CDH1 Gene rs1801552 C/T Polymorphism Increases Susceptibility to Esophageal Squamous Cell Carcinoma but Not to Gastric Cardiac Adenocarcinoma.

PURPOSE: The present study aimed to investigate whether the single nucleotide polymorphism (SNP) rs1801552 C/T in CDH1 gene is correlated with the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), as a preliminary study. METHODS: The rs1801552 C/T polymorphism was genotyped by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 1316 cancer patients (810 ESCC and 506 GCA) and 1966 controls in north China. We performed two case-control studies, each of which included a population-based set and a hospital-based set. RESULTS: The data showed that the rs1801552 C/T polymorphism was associated with the risk of ESCC. Allelotype and genotype distributions of the rs1801552 C/T polymorphism in ESCC patients of high-incidence region and hospital were significantly different from that in their respective controls (p < 0.05). Compared with C/C genotype, T/T genotype increased the risk of ESCC in high-incidence region and hospital (age, sex, smoking status and family history of UGIC adjusted odds ratio (OR) = 1.79 and 2.10, 95% confidence interval (CI) = 1.23-2.60 and 1.10-4.04, respectively). Allelotype and genotype distributions of the rs1801552 C/T polymorphism in GCA patients were not significantly different from that in their controls, respectively (p > 0.05). CONCLUSIONS: The findings in the present pilot study suggest that the rs1801552 C/T polymorphism was associated with the risk of ESCC, but was not associated with the risk of GCA in high-incidence region and hospital.

TIM-3 polymorphism is involved in the progression of esophageal squamous cell carcinoma by regulating gene expression.

The T-cell immunoglobulin and mucin domain containing molecule 3 (TIM-3), a crucial immune regulatory molecule, is an emerging immune checkpoint target for cancer therapy. Our study aimed to investigate the association between TIM-3 polymorphisms (rs10053538 C > A, rs10515746 C > A, and rs1036199 A > C) and the susceptibility and prognosis of esophageal squamous cell carcinoma (ESCC). We further detect the effects of polymorphisms on TIM-3 expression. Two independent case-control sets (population-based and hospital-based sets) were performed in total 994 ESCC patients and 998 controls. TIM-3 polymorphisms were genotyped by polymerase chain reaction-ligase detection reaction (PCR). Survival data were available for 198 patients who received platinum-based chemotherapy after surgery. The regulation on TIM-3 expression by the polymorphisms was investigated in 35 patients using real-time quantitative PCR. The association between mRNA level of TIM-3 and survival was detected by using Kaplan-Meier plotter database. We found that for rs10053538 C > A polymorphisms, A allele was associated with significant increased risk of ESCC (odds ratios [OR] = 1.34, 95%CI = 1.05-1.72), and CA/AA genotypes enhanced susceptibility to ESCC for smokers (adjusted OR = 1.61, 95%CI = 1.00-2.59). The patients with AA genotypes had significantly poor prognosis (adjusted HR = 4.98, 95%CI = 1.14-21.71). The patients carrying CA/AA genotypes had significantly higher mRNA levels of TIM-3 than those carrying the CC genotype. Furthermore, high mRNA level of TIM-3 had a shorter overall survival in patients (HR = 2.56, 95%CI = 1.04-6.28). For rs10515746 C > A and rs1036199 A > C polymorphisms, there were no statistical correlation with the progression of ESCC. These data demonstrate that rs10053538 C > A polymorphisms may be associated with the susceptibility and prognosis of ESCC patients through regulating expression of TIM-3.

PARP1 Gene Polymorphisms and the Prognosis of Esophageal Cancer Patients from Cixian High-Incidence Region in Northern China.

