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.

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.

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.

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.

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.

Association between genetic variants of the VEGFR-2 gene and the risk of developing endometriosis in Northern Chinese Women.

AIM: To investigate the association of tag single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor receptor 2 (VEGFR-2) gene with susceptibility to endometriosis. METHODS: This study comprised 571 patients with endometriosis and 580 women in the control group. Five tag SNPs in the VEGFR-2 gene were selected using a Haploview program, and those SNPs were genotyped by a method of polymerase chain reaction and ligase detection reaction. RESULTS: Statistical results show that there was a significant difference in the genotype and allele distribution of the 1192C/T polymorphism between the disease group and the control group (p = 0.041 and 0.017). The women carrying the T allele (C/T+T/T genotype) had a lower risk of developing endometriosis compared with the women with the C/C genotype (OR 0.75, 95% CI 0.57-0.99). There was no significant difference in the allele and genotype distribution of four other tag SNPs (1719T/A, +31C/T, IVS25-92A/G and IVS6+​54C/T) between the disease group and the control group (all p > 0.05). CONCLUSIONS: Our results suggested that the 1192C/T polymorphisms on the VEGFR-2 gene might affect the risk of developing endometriosis in Northern Chinese women of Han ethnicity.

[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.

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.

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.

Association between genetic polymorphisms in fibroblast growth factor (FGF)1 and FGF2 and risk of endometriosis and adenomyosis in Chinese women.

BACKGROUND: Angiogenesis appears to be an important event in the pathophysiology of endometriosis (EM) and adenomyosis. Two angiogenic factors, fibroblast growth factor (FGF) 1 and 2, play a central role in the initiation of angiogenesis. We investigated whether FGF1 -1385A/G and FGF2 754C/G polymorphisms are associated with a risk of developing EM and adenomyosis. METHODS: Genotypes were analyzed by the PCR-restriction fragment length polymorphism method in two groups of women, of Han ethnicity in north China, aged 16-55 years: (1) 421 EM patients and 421 controls; (2) 269 adenomyosis patients and 269 controls. RESULTS: There was no difference in genotype distribution of the FGF1 -1385A/G polymorphism between adenomyosis cases and controls (P > 0.05), but the frequency of the A allele in EM patients was lower than that in controls (P = 0.013). Genotype and allele frequencies of the FGF2 754C/C polymorphism were significantly different in both EM and adenomyosis cases versus control groups. Compared with C/C homozygotes, the G allele (C/G + G/G) was associated with a decreased susceptibility to developing EM [odds ratio (OR) = 0.575, 95% confidence interval (CI) = 0.387-0.854] and adenomyosis (OR = 0.577, 95% CI = 0.367-0.906). Combined genotype analysis of both polymorphisms also showed differences between cases versus controls (all P < 0.001). CONCLUSIONS: Our study shows for the first time that the FGF2 754C/G polymorphism may be associated with a risk of developing EM and adenomyosis in north Chinese women. Carriers of the G allele in the FGF2 gene appear to be protected from these gynecological diseases. Further studies in other populations, and of other candidate genes, are now warranted.

Association of functional polymorphisms in MMPs genes with gastric cardia adenocarcinoma and esophageal squamous cell carcinoma in high incidence region of North China.

The aim of the present study was to investigate the association of single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMPs) with the risk of gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC). Genotypes were analyzed by polymerase chain reaction-restriction fragment-length polymorphism method in 592 patients and 624 healthy individuals. Significant differences in allele and genotype distributions of MMP-2 -1306C --> T SNP were observed between ESCC and controls (P = 0.02 and 0.01, respectively). Compared with the C/T + T/T genotypes, C/C genotype significantly increased the risk of ESCC (OR = 1.57, 95% CI = 1.10-2.23), especially in individuals in smoker group and in the group with positive family history. The stratification analysis showed there were risk changes of GCA for -735C/C genotype carrier in nonsmoker, for MMP-12 -82G allele and MMP-13 -77A/G genotype carrier in smoker. Our study indicated that these four functional polymorphisms might play roles in developing ESCC and GCA in high incidence region of North China.

