Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70-7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer.

The association between the hOGG1 Ser326Cys polymorphism and gynecologic cancer susceptibility is inconclusive. We performed a comprehensive meta-analysis to precisely estimate of the impact of the hOGG1 Ser326Cys polymorphism on gynecologic cancer susceptibility. Electronic databases including PubMed, Embase, WanFang, and the China National Knowledge Infrastructure were searched for relevant studies. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were determined to assess the strength of the association. Fourteen studies with 2712 cases and 3638 controls were included in the final meta-analysis. The pooled analysis yielded a significant association between the hOGG1 Ser326Cys polymorphism and overall gynecologic cancer susceptibility (dominant model: OR = 1.16, 95% CI = 1.03-1.30, P=0.017). A significantly higher gynecologic cancer risk was found for the European population (homozygous model: OR = 2.17, 95% CI = 1.80-2.61, P<0.001; recessive model: OR = 2.11, 95% CI = 1.41-3.17, P<0.001; dominant model: OR = 1.29, 95% CI = 1.12-1.48, P<0.001; and allele model: OR = 1.40, 95% CI = 1.13-1.74, P=0.002), but not in the Asian population. The stratified analysis by cancer type revealed endometrial cancer was significantly associated with the hOGG1 Ser326Cys polymorphism (dominant model: OR = 1.29, 95% CI = 1.09-1.54, P=0.003; and allele model: OR = 1.28, 95% CI = 1.02-1.60, P=0.031). In conclusion, the hOGG1 Ser326Cys polymorphism was associated with higher overall gynecologic cancer susceptibility, especially for endometrial cancer in the European population.

Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) has been reported to have a relationship with the risk of the development of various cancers. Many studies have described the influence of Ser326Cys polymorphism of the hOGG1 gene on cancer susceptibility. However, the results have remained inconclusive and controversial. Therefore, we performed a meta-analysis to more precisely determine the relationship between the hOGG1 polymorphism and the development of cancer.Electronic databases including PubMed, Embase, Google Scholar, and the Korean Studies Information Service System (KISS) were searched. The odds ratio (OR), 95% confidence interval (CI), and p value were calculated to assess the strength of the association with the risk of cancer using Comprehensive Meta-analysis software (Corporation, NJ, USA). The 127 studies including 38,757 cancer patients and 50,177 control subjects were analyzed for the meta-analysis.Our meta-analysis revealed that G allele of Ser326Cys polymorphism of the hOGG1 gene statistically increased the susceptibility of cancer (all population, OR = 1.092, 95% CI = 1.051-1.134, p < 0.001; in Asian, OR = 1.095, 95% CI = 1.048-1.145, p < 0.001; in Caucasian, OR = 1.097, 95% CI = 1.033-1.179, p = 0.002). Also, other genotype models showed significant association with cancer (p < 0.05, respectively).The present meta-analysis concluded that the G allele was associated with an increased risk of cancer. It suggested that the hOGG1 polymorphism may be a candidate marker of cancer.

BACKGROUND: Since, the relationship between hOGG1 Ser326Cys polymorphism and HCC was inconsistent in the recent literatures. The present meta-analysis based on previous studies was to obtain precise estimation on the issue.
METHODS: A computer search was carried out from PubMed, CBM and EMBASE databases. A total of nine case-control publications with 2583 HCC patients and 2271 controls were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the relationship of Ser326Cys polymorphism and HCC susceptibility. Z test was used to assess the significance of pooled OR. The fixed-effect model or random-effect model was employed according to heterogeneity.
RESULTS: Overall, hOGG1 Ser326Cys polymorphism was in relation with increased risk for HCC under the following genetic models: GG versus CC: OR=2.51, 95% CI=1.67-3.78; GG versus CG + CC: OR=2.27, 95% CI=1.57-3.30; GG + CG versus CC: OR=1.13, 95% CI=1.03-1.24. The subgroup analysis by ethnicity suggested that high risk for HCC was observed in Asians with GG and GG + CG genotype (GG versus CC: OR=2.17, 95% CI=1.49-3.17; GG versus CG + CC: OR=1.96, 95% CI=1.41-2.73; GG + CG versus CC: OR=1.13, 95% CI=1.03-1.25). For subgroup analysis based on source of control, GG genotype of Ser326Cys was significantly associated with HCC risk in hospital-based (HB) controls (GG versus CC: OR=2.31, 95% CI=1.50-3.56; GG versus CG + CC: OR=2.17, 95% CI=1.44-3.28), as well as in population-based (PB) models (GG vs. CC: OR=2.80, 95% CI=1.16-6.77; GG versus CG + CC: OR=2.39, 95% CI=1.08-5.30).
CONCLUSIONS: According to the results, hOGG1 Ser326Cys polymorphism was associated with increased risk of HCC.