Identifying common genetic variants associated with disease risk and clinical outcome in epithelial ovarian cancer

摘要: Combinations of common germline low-moderate susceptibility alleles may be responsible for some the 90% ovarian cancer (OC) cases not explained by known risk genes. These also affect survival OC patients. The effects 34 tagging single nucleotide polymorphisms (tSNPs) from candidate oncogenes (BRAF, ERBB2, KRAS, NMI and PIK3CA) 63 tSNPs from “functionally” relevant genes (AIFM2, AKTIP, AXIN2, CASP5, FILIP1L, RBBP8, RGC32, RUVBL1 STAG3) on sufferers were evaluated with ~1,800 3,045 controls. Associations found between disease risk and rs11683487 (P-dominant=0.004) rs13063604 (P-trend=0.0192). These associations independently validated with additional samples, however, they remained significant when results both stages genotyping were combined (P<0.05). Global tests association significant for BRAF, CASP5 (P-global<0.05). However, there was no evidence an excess 340 SNPs investigated with the admixture maximum likelihood test (P-trend=0.068). BRAF, RBBP8 associated survival of all When analysis restricted to 4 main histological subtypes OC, identified. Although these are of particular interest, based relatively small numbers samples and have been corrected multiple testing, therefore should be treated caution. The secondary objective project, evaluate whole genome amplification (WGA) DNA SNP multiplex platforms, are also described. To conclude, identified candidate oncogenes and functionally cancer. The performance WGA genotyping platforms highlighted the importance comparing corresponding gDNA in order to ascertain quality platform.