Abstract
We genotyped 2 SNPs (rs3790844 T/C and rs3790843 G/A) in the NR5A2 gene that were identified in a genome-wide association study (GWAS) of pancreatic cancer in populations of mainly European ancestry, and we examined their associations with pancreatic cancer risk in a case-control study of 360 patients and 400 control subjects in Japan. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The SNPs were in linkage disequilibrium (r2 = 0.80). For rs3790843, the multivariable-adjusted OR was 0.75 (95% CI: 0.41–1.36) and 0.60 (95%CI: 0.33–1.08) for subjects with the AG and AA genotype, respectively, compared to subjects with the GG genotype. The per allele OR was 0.78 (0.62–0.99) (P = 0.046). For rs3790844, the multivariable-adjusted OR was 0.65 (95% CI: 0.37–1.14) and 0.47 (95%CI: 0.27–0.83) for subjects with the CT and CC genotype, respectively, compared to subjects with the TT genotype. The per allele OR was 0.70 (0.56–0.89) (P = 0.003). Our case-control study found that rs3790843 and rs3790844 in the NR5A2 gene are associated with pancreatic cancer risk in Japanese subjects. The direction of association is consistent with the prior findings from GWASs.
Highlights
We genotyped 2 single nucleotide polymorphisms (SNPs) in the NR5A2 gene that were identified in a genome-wide association study (GWAS) of pancreatic cancer in populations of mainly European ancestry, and we examined their associations with pancreatic cancer risk in a case-control study of 360 patients and 400 control subjects in Japan
Of the 5 highly significant single nucleotide polymorphisms (SNPs) on 1q32.1 that map to NR5A2, rs3790844 showed the strongest association with pancreatic cancer, with a per-allele odds ratios (ORs) of 0.77. rs3790843 was highly correlated with rs3790844 in the Pancreatic Cancer Consortium (PanScan) European controls (r2 = 0.59)[8]
These findings suggested that the positive result for rs3790844 was more “noteworthy”. In this genetic case-control association study, we genotyped 2 GWASs-identified SNPs in the NR5A2 gene and examined their association with pancreatic cancer risk. We found that they were associated with pancreatic cancer risk in these Japanese subjects
Summary
We genotyped 2 SNPs (rs3790844 T/C and rs3790843 G/A) in the NR5A2 gene that were identified in a genome-wide association study (GWAS) of pancreatic cancer in populations of mainly European ancestry, and we examined their associations with pancreatic cancer risk in a case-control study of 360 patients and 400 control subjects in Japan. Our case-control study found that rs3790843 and rs3790844 in the NR5A2 gene are associated with pancreatic cancer risk in Japanese subjects. 5 GWASs conducted in populations of European, Japanese, and Chinese ancestry have reported 17 loci associated with increased susceptibility[7,8,9,10,11]. Rs3790843 and rs3790844 in the NR5A2 gene have been replicated in a previous study involving subjects of mainly European ancestry[21], it remains unclear whether these 2 SNPs are associated with pancreatic cancer risk in Asian populations. We examined the association between 2 SNPs (rs3790843 and rs3790844) in the NR5A2 gene and the risk of pancreatic cancer using data collected from a genetic case-control association study of Japanese subjects
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