OBJECTIVE: Poly (ADP-ribose) polymerase 1 (PARP1), as a key enzyme in the base excision repair pathway, plays a crucial role in tumorigenesis and progression. This study aimed to assess whether polymorphisms of PARP1 gene could be used as predictive biomarkers for the survival of esophageal squamous cell carcinoma (ESCC) patients from Cixian high-incidence region in northern China. METHODS: In 203 ESCC patients with survival information, PARP1 rs1136410 T/C and rs8679 T/C single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method. All statistical analyses were performed using the SPSS ver. 22.0 software package (SPSS, Chicago, IL, USA). RESULTS: The mean age ± standard deviation of the ESCC patients was 60.4 ± 7.9 years. There was no significant relation of sex, age, smoking status and upper gastrointestinal cancer family history with the survival time of the ESCC patients. The mean survival time of rs1136410 T/T, T/C and C/C genotype carriers were 43.3, 42.3 and 46.6 months, respectively. The rs1136410 was not associated with the survival time of the ESCC patients. For rs8679, the mean survival time of T/T genotype carriers was 43.7 months, which was not significantly different from that of the patients with T/C genotype (42.1 months). CONCLUSION: In Cixian high-incidence region from northern China, rs1136410 and rs8679 SNPs might not be used to predict survival of ESCC patients. There is a need to explore whether other SNPs of PARP1 gene have an effect on prognosis of ESCC patients.

Association of cytotoxic T-lymphocyte associated protein 4 gene polymorphisms with the risk and prognosis of oesophageal cancer in a high-incidence region from northern China.

The most important anti-tumour immune response is mediated by T lymphocytes. Cytotoxic T lymphocyte-associated protein 4 (CTLA4) plays a critical role in the immune surveillance against tumours as an inhibitory immune checkpoint molecule of T-cell activation. This study was designed to explore the association of CTLA4 polymorphisms with the susceptibility to oesophageal squamous cell carcinoma (ESCC) and prognosis of patients with ESCC in a high-incidence population from northern China. CTLA4 rs5742909 C/T and rs231775 G/A single nucleotide polymorphisms (SNPs) were genotyped using polymerase chain reaction-ligase detection reaction (PCR-LDR) method in 577 ESCC patients and 580 controls. Upper gastrointestinal cancer family history increased the risk of ESCC (the sex-, age- and smoking status-adjusted OR = 1.383, 95%CI = 1.094-1.749). The genotype frequencies of these two SNPs in the patients with ESCC were similar to that in the controls. Survival analyses were conducted in 204 patients with ESCC with five-year survival information. The mean survival time of ESCC patients with rs231775 SNP A/A genotype in age over 60 years group was 23.2 months, significantly shorter than that of those with G/G genotype (47.3 months). The A/A genotype was associated with increased death risk of patients with ESCC older than 60 years (adjusted HR = 4.544, 95%CI = 1.913-10.790). CTLA4 rs231775 SNP might be used as genetic marker of worse prognosis for patients with ESCC over 60 years in a high-incidence population from northern China.

The effect of polymorphisms in the promoter of the BIRC5 gene on the risk of oesophageal squamous cell carcinoma and patient's outcomes.

Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is an inhibitor of apoptosis proteins and plays a key role in apoptosis or programmed cell death. In the present study, we evaluated the effect of BIRC5 gene polymorphisms on the risk of developing oesophageal squamous cell carcinoma (ESCC) and patients' outcomes in a high-incidence population from northern China. A population-based case-control study was performed in 597 ESCC patients and 597 control subjects.Survival data were available for 211 patients who received platinum-based chemotherapy after surgery. Five polymorphisms (-31 C>G, -241 C>T, -625 G>C, -644 T>C and -1547 A>G) in the promoter of the BIRC5 gene were genotyped by the polymerase chain reaction-ligase detection reaction (PCR-LDR) method. Compared with the -31 CC genotype, the -31 CG/GG genotype of -31 C>G single nucleotide polymorphism (SNP) was associated with a significant elevated risk of ESCC [adjusted odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.07-1.84]. Interestingly, this association was stronger among females, younger patients and non-smokers in stratified analyses (adjusted OR = 1.72, 95% CI = 1.07-2.75; adjusted OR = 1.61, 95% CI = 1.10-2.36; adjusted OR = 1.80, 95% CI = 1.26-2.58, respectively]. Survival analyses showed that the T allele of -241 C>T SNP was associated with poor prognosis [hazard ratio (HR) = 2.99, 95% CI = 1.09-8.19) and that the C allele of -625 G>C SNP was associated with good prognosis (HR = 0.62, 95% CI = 0.38-0.99) in ESCC patients. The -31 C>G polymorphism may be involved in the development of ESCC, and the -241 C>T and -625 G>C polymorphisms may be useful prognostic markers for ESCC.

