Association between F508 deletion in CFTR and chronic pancreatitis risk.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) has been reported to influence individual susceptibility to chronic pancreatitis (CP), but the results of previous studies are controversial. AIMS: We performed a study to demonstrate the relationship between CFTR and CP. METHODS: We searched PubMed, Scopus, and Embase for studies of patients with CP. Seven studies from 1995 to 2016 were identified, and included 64,832 patients. Pooled prevalence and 95% confidence intervals (CIs) were calculated. RESULTS: F508 deletion in CFTR was significantly positively associated with CP risk in the overall analysis (odds ratio [OR]=3.20, 95% CI: 2.30-4.44, I2=31.7%). In subgroup analysis stratified by ethnicity, F508 deletion was significantly associated with CP risk in Indian populations, using a fixed effects model (ORs=5.45, 95% CI: 2.52-11.79, I2=0.0%), and in non-Indian populations, using a random effects model (ORs=3.59, 95% CI: 1.73-7.48, I2=60.9%). At the same time, we found that Indians with F508 deletion had much higher CP prevalence than non-Indians. Interestingly, F508 deletion was also associated with CP and idiopathic CP risk in subgroup analysis stratified by aeitiology, using the fixed effects model. CONCLUSIONS: Based on current evidence, F508 deletion is a risk factor for CP, and Indians with F508 deletion have much higher CP morbidity.

Association Between the Asp312Asn, Lys751Gln, and Arg156Arg Polymorphisms in XPD and the Risk of Prostate Cancer.

Prostate cancer is the most common solid cancer and genetic factors play important roles in its pathogenesis. XPD is one of the 8 core genes involved in the nucleotide excision repair pathway. The relationship between Asp312Asn, Lys751Gln, and Arg156Arg polymorphisms in XPD and prostate cancer risk is a controversial topic. Therefore, we conducted a meta-analysis to explore the relationship between these 3 polymorphisms and the risk of developing prostate cancer. We searched the electronic literature in PubMed and Google Scholar for all relevant studies (last updated January 1, 2017). The pooled odds ratios and 95% confidence intervals for the associations between the Asp312Asn, Lys751Gln, or Arg156Arg polymorphisms in XPD and prostate cancer risk were calculated. To evaluate the effects of specific study characteristics on the association of these 3 polymorphisms and prostate cancer risk, we performed subgroup analysis if 2 or more studies were available. After an extensive literature review, 7 publications regarding Asp312Asn genotype distribution with 8 case-controls, 9 publications regarding Lys751Gln genotype distribution with 10 case-controls, and 3 publications regarding Arg156Arg genotype distribution with 4 case-controls were selected. The results showed that Asp312Asn (odds ratio = 1.34, 95% confidence interval: 0.96-1.87, P = .000), Lys751Gln (odds ratio = 0.98, 95% confidence interval: 0.89-1.08, P = .986), and Arg156Arg (odds ratio = 1.05, 95% confidence interval: 0.91-1.22, P = .57) polymorphisms do not increase the risk of prostate cancer in the dominant model. Further, in the subgroup analysis by ethnicity, no relationships were observed between Lys751Gln and Arg156Arg polymorphisms and prostate cancer risk. However, stratified analysis by ethnicity revealed that Asp312Asn affects African (odds ratio = 1.57, 95% confidence interval: 1.06-2.33, P = .382) and Asian populations (odds ratio = 2.09, 95% confidence interval: 1.39-3.14, P = .396) in homozygote comparison. In conclusion, this meta-analysis suggests that there is no general association between the Asp312Asn, Lys751Gln, and Arg156Arg polymorphisms in XPD and prostate cancer susceptibility.

Association between the ERCC2 Asp312Asn polymorphism and risk of cancer.

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. The relationship between genetic polymorphisms and the risk of cancers has been widely researched. Excision repair cross-complementing group 2 (ERCC2) gene plays important roles in the nucleotide excision repair pathway. There is contrasting evidence on the association between the ERCC2 Asp312Asn polymorphism and the risk of cancer. We conducted a comprehensive meta-analysis in order to assess the correlation between these factors. We searched the PubMed, EMBASE, Science Direct, Web of Science, and CNKI databases for studies published from January 1, 2005 to January 1, 2016. Finally, 86 articles with 38,848 cases and 48,928 controls were included in the analysis. The overall analysis suggested a significant association between the ERCC2 Asp312Asn polymorphism and cancer risk. Furthermore, control source, ethnicity, genotyping method, and cancer type were used for subgroup analysis. The result of a trial sequential analysis indicated that the cumulative evidence is adequate; hence, further trials were unnecessary in the overall analysis for homozygote comparison. In summary, our results suggested that ERCC2 Asp312Asn polymorphism is associated with increased cancer risk. A significantly increased cancer risk was observed in Asian populations, but not in Caucasian populations. Furthermore, the ERCC2 Asp312Asn polymorphism is associated with bladder, esophageal, and gastric cancers, but not with breast, head and neck, lung, prostate, and skin cancers, and non-Hodgkin lymphoma. Further multi-center, well-designed studies are required to validate our results.