Polymorphisms in promoter region of FAS and FASL gene and risk of cardia gastric adenocarcinoma.

BACKGROUND AND AIM: The FAS and FASL system play an important role in regulating apoptotic cell death. This study was designed to investigate the correlation of FAS-1377 G/A, -670 A/G and FASL-844 T/C polymorphisms with susceptibility to gastric cardiac adenocarcinoma in a population of a high-incidence region of Hebei Province. METHODS: FAS-1377 G/A, -670 A/G and FASL-844 T/C polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 262 gastric cardiac carcinoma (GCA) patients and 524 healthy controls. RESULTS: Family history of upper gastrointestinal cancer (UGIC) might increase the risk of developing GCA (age- and sex-adjusted odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.02-1.86). The overall allelotype and genotype distributions of FAS-1377 G/A, and FASL-844 T/C polymorphisms in GCA patients did not significantly differ from that in healthy controls (P > 0.05). Compared with individuals with a FAS-670 A/A genotype, individuals with an A/G genotype in a smoker group had a lower risk of developing GCA (age, sex, and family history of UGIC adjusted OR = 0.55, 95% CI = 0.34-0.88). When the genotypes of FAS and FASL single nucleotide polymorphisms (SNP) were combined to analyze, no significant correlation was found between these SNP and the risk for GCA development. CONCLUSION: In the high-incidence region of Hebei Province, FAS-1377 G/A and FASL-844 T/C polymorphisms were not associated with the risk of GCA. However, the FAS-670 A/G genotype might decrease the risk of GCA for smoker individuals.

Association of vascular endothelial growth factor gene polymorphisms with susceptibility to epithelial ovarian cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a major angiogenic factor involved in a number of pathological processes, including neovascularization, a crucial step in the development of solid malignancies. The aim of this study was to investigate the association of polymorphisms in the VEGF gene with susceptibility to epithelial ovarian cancer (EOC). METHODS: This case-control study included 303 EOC patients and 303 healthy controls. Genotyping of the VEGF gene polymorphisms at j460C/T, j1154G/A, j2578C/A, and +936C/T were performed by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: No significant difference was found in allele and genotype distributions of the -460C/T, +936C/T, and -2578C/A polymorphisms between patients and controls. However, the frequencies of -1154G/A genotype and allele were significantly different between the two groups (P = 0.037, P = 0.013). Compared with the G/A + A/A genotype, the G/G genotype could significantly increase the risk of developing EOC (odds ratio, 1.64; 95% confidence interval, 1.12Y2.39). The haplotype analysis suggested that the -460T/ -1154A/ -2578C haplotype exhibited a decrease in the risk of developing EOC compared with the -460T/ -1154G/ -2578C haplotype (odds ratio, 0.644; 95% confidence interval, 0.415-0.999). CONCLUSIONS: The study suggested a possible association between the VEGF -1154G/A polymorphism with susceptibility to EOC, but there is no support for an association of the VEGF -460C/T, +936C/T, and -2578C/A polymorphisms with the risk for EOC.

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 polymorphisms -1154G/A and -2578C/A in the vascular endothelial growth factor gene with decreased risk of endometriosis in Chinese women.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in the development of endometriosis. The aim of this study was to investigate the association of polymorphisms in the VEGF gene with the susceptibility to endometriosis. METHODS: This study comprised 344 North Chinese women with endometriosis and 360 healthy women without endometriosis recruited as control. Genotyping of the VEGF gene polymorphisms at -460C/T, -1154G/A, -2578C/A and +936C/T were performed by PCR and restriction fragment length polymorphism analysis. RESULTS: No significant difference was found in allele and genotype distributions of the -460C/T, +936C/T polymorphisms between patients and controls. However, the frequencies of -1154G/A, -2578C/A genotype and allele were significantly different between the two groups (all P-value <0.013). The -2578A/A, -1154A/A genotypes were found less frequently in patients with endometriosis compared with controls. The haplotype distributions derived from three polymorphisms (-2578C/A, -1154G/A, -460C/T) differed between the two groups (P = 0.000). CONCLUSIONS: The VEGF-460/-1154/-2578 TGC, CAA, TAA and TAC haplotypes were associated with endometriosis. The -1154A and -2578A alleles may be protective against the development of endometriosis in North Chinese women.