Association between the vascular endothelial growth factor gene polymorphisms and the risk of polycystic ovary syndrome in Northern Chinese women.

The present study aimed to investigate whether the single nucleotide polymorphisms (SNPs) rs2010963 and rs833061 in vascular endothelial growth factor (VEGF) gene is correlated with the risk of polycystic ovary syndrome (PCOS) in Northern Chinese women, as a preliminary study. This case-control study comprised 118 women with PCOS and 130 healthy women as controls. Genotyping of the two polymorphisms within the VEGF gene 5'-untranslated region and promoter region were performed using polymerase chain reaction ligase detection reaction method. The data showed that there was a significant difference in the genotype and allele distribution of the rs2010963 polymorphism between the PCOS group and the control group (p = .020 and .033, respectively). The women carrying the C allele (G/C + C/C genotype) had a lower risk of PCOS compared with the women with G/G genotype [odds ratio (OR = 0.55; 95% confidence interval (CI) = 0.33-0.91]. Our study shows for the first time that the rs2010963 polymorphism may be associated with a risk of PCOS in Northern Chinese women.

Phospholipase C ε-1 gene polymorphisms and prognosis of esophageal cancer patients from a high-incidence region in northern China.

Recent genome-wide association studies identified susceptibility loci for esophageal squamous cell carcinoma (ESCC), the most common histological type of esophageal cancer, in the phospholipase C ε-1 gene (PLCE1). The aim of the present study was to investigate whether polymorphisms of PLCE1 were associated with the prognosis of ESCC patients in a high-incidence region of northern China. The PLCE1 rs2274223 A/G and rs11599672T/G single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-ligase detection reaction method in 207 ESCC patients with survival information. The mean age ± standard deviation of the 207 ESCC patients was 60.3±7.9 years. Sex, age, smoking status and family history of upper gastrointestinal cancer were not found to be associated with the survival time of ESCC patients. The mean survival time of rs2274223 SNP A/A, A/G and G/G genotype carriers were 42.9, 43.4 and 46.3 months, respectively; for rs11599672 SNP T/T, T/G and G/G genotype carriers the survival time were 42.8, 43.8 and 42.7 months, respectively. There was no significant difference in survival time among the ESCC patients with different genotypes of rs2274223 and rs11599672 SNPs. In conclusion, PLCE1 rs227423 and rs11599672 SNPs cannot be used as predictive markers for the survival of ESCC patients from a high-incidence region of northern China.

Programmed death-1 ligand-1 gene rs2890658 polymorphism associated with the risk of esophageal squamous cell carcinoma in smokers.

