Systematic Evaluation of Apoptotic Pathway Gene Polymorphisms and Lung Cancer Risk
Menée initialement sur 661 cas de cancer du poumon et 959 témoins, puis validée sur une cohorte de 1 154 cas et 1 373 témoins, cette étude évalue l'association entre des polymorphismes à simple nucléotide de gènes impliqués dans la régulation de l'apoptose et le risque de cancer du poumon
We adopted a two-stage study design to screen 927 SNPs located in 73 apoptotic-pathway genes in a case-control study and then performed a fast-track validation of the significant SNPs in a replication population to identify sequence variations in the apoptotic pathway modulating lung cancer risk. Fifty-five SNPs showed significant associations in the discovery population comprised of 661 lung cancer cases and 959 controls. Six of these SNPs located in three genes (BCL2, CASP9 and ANKS1B) were validated in a replication population with 1,154 cases and 1,373 controls. Additive model was the best-fitting model for five SNPs (rs1462129 and rs255102 of BCL2, rs6685648 of CASP9 and rs1549102, rs11110099 of ANKS1B) and recessive model was the best fit for one SNP (rs10745877 of ANKS1B). In the analysis of joint effects with subjects carrying no unfavorable genotypes as the reference group, those carrying one, two, and three or more unfavorable genotypes had an OR of 2.22 (95% CI=1.08-4.57, P=0.03), 2.70 (95% CI=1.33-5.49; P=0.006), and 4.13 (95% CI=2.00-8.57; P=0.0001), respectively (P for trend=6.05E-06). The joint effect of unfavorable genotypes was also validated in the replication population. The SNPs identified are located in or near key genes known to play important roles in apoptosis regulation, supporting the strong biological relevance of our findings. Future studies are needed to identify the causal SNPs and elucidate the underlying molecular mechanisms.
http://carcin.oxfordjournals.org/content/early/2012/06/03/carcin.bgs192.abstