Impact of GTF2H1 and RAD54L2 polymorphisms on the risk of lung cancer in the Chinese Han population.

BACKGROUND: Repair pathway genes play an important role in the development of lung cancer. The study aimed to assess the correlation between single nucleotide polymorphisms (SNPs) in DNA repair gene (GTF2H1 and RAD54L2) and the risk of lung cancer. METHODS: Five SNPs in GTF2H1 and four SNPs in RAD54L2 in 506 patients with lung cancer and 510 age-and gender-matched healthy controls were genotyped via the Agena MassARRAY platform. The influence of GTF2H1 and RAD54L2 polymorphisms on lung cancer susceptibility was assessed using logistic regression analysis by calculating odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: RAD54L2 rs9864693 GC genotype increased the risk of lung cancer (OR = 1.33, 95%CI: 1.01-1.77, p = 0.045). Stratified analysis found that associations of RAD54L2 rs11720298, RAD54L2 rs4687592, RAD54L2 rs9864693 and GTF2H1 rs4150667 with lung cancer risk were found in subjects aged ≤ 59 years. Precisely, a protective effect of RAD54L2 rs11720298 on the occurrence of lung cancer was observed in non-smokers and drinkers. GTF2H1 rs4150667 was associated with a decreased risk of lung cancer in subjects with BMI ≤ 24 kg/m2. RAD54L2 rs4687592 was associated with an increased risk of lung cancer in drinkers. In addition, GTF2H1 rs3802967 was associated with a reduced risk of lung squamous cell carcinoma. CONCLUSION: Our study first revealed that RAD54L2 rs9864693 was associated with an increased risk of lung cancer in the Chinese Han population. This study may increase the understanding of the effect of RAD54L2 and GTF2H1 polymorphisms on lung cancer occurrence.

Role of ERCC5 polymorphisms in non­small cell lung cancer risk and responsiveness/toxicity to cisplatin­based chemotherapy in the Chinese population.

Non­small cell lung cancer (NSCLC) is the leading cause of cancer­related deaths worldwide. Cisplatin­based chemotherapy currently represents the main treatment option for patients with NSCLC. The aim of the present study was to evaluate effect of single nucleotide polymorphisms (SNPs) within the excision repair cross­complementing group 5 (ERCC5) gene on susceptibility to NSCLC, as well as the responsiveness to and toxicity of cisplatin chemotherapy. A total of 506 patients with NSCLC and 510 healthy controls were recruited for the present study. All DNA samples were genotyped by the Agena MassARRAY platform. Logistic regression analysis was carried out to assess the relationship between ERCC5 polymorphisms with NSCLC susceptibility and responsiveness to chemotherapy. The rs4771436 TG­GG genotype was associated with increased NSCLC risk. When the data were stratified according to age, sex, tobacco smoking, body mass index and histological type, ERCC5 polymorphisms (rs2016073, rs4771436, rs11069498 and rs4150330) were associated with NSCLC risk. Furthermore, the A allele and GA­AA genotype of rs11069498 were related to the response to chemotherapy. ERCC5 (rs11069498 and rs4150330) polymorphisms were associated with the increased risk of toxicity. However, rs4771436 in ERCC5 gene was significantly correlated with the reduced risk of toxicity. These results suggested a potential relationship between ERCC5 polymorphisms, the risk of NSCLC and the sensitivity to cisplatin­based chemotherapy among Chinese populations.