BACKGROUND: The most important anti-tumor immune response is mediated by T lymphocytes. The interaction of programmed death-1 ligand-1 (PD-L1) with its receptor provides an inhibitory signal in T lymphocytes activation and proliferation. OBJECTIVE: This study aimed to investigate whether polymorphisms of PD-L1 were associated with the risk and prognosis of esophageal squamous cell carcinoma (ESCC) in a high-incidence population from Northern China. METHODS: PD-L1 rs2890658 A/C and rs4143815 C/G single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method in 575 ESCC patients and 577 healthy controls. RESULTS: There was no significant difference in the genotype frequencies of these two SNPs between the ESCC patients and the healthy controls. However, for rs2890658 A/C SNP, compared with the C/C genotype, the A/C genotype increased the risk of ESCC for the smokers (OR = 1.513, 95% CI = 1.006-2.287). Among the 575 ESCC patients, the survival information of 202 ESCC patients was collected. Neither the rs2890658 A/C SNP nor the rs4143815 C/G SNP was associated with the survival of ESCC patients. CONCLUSIONS: PD-L1 rs2890658 A/C SNP might be used as risk marker of the susceptibility to ESCC for the Han nationality in a high-incidence population from Northern China.

The effect of polymorphisms in PD-1 gene on the risk of epithelial ovarian cancer and patients' outcomes.

OBJECTIVE: Programmed death-1 (PD-1), an important immunosuppressive molecule, plays a key role in tumor-cell-mediated immune escape. In the present study, we evaluated the effect of PD-1 gene polymorphisms on the risk of developing epithelial ovarian cancer (EOC) and patients' outcomes. METHODS: A case-control study was performed in 620 EOC patients and 620 control women. Survival data were available for 258 patients who received platinum-based chemotherapy after cytoreductive surgery. RESULTS: There were significant differences in the genotype and allele distribution frequencies of the PD-1.1 A/G between cases and controls (P=0.028 and P=0.02, respectively). Compared with the AA genotype, AG and GG genotypes may significantly decrease the risk of developing EOC (OR=0.71, 95%CI=0.54-0.94; OR=0.68, 95%CI=0.50-0.94, respectively). We did not find a significant difference in the genotype distribution frequency of the PD-1.5 C/T between cases and controls (P=0.096), but the frequency of T alleles was significantly lower in the EOC cases than that in the controls (P=0.033). Compared to the carriers with C alleles, the carriers with T alleles were at a significantly decreased risk of developing EOC (OR=0.82, 95%CI=0.69-0.98). Survival analysis showed that the two polymorphisms were not associated with patients' outcomes. CONCLUSIONS: PD-1 gene polymorphisms may be involved in the development of EOC, but not associated with its clinical outcome in EOC patients among northern Chinese women.

Association of programmed death-1 polymorphisms with the risk and prognosis of esophageal squamous cell carcinoma.

Programmed death-1 (PD-1) is an immunoinhibitory receptor belonging to the CD28 family. This study was designed to investigate the association of PD-1 rs36084323:A>G, rs2227981:C>T, rs2227982:C>T and rs10204525:A>G single nucleotide polymorphisms (SNPs) with the risk and prognosis of esophageal squamous cell carcinoma (ESCC) in a high-incidence population from Northern China. These four SNPs were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method in 584 ESCC patients and 585 healthy controls. The rs2227981:C>T SNP C/T genotype increased the risk of ESCC for the smokers (OR = 1.483, 95% CI = 1.018-2.160) and rs2227982:C>T SNP C/T genotype enhanced susceptibility to ESCC for the females (OR = 1.708, 95% CI = 1.056-2.762). For rs10204525:A>G SNP, A/A genotype was related to increased risk of ESCC (OR = 1.735, 95% CI = 1.086-2.771) overall. Among the 584 ESCC patients, the survival information of 204 ESCC patients was collected. The rs36084323:A>G SNP A/G genotype was associated with lower risk of death in ESCC patients with upper gastrointestinal cancer (UGIC) family history (HR = 0.339, 95%CI = 0.115-0.996). The rs2227982:C>T SNP C/T genotype was associated with lower risk of death in smoker ESCC patients and ESCC patients with UGIC family history (HR = 0.409 and 0.292, 95%CI = 0.194-0.863 and 0.101-0.847). PD-1 rs2227981:C>T, rs2227982:C>T and rs10204525:A>G SNPs might be used as predictive markers of the susceptibility to ESCC for the Han nationality in a high-incidence population from Northern China. PD-1 rs36084323:A>G and rs2227982:C>T SNPs were associated with the prognosis of the Han ESCC patients in this high-incidence region.