An investigation on the polymorphisms of two DNA repair genes and susceptibility to ESCC and GCA of high-incidence region in northern China.

AIM: To investigate the possible association of three SNPs, XRCC2 C41657T, XRCC2 G4234C and XRCC3 A17893G with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in a population of northern China. METHODS: XRCC2 C41657T, XRCC2 G4234C and XRCC3 A17893G SNP were genotyped by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 583 cancer patients (329 ESCC and 254 GCA) and 614 healthy controls. RESULTS: The genotype distribution of the XRCC2 C41657T in ESCC and GCA patients were significantly different from that in healthy controls (P values = 0.04 and 0.04 respectively). And a significant difference was found in the allele distribution of GCA patients from that in controls (P = 0.01). The XRCC2 C41657T polymorphism was associated with a modest enhancement in ESCC risk and GCA risk: OR for C/T genotype was 1.38 (1.01-1.89) in GCA risk and for T/T genotype was 2.24 (1.10-4.57) in ESCC risk. When stratified for age, smoking status and family history of UGIC, the C/T genotype showed a modest significant trend on the risk of GCA patients in the groups of age < or =50 years and non-smokers, the adjusted OR were 2.84 (1.21-6.66) and 1.62 (1.06-2.49). The T/T genotype significantly increased the susceptibility of GCA patients in negative family history of UGIC (3.04, 1.02-8.32) and to ESCC patients in the group of age >50 years (3.03, 1.31-6.98), Negative family of UGIC (3.03, 1.12-7.07) and smokers (2.64, 1.02-6.83). The genotype and allele distribution of XRCC2 G4234C and XRCC3 A17893G in ESCC and GCA patients were not significantly different from that in healthy controls (all P values were above 0.05). CONCLUSION: In this study, we found that the C41657T polymorphism of XRCC2 genes might modify the risk of ESCC and GCA development.

The functional polymorphisms on promoter region of matrix metalloproteinase-12, -13 genes may alter the risk of epithelial ovarian carcinoma in Chinese.

BACKGROUNDS AND AIMS: Growing evidences indicate that single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) gene promoter may alter MMPs protein expression levels to influence malignant tumors developing and progressing. Our study was to assess the effects of the SNPs in the promoter region of MMP-12 and MMP-13 on the risk of epithelial ovarian carcinoma (EOC) developing and progressing. METHODS: MMP-12 A-82G and MMP-13 A-77G SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism in 256 EOC patients and 329 controls. RESULTS: The A/G genotype frequency of MMP-12 was significantly higher in patients than in controls (7.0% vs 3.3%, P = 0.04); similarly, the frequency of MMP-12 82G allele was higher in patients too (P = 0.04). Compared with A/A genotype, A/G genotype significantly increased the risk of EOC (odds ratio, 2.19; 95% confidence interval, 1.01-4.72). Age-stratified analysis showed that individuals with A/G genotype had a higher risk in the final diagnosis aged younger than 50 years. We observed no overall association between MMP-13-77A/G polymorphism and EOC. However, an elevated positive association was observed for A/A versus G/G + A/G genotypes in mucinous ovarian cancer. Combining the analyzed 2 SNPs, the haplotype distributions in patients were not significantly different from that in controls. CONCLUSION: These results suggested that the G allele of the MMP-12 82A/G polymorphism might be a risk factor for the development and progression of EOC and that the A/A genotype of MMP-13-77A/G polymorphism was associated with special pathological subtype and clinical stage in EOC at least in Chinese women.