Identification of common variants in BRCA2 and MAP2K4 for susceptibility to sporadic pancreatic cancer
Menée sur une cohorte initale de 981 cas et 1 991 témoins, puis sur une seconde cohorte de 2 603 cas et 2 877 témoins, cette étude chinoise identifie des variants des gènes BRCA2 et MAP2K4 en association avec la susceptibilité au cancer du pancréas
Germline mutations in genes that cause hereditary syndromes are highly predisposed to familial pancreatic cancer. However, genetic susceptibility to sporadic pancreatic cancer is largely uncovered. We conducted a two-stage association study on pancreatic cancer that included 981 cases and 1,991 controls in the first stage followed by a second stage (2,603 cases and 2,877 controls). Using an approach based on candidate genes whose roles in pancreatic cancer have been well-known, we identified two new susceptibility loci. rs11571836 located in the BRCA2 3'-untranslated region was significantly associated with lower expression of BRCA2 transcript and increased pancreatic cancer risk [odds ratio (OR)=1.30, 95% confidence interval (CI)=1.14–1.47, P=7.64x10-5] in a recessive manner. rs12939944 located in the MAP2K4 intron was associated with decreased risk (OR=0.82, 95% CI=0.74–0.91, P=0.0001) in a dominant manner. Our results demonstrate for the first time that common variants in BRCA2 and MAP2K4 are susceptibility to sporadic pancreatic cancer.
http://carcin.oxfordjournals.org/content/early/2013/01/07/carcin.bgt004.abstract