Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65-1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.
Bibliographical noteFunding Information:
ANECS was supported by project grants from the National Health and Medical Research Council (NHMRC) of Australia (ID#339435), The Cancer Council Queensland (ID#4196615) and Cancer Council Tasmania (ID#403031 and ID#457636). ABS and PMW are supported by NHMRC Senior Research Fellowships. TOM is supported by an Australian Postgraduate Award, an Institute of Health and Biomedical Innovation PhD Top-Up and a Smart State PhD Award. PECS was funded by the intramural research program at the US National Cancer Institute, Division of Cancer Epidemiology and Genetics in the Hormonal and Reproductive Epidemiology Branch. SEARCH was funded by Cancer Research UK grants [C490/A11021, C8197/A10123, C1287/A7497, C1287/A10118], BCC grant [2077NovPR17] and EU FP7 COGS [HEALTH-F2-2009-223175]. AMD was supported by Cancer Research Grant [C8197/A10865] and The Joseph Mitchell Trust.
- Endometrial cancer
- Single nucleotide polymorphism