XPG Gene Polymorphisms and the Risk of Gastric Cardia Adenocarcinoma.

BACKGROUND: Polymorphisms in DNA repair genes can alter an individual's DNA repair capability and contribute to the risk of various cancers. AIMS: This study was designed to evaluate the association of single-nucleotide polymorphisms (SNPs) in the XPG gene with the risk of gastric cardia adenocarcinoma (GCA) in a high-incidence population in northern China. METHODS: Two SNPs from 431 GCA patients and 432 healthy controls were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. RESULTS: The rs751402 C/T SNP T allele and the T/T genotype were associated with an increased risk of GCA in younger individuals (≤61 years) (odds ratio [OR] = 1.33 and 1.77, 95% confidence interval [CI] = 1.00-1.76 and 1.12-3.30, respectively). The rs873601 G/A SNP was not associated with susceptibility to GCA. CONCLUSIONS: Our findings indicate that the rs751402 C/T SNP has potential as a predictive marker for the risk of GCA and that carriers of the T/T genotype should receive periodic upper gastrointestinal fiber tests to facilitate the early detection and early treatment of GCA.

Predicting the outcome of platinum-based chemotherapies in epithelial ovarian cancer using the 8092C/A polymorphism of ERCC1: a meta-analysis.

BACKGROUND: In the present study, we performed this meta-analysis to estimate the association between excision repair cross-complementation group 1 (ERCC1) gene polymorphism and clinical resistance to platinum-based chemotherapy in the patients with epithelial ovarian cancer (EOC). METHODS: A total of 10 studies consist of 1479 EOC patients relating ERCC1 rs11615C/T and rs3212986C/A polymorphisms to the response of platinum-based chemotherapy were included in this meta-analysis. RESULTS: The analysis showed that the AA genotype of the rs3212986C/A polymorphism in ERCC1 was associated with progression-free survival of EOC patients (HR = 1.39, 95% CI = 1.12-1.73) and that the CA or AA genotypes could influence overall survival (HR = 1.28, 95% CI = 1.05-1.56; and HR = 1.55, 95% CI = 1.17∼2.05, respectively). CONCLUSIONS: The ERCC1 rs3212986C/A polymorphism may be a useful prognostic marker in platinum-based treatment of EOC.

Hsa-miR-196a2 functional SNP is associated with the risk of ESCC in individuals under 60 years old.

BACKGROUND AND AIM: The miR-196a2 gene contains a C/T polymorphism (rs11614913). Its presence could change the conformation of secondary structure of miR-196a2 RNA, and directly affect the binding to target mRNAs and the miRNA maturation process. Both of which eventually alter protein expression and contributed to cancer susceptibility. This study assessed whether the rs11614913 single nucleotide polymorphism (SNP) could affect an individual's susceptibility to esophageal squamous cell carcinomas (ESCC). METHODS: SNP rs11614913 was genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) in 597 ESCC patients and 597 control subjects. RESULTS: Overall, there were no significant differences in the frequency of the miRNA-196a2 SNP rs11614913 genotype between the ESCC cases and the controls (χ(2) = 1.395, p = 0.498). The TT genotype, CT genotype and CT/TT combined genotype (dominant model) did not modify the risk of ESCC as compared with the CC genotype. Comparisons of the TT genotype to the CT/CC combined genotype did not reveal a significant association to ESCC, too. However, further analyses revealed an increased risk of ESCC in the dominant model (OR = 1.56, 95% CI = 1.08-2.26) and the allele frequency comparison (OR = 1.31, 95% CI = 1.06-1.63) in the ≤60-year-old group. CONCLUSIONS: These results suggest that the miRNA-196a2 functional polymorphism rs11614913 might be an effective genetic marker for ESCC risk assessment in individuals younger than 60 years of age from a region of high ESCC incidence in northern China.

