Identification of inherited genetic variations influencing prognosis in early onset breast cancer
Menée sur une cohorte de 536 patientes atteintes d'un cancer du sein avant l'âge de 40 ans, cette étude identifie un polymorphisme à simple nucléotide en amont du locus ARRDC3 en association avec le pronostic de la maladie
Genome Wide Association Studies (GWAs) have begun to investigate associations between inherited genetic variations and breast cancer prognosis. Here we report our findings from a GWAs conducted in 536 early onset breast cancer patients aged 40 or less at diagnosis and with a mean follow-up period of 4.1 years (S.D=1.96). Patients were selected from the POSH (Prospective study of Outcomes in Sporadic versus Hereditary breast cancer). A Bonferroni correction for multiple testing determined that a p-value of 1.0 x 10-7 was a statistically significant association signal. Following QC we identified 487496 SNPs for association tests in stage-1. In stage 2, 35 SNPs with the most significant associations were genotyped in 1516 independent cases from the same early onset cohort. In stage-2, 11 SNPs remained associated in the same direction (p≤0.05). Fixed effects meta-analysis models identified one SNP associated at close to genome wide level of significance 556 kb upstream of the ARRDC3 locus HR=1.61 (1.33-1.96, p=9.5 x 10-7). Four further associations at or close to the PBX1, RORα, NTN1 and SYT6 loci also came close to genome wide significance levels (p=10-6). In the first ever GWAS for identification of SNPs associated with prognosis in early onset breast cancer patients we report a SNP upstream of the ARRDC3 locus as potentially associated with prognosis (Median follow-up time for genotypes CC=4 years, CT=3 years and TT=2.7 years, Wilcoxon rank sum test CC vs. CT, p=4 x 10-4 and CT vs. TT, P=0.76). Four further loci might also be associated with prognosis
Cancer Research , résumé, 2013