RAD52 variants influence NSCLC risk in the Chinese population in a high altitude area.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 80% of diagnosed lung cancer patients. RAD52 has been reported to be associated with the development of squamous cell lung carcinoma. In this study, we assessed the relationships of RAD52 genetic polymorphisms and NSCLC risk among the Chinese population at high altitude. METHODS: Eight single nucleotide polymorphisms (SNPs) of RAD52 were genotyped in the Agena MassARRAY platform among 506 NSCLC patients and 510 healthy controls. We examined the association of RAD52 polymorphisms with NSCLC risk using odds ratios (ORs) and 95% confidence intervals (CIs) via multiple genetic models. RESULTS: The rs10774474 A allele was related to a decreased risk of NSCLC in a high altitude population of China (OR = 0.82, 95% CI = 0.69-0.98, p = 0.032), whereas mutant alleles of rs1051672, rs7310449, rs1051669, rs6413436, rs4766377 and rs10849605 significantly increased NSCLC risk. Haplotype analysis showed that four haplotypes of RAD52 polymorphisms conferred an enhanced susceptibility to NSCLC (Ars1051672Grs7310449Trs1051669Ars6413436: OR = 1.29, p = 0.021; Grs1051672Ars7310449Crs1051669Grs6413436: OR = 1.21, p = 0.027; Grs4766377Crs12822733Trs10774474Crs10849605: OR = 1.26, p = 0.032; Ars4766377Crs12822733Ars10774474Trs10849605: OR = 1.21, p = 0.032). CONCLUSIONS: Our findings suggested the remarkable association of RAD52 polymorphisms with NSCLC risk among the Chinese population in a high altitude area. The reviews of this paper are available via the supplemental material section.

The effect of interleukin 10 polymorphisms on breast cancer susceptibility in Han women in Shaanxi Province.

BACKGROUND: Previous studies have reported on several genetic variants related to breast cancer, but a substantial proportion of mutation loci have not yet been identified. In the current study, we aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of interleukin-10 (IL-10) and susceptibility to breast cancer in Shaanxi Han women in China. METHODS: Six SNPs were genotyped in 530 breast cancer patients and 628 healthy women from the First Affiliated Hospital of Xi'an Jiaotong University Hospital. Odds ratios and 95% confidence intervals were calculated by unconditional logistic regression analysis to assess the association between breast cancer risk and polymorphisms of six loci. RESULTS: Two SNPs, rs3024490 and rs1800871, were found to be significantly different between breast cancer patients and healthy women. These SNPs also increased the risk of breast cancer in co-dominant and dominant models. Moreover, another SNP, rs1554286, was significantly associated with an increased risk of breast cancer in the co-dominant model. Functional assessments indicated that these three variants may influence the expression and transcription factor binding of IL-10. CONCLUSIONS: Our findings suggest that variants of IL-10 may be likelihood risk factors for the development and progression of breast cancer. Future studies should replicate this study and evaluate functional assessments in Chinese Han women and women from other regions.

Rs1884444 variant in IL23R gene is associated with a decreased risk in esophageal cancer in Chinese population.

Single nucleotide polymorphisms (SNPs) in interleukin-23 receptor (IL23R) are involved in the pathogenesis of many cancers and autoimmune diseases. IL23R gene is still controversial in the study of esophageal cancer. The aim of this research is to investigate the influence of IL23R SNPs on the risk of esophageal cancer. Five hundred six esophageal cancer and 507 controls frequency matched by age and gender were conducted, and the genotypes were determined by the Agena MassARRAY. Logistic regression analysis was used to evaluate the odd ratios (ORs) and 95% confidence intervals (CIs) of rs1884444 and rs6682925 with susceptibility of esophageal cancer. A total of 30 articles are eligible. Pooled ORs and the 95% CI were calculated using the random-effect model. Database predicts the expression of IL23R gene in esophageal cancer. IL23R rs1884444 allele G decreased the risk of esophageal cancer under allele, genotype, and additive models (allele model: OR = 0.82, 95% CI: 0.68-0.98, P = .032; genotype model: OR = 0.65, 95% CI: 0.44-0.97, P = .035; additive model: OR = 0.82, 95% CI: 0.68-0.98, P = .031). Meta-analysis shown that IL23R rs1884444 increased the risk of overall disease in allele model (OR = 1.16, 95% CI: 1.08-1.25, P < .001), and also increased the risk of gastrointestinal tumor (OR = 1.18, 95% CI: 1.05-1.31, P = .005). The database analysis showed that the expression of IL23R gene was upregulated in esophageal cancer tissues. IL23R rs1884444 may play an important role in the susceptibility of esophageal cancer.