The Genetic Association Between Igf Pathway Genes And HBV-Related HCC

Backgrounds: Hepatocellular carcinoma (HCC) is one of most common cancers andranks fifth among causes of cancer mortality worldwide. Variation in the risk of HCCis caused by a complex interplay between multiple genetic and environmental factors.The insulin-like growth factors (insulin-like growth factors, IGFs) pathway has beenimplicated as important mediators for the development of various types of cancers.Several functional polymorphisms in the IGFs pathway genes have been wellcharacterized. We examined whether the IGFs pathway polymorphisms were relatedto HCC risk in Chinese populations.Methods: To identify new susceptibility loci for HCC, we performed a two-stagecase-control study in Chinese populations. Seventeen polymorphisms in the IGF-1,IGF-2, IGF-1R, IGF-2R and IGFBP-3genes were genotyped in348chronic HBVcarriers with HCC and359chronic HBV carriers without HCC recruited fromGuangxi province in southern China. Then, the promising associated SNPs weregenotyped in the three additional independent samples, consisting of1534individuals with HCC and1000control subjects recruited from Beijing, Jiangsu andGuangdong province, respectively. The associations with the susceptibility to HCCwere estimated by logistic regression.Results: After adjusting multiple tests, We observed a statistically significantassociation between rs2229765in IGF-1R and HCC risk. Compared with thegenotypes containing G allele，the AA genotype of rs2229765was associated with adecreased risk of HCC (OR=0.42;95%CI=0.24-0.71; P=0.00090in recessivemodel). This association， however，was not replicated in the three additionalindependent sample sets.Conclusions: Our findings suggest that the genetic polymorphisms in the IGF-1,IGF-2, IGF-1R, IGF-2R and IGFBP genes may not play a role in mediating thesusceptibility to HCC in Chinese populations.