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.
In addition, reducing the levels of miR-17-5p/miR-106b-5p, we increased the chemo-sensitivity of RCC/CRC-derived cells to anti-tumour drugs used in the clinic.
Our findings suggest that inheritance of variant alleles in XRCC1Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.
Related databases of Medline, CNKI, and Wanfang were systematic searched for the studies related to XRCC1rs1799782 C>T polymorphisms and colorectal cancer risk in Chinese Han population.
However, we showed that the carriers of allele A in XRCC1 (rs25487, G > A) were connected with a higher risk of disseminated CRC (Odds Ratio = 1.64; 95% Confidence Interval = 1.12-2.41, p = 0.012).
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).
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.
Our results suggest an increased risk for CRC in individuals with XRCC1Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.
After excluding two studies that deviated from the Hardy-Weinberg equilibrium, there remained no significant association between XRCC1R399Q and CRC risk.
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).
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.
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.
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.
The statistically significant association between the XRCC1Arg399Gln polymorphism and CRC risk was observed among studies with high quality and in Asians, but not in Caucasians.