DNA repair gene associated with clinical outcome of epithelial ovarian cancer treated with platinum-based chemotherapy.

OBJECTIVE: The nucleotide excision repair (NER) and base excision repair (BER) pathways, two DNA repair pathways, are related to platinum resistance in cancer treatment. In this paper, we studied the association between single nucleotide polymorphisms (SNPs) of involved genes and response to platinum-based chemotherapy in epithelial ovarian cancer. METHOD: Eight SNPs in XRCC1 (BER), XPC and XPD (NER) were assessed in 213 patients with epithelial ovarian cancer using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) techniques. RESULTS: The median progression-free survival (PFS) of patients carrying the Lys/Lys and Lys/Gln+Gln/Gln genotype of the XPC Lys/Gln polymorphism were 25 and 12 months, respectively (P=0.039); and the mean overall survival (OS) of patients was 31.1 and 27.8 months, respectively (P=0.048). Cox's multivariate analysis suggested that patients with epithelial ovarian cancer with the Gln allele had an increased risk of death (HR=1.75; 95% CI=1.06-2.91) compared to those with the Lys/Lys genotype. There are no associations between the XPC PAT+/-, XRCC1 Arg194Trp, Arg280His, Arg399Gln, and XPD Asp312Asn, Lys751Gln polymorphisms and the survival of patients with epithelial ovarian cancer when treated with platinum-based chemotherapy. CONCLUSION: Our results indicated that the XPC Lys939Gln polymorphism may correlate with clinical outcome of patients with epithelial ovarian cancer when treated with platinum-based chemotherapy in Northern China.

Genetic polymorphisms in the Fas and FasL genes are associated with epithelial ovarian cancer risk and clinical outcomes.

AIM: In this study, we evaluated whether functional polymorphisms within the Fas and FasL genes were associated with the risk of developing epithelial ovarian cancer (EOC) and survival of patients with EOC. METHODS: A case-control study was performed in 342 EOC patients and 344 control women. The genotypes of three promoter region polymorphisms (Fas -1377G/A, -670A/G and FasL -844T/C) were determined using ligase detection reaction-polymerase chain reaction (LDR-PCR). The clinical outcomes in 202 EOC patients were compared across genotypes. RESULTS: The genotype frequencies of the FasL -844 T/C polymorphism were significantly different between the case and control groups (P=0.034). Compared to the T/T and T/C genotypes, the C/C genotype significantly increased the risk of developing EOC (OR=1.46, 95% CI=1.08-1.99). The survival analysis showed that the Fas -1377G/A and -670A/G polymorphisms were related to prognosis in EOC patients. Compared with patients with the G/G genotype of the -1377G/A polymorphism, patients carrying the A allele had a shorter PFS and OS, as determined by univariate and multivariate analysis (HR=1.81, 95% CI=1.26-2.62 and HR=1.86, 95% CI=1.15-3.00, respectively). Similarly, Kaplan-Meier and Cox proportional hazard model analyses indicated that patients carrying the G allele of Fas -670A/G polymorphisms had shorter PFS and OS than those carrying the AA genotype (HR=1.67, 95% CI=1.15-2.42 and HR=1.80, 95% CI=1.10-2.94, respectively). CONCLUSIONS: Functional polymorphisms in the Fas and FasL genes may be involved in epithelial ovarian cancer development and progression in northern Chinese women.

[Polymorphisms of ERCC1 gene and outcomes in epithelial ovarian cancer patients with platinum-based chemotherapy].

