Abstract
Abstract Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. To investigate this hypothesis, we carried out a two-stage study to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 830 endometrial cancer cases and 2,322 controls using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (P<0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. We then selected one SNP from each of the 24 loci for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in the stage 2 sample, which consisted of eight additional studies including 4,890 endometrial cancer cases and 5,403 controls. Four of the 21 SNPs in or near the FABP1, CXCL3, MSR1, and MMP9 genes were significantly associated with endometrial cancer in the combined data sets. The allelic odds ratios were 0.90 (0.82-0.97) for FABP1, 1.17 (1.05-1.31) for CXCL3, 0.86 (0.78-0.96) for MSR1, and 0.90 (0.85-0.95) for MMP9. The SNPs in CXCL3 and MMP9 were significantly associated with endometrial cancer in both the discovery and replication samples. Of these findings, the association for the MMP9 promoter polymorphism rs3918249 (P=0.00047) remained significant after adjustment for the total number of comparisons. These findings suggest that genetic polymorphisms in the MMP9 gene and possibly in or near the FABP1, CXCL3, and MSR1 genes may contribute to genetic susceptibility to endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-331. doi:1538-7445.AM2012-LB-331
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