Published data around the association between the rs4072037A > G polymorphism

Published data around the association between the rs4072037A > G polymorphism and gastric cancer (GCa) risk were inconclusive. Chinese populations. (carriers will develop GCa, suggesting that other factors are also important in the etiology, such as tobacco smoking, alcohol use and dietary habits [4]. In addition, genetic factors for the GCa risk are important as well, because the success in identifying at-risk populations KU-55933 IC50 by associations between genetic variants and GCa risk is usually encouraging [5C8]; however, it is necessary to confirm those genetic factors that have been reported to be important in the etiology of GCa. The (has 712 SNPs as reported to the dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi_showRare=on&chooseRs=all&go=Go&locusId=4582), only 11 SNPs (Physique ?(Physique1A.)1A.) have actually been confirmed in the HapMap database, of which only rs4072037 KU-55933 IC50 has a MAF > 0.05, representing a block of 4 SNPs (Figure ?(Figure1B).1B). KU-55933 IC50 The rs4072037 A > G polymorphism is located in the 5 untranslated region (UTR) of the second exon of at chromosome 1q22, alters transcriptional regulation, and determines splice variants in [9]. Several studies reported an association between the rs4072037 A > G polymorphism and GCa risk [10C16], but the results were inconclusive, especially different by ethnic group and primary tumor site. To further confirm this reported association, we conducted a replication study in an Eastern Chinese population with a relatively larger sample KU-55933 IC50 with subgroup analysis. Furthermore, a meta-analysis was also performed to further validate the association. Physique 1 Reported SNPs RESULTS The characteristics of participants included in this hospital-based case-control study were described elsewhere [17], but one sample in cases and four samples in controls failed to be genotyped in the current study. Thus, the final analysis included 1,124 GCa cases and 1,192 cancer-free controls. Participants were well matched by age and Rabbit Polyclonal to Chk2 (phospho-Thr387) sex with more smokers and drinkers in the controls, but these variables were further adjusted in the following multivariate analysis. Table ?Table11 lists allele frequencies of the rs4072037 A > G SNP in cases and controls and the estimated association between this SNP and GCa risk. Overall, the G allele was associated with a decreased GC risk in the study populace [GG vs. AA, OR = 0.47, 95% CI = 0.31C0.73; AG/GG vs. AA, OR = 0.82, 95% CI = 0.68C0.99; GG vs. AA/AG, OR = 0.48, 95% CI = 0.32C0.74]. In the stratified analysis (Table ?(Table2),2), these associations remained significant in subgroups of age, tumor site, drinking and smoking status. Table 1 Logistic regression analysis of associations between the genotypes of MUC1 rs4072037 A > G and gastric cancer risk in an Eastern Chinese population Table 2 Stratification analysis for the association between rs4072037 A > G polymorphism and GC risk in an Eastern Chinese population Then, we performed a mini meta-analysis, including the present study, of eight studies with 7312 cases and 6112 controls [10C16]. The pooled data indicated that this G allele was strongly associated with a decreased GCa risk (Table ?(Table3:3: AG vs. AA: OR = 0.64, 95% CI = 0.54C0.77; GG vs. AA: OR = 0.55, 95% CI = 0.46C0.65; AG/GG vs. AA: OR = 0.63, 95% CI = 0.53C0.75, Figure ?Physique2;2; and GG vs. AA/AG: OR = 0.72, 95% CI = 0.62C0.84, Figure ?Figure3)3) without significant publication bias. However, significant heterogeneities across studies were present in these genetic models. Thus, we performed a sensitivity analysis to assess the effects of each study around the pooled results. The pooled ORs were not affected by omitting each of studies at a time (data not shown), which suggests that the overall results are strong. Table 3 Meta-analysis for the association between the rs4072037 A > G SNP and GCa risk Physique 2 Meta-analysis for the association between rs4072037 SNP and GCa risk in the dominant genetic model (random-effects model) Physique 3 Meta-analysis for the association between rs4072037 SNP and GCa risk in the recessive genetic model (fixed-effects model) DISCUSSION In addition to environmental and way of life factors for GCa risk, genetic factors are also important in identifying at-risk populations for primary prevention of GCa..