OBJECTIVE: To explore the relationship among single nucleotide polymorphism (SNP) of excision repair cross-complementing 1(ERCC1) gene, chemotherapy sensitivity and clinical outcomes of epithelial ovarian cancer (EOC) patients treated with platinum. METHODS: Six tag single nucleotide polymorphisms (tagSNP;rs11615, rs3212986, rs735482, rs3212955, rs12610134 and rs3212958) were chose from ERCC1 gene. The genotypes of 6 tagSNP were determined by Snapshot method in 220 EOC patients. Primary clinical outcomes parameter contained EOC patients' responses to platinum-based chemotherapy, progression-free survival (PFS) and overall survival (OS) were analysed. RESULTS: The rs11615 C/T SNP of ERCC1, CC, CT and TT genotype frequencies were 53.1%, 45.6%, 1.4% in responders to platinum-based chemotherapy, while 52.0%, 35.6%, 12.3% in non-responders, respectively, in which there was significant difference between the two groups (P = 0.002) . Compared with the patients with CC genotype, the patients carrying TT genotype had a significantly poor response to platinum-based chemotherapy (OR = 6.22, 95%CI:1.12-34.42). Similarly, the genotypes frequencies distribution of rs11615 C/T SNP of ERCC1 was different between the recurrence and non-recurrence group, death and survival group (all P < 0.05). Kaplan-Meier survival analysis showed that the genotypes frequencies distribution of rs11615 C/T SNP of ERCC1 was associated with PFS and OS (P < 0.01) of EOC patients. Cox's multivariate analysis suggested that patients with TT genotype had a shorter PFS (HR = 2.19, 95%CI:1.14-4.22, P = 0.009) and OS (HR = 2.22, 95%CI:1.06-4.64, P = 0.021) compared with those carrying CC genotype [adjusting for age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological type, grade and tumor residual size]. The genotypes frequencies distribution of rs3212986, rs735482, rs3212955, rs12610134 and rs3212958 SNP of ERCC1 did not show the significant difference between the responders to platinum-based chemotherapy and non-responders. The other 5 tagSNP may not be associated with the PFS and OS of EOC patients (all P > 0.05). CONCLUSION: The rs11615 SNP of ERCC1 may become a valuable prognostic biomarker for EOC patients treated with platinum-based chemotherapy.

A functional polymorphism rs11614913 in microRNA-196a2 is associated with an increased risk of colorectal cancer although not with tumor stage and grade.

A C/T polymorphism (rs11614913) was identified in the microRNA (miRNA) 196a2 (miR-196a2) gene and was implicated in the susceptibility to cancer. Numerous studies have investigated its association with the risk of colorectal cancer (CRC). However, the results were inconsistent and inconclusive. The present meta-analysis was conducted based on the results of six published case-control studies comprising 1,754 cases and 2,430 controls (up to November, 2012). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the allelic and genotypic comparisons following the co-dominant, dominant and recessive genetic models. The Chi-square-based Q-test was used to assess heterogeneity. Egger's test and inverted funnel plots were used to investigate publication bias. Subgroup analysis was also performed. The results demonstrated that almost all the genetic models (except the model of CT vs. TT) indicated a significant association between rs11614913 polymorphism and CRC risk. The subgroup analysis in an Asian population also demonstrated similar results. However, there was no significant association of miR-196a2 rs11614913 polymorphism with the clinical characteristics of CRC patients. Our results confirmed the association of the polymorphism rs11614913 with the risk of CRC, but not with tumor stage and grade.

PLC-ε1 gene polymorphisms significantly enhance the risk of esophageal squamous cell carcinoma in individuals with a family history of upper gastrointestinal cancers.

BACKGROUND AND AIMS: Phospholipase C epsilon 1 (PLCε1) may regulate cell growth, differentiation, apoptosis and angiogenesis and play an important role in carcinogenesis and the progression of several cancers. This study was designed to validate the association of the PLCε1 rs2274223 single nucleotide polymorphism (SNP) with esophageal squamous cell carcinoma (ESCC) as identified by genome-wide association studies (GWAS) and further assess whether the rs11599672 SNP could affect an individual's susceptibility to ESCC. METHODS: These two SNPs were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) in 527 ESCC patients and 527 controls. RESULTS: Compared with the rs2274223 SNP AA genotype, other genotypes or combined genotypes all enhanced the risk of ESCC. Further analyses showed that AG/GG genotype carriers with a family history of upper gastrointestinal cancers (UGIC) had an increased risk of ESCC than those AA genotype carriers without UGIC family history (OR = 2.10, 95% CI = 1.46-3.10). Overall, rs11599672 SNP had no influence on ESCC susceptibility. However, UGIC family history elevated the risk of ESCC for subjects with the TT genotype (OR = 1.59, 95% CI = 1.13-2.24). CONCLUSIONS: These results highlighted the role of a genetic factor in ESCC and suggested that the PLCε1 rs2274223 SNP might be an effective genetic marker to assess the risk of ESCC in individuals with a UGIC family history from a region of high incidence in northern China.

nm23 gene polymorphisms are associated with survival of patients with epithelial ovarian cancer but not with susceptibility to disease.

OBJECTIVE: nm23, a tumor metastasis suppressor gene, has been linked to protection against tumorigenesis and tumor metastasis. This study evaluated whether genetic variants in the nm23 gene were associated with susceptibility to epithelial ovarian cancer (EOC) or the clinical outcome of patients. METHODS: A case-control study was performed with 302 patients with epithelial ovarian cancer and 302 control women. According to the genotypes, the outcome in 213 EOC patients was compared. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier plots and Cox models adjusted for clinical factors. RESULTS: The case-control analysis showed that the rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter were not associated with the risk of developing EOC. In contrast, survival analysis showed that the rs2302254 C/T polymorphism was related to the prognosis of EOC patients. Compared with patients carrying the C/C genotype, patients carrying the T/T genotype had a shorter median PFS and median OS by Kaplan-Meier plots and Cox models adjusted for clinical factors. For rs16949649 T/C polymorphisms, Kaplan-Meier analysis indicated that patients carrying the homozygous C/C genotype had shorter PFS and OS than those carrying the T allele (T/T+T/C genotype). The Cox proportional hazard model analysis suggested that this relationship was only retained in OS when adjusted for clinical factors. CONCLUSION: Our studies suggest that rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter may influence the prognosis of patients with epithelial ovarian cancer.

ERCC1 gene +262A/C polymorphism associated with risk of gastric cardiac adenocarcinoma in nonsmokers.

BACKGROUND AND AIMS: Polymorphisms in DNA repair gene may alter an individual's DNA repair capacity and be associated with the risk of various cancers. This study was designed to investigate whether ERCC1 +262A/C and XPF -357A/C polymorphisms affect individual susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). METHODS: In 389 ESCC patients vs. 778 healthy controls and 262 GCA patients vs. 524 healthy controls in a high incidence region of northern China, ERCC1 +262A/C polymorphism and XPF -357A/C polymorphism were genotyped by the method of polymerase chain reaction ligase detection reaction (PCR-LDR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. RESULTS: Family history of upper gastrointestinal cancers (UGIC) may increase the risk of ESCC and GCA. Allelotype and genotype distributions of ERCC1 +262A/C and XPF -357A/C polymorphisms in ESCC and GCA patients were not significantly different from that in their respective controls (p >0.05). Compared with ERCC1 +262C/C genotype, A/A genotype decreased the risk of GCA in nonsmokers (age, gender and family history of UGIC adjusted odds ratio [OR] = 0.30, 95% confidence interval [CI] = 0.13-0.70). Neither the A/C nor the C/C genotype was associated with the overall risk of ESCC and GCA when compared with the XPF -357A/A genotype. CONCLUSIONS: ERCC1 +262A/A genotype may reduce the risk of GCA for nonsmokers. XPF -357A/C polymorphism was not associated with the risk of ESCC and GCA in a population of a high-incidence region in northern China.