Fig. 1

rs1800734 shows no evidence of association with endometrial cancer risk, MLH1 promoter methylation or MLH1 gene expression. a A forest plot showing a meta-analysis of four rs1800734 endometrial cancer association analyses performed on MSI cases (overall cases = 225, overall controls = 13582). The plot shows the odds ratio [upper 95% CI, lower 95% CI] of the respective studies. Diamond indicates overall odds ratio and 95% confidence interval with the p values generated from a fixed-effects meta-analysis showing no evidence of an association for the rs1800734 SNP with MSI endometrial cancer (p = 0.6). Studies included are as follows: (1) ANECS-Illumina genotyped, (2) ANECS-ICOGS genotyped, (3) RENDOCAS and (4) MCCS. b A forest plot showing a meta-analysis of four rs1800734 endometrial cancer association analyses performed on MSI cases which show loss of MLH1/PMS2 proteins but not those showing loss of MSH2/MSH6 (overall cases = 157, overall controls = 13582). The plot shows the odds ratio [upper 95% CI, lower 95% CI] of the respective studies. Diamond indicates overall odds ratio and 95% confidence interval with the p values generated from a fixed-effects meta-analysis showing no evidence of an association for the rs1800734 SNP with endometrial cancer with loss of MLH1/PMS2 (p = 0.42). Studies included are as follows: (1) ANECS-Illumina genotyped, (2) ANECS-ICOGS genotyped, (3) RENDOCAS and (4) MCCS. Interestingly, in the RENDOCAS study, rs1800734 does show a significant association with EC; however, this is based on 25 cases only. c A boxplot of the proportion of methylation proximal to the MLH1 promoter and MLH1 gene expression in EC patient samples (TCGA-UCEC) stratified by rs1800734 genotype and MSI/MSS status. Methylation beta (β) indicates the median proportion of methylated to unmethylated reads of 3 CpG probes proximal to MLH1 (probe names: cg00893636, cg02279071, cg13846866). Relative expression (FPKM-UQ) indicates fragments per kilobase of MLH1 per million mapped reads upper quartile. Plots show the median, upper and lower quartile of expression or methylation stratified by MSI status and rs1800734 genotype (MSI n = 206, MSS n = 349). rs1800734 genotype had no significant effect on methylation (p = 0.556 MSS, p = 0.585 MSI; Kruskal-Wallis) or expression (p = 0.434 MSI, Kruskal-Wallis) except for a small set of MSS ECs with AA genotype (n = 7) in which expression was significantly higher than MSS ECs with the GG genotype (p = 0.045, pairwise Wilcoxon). The biological significance of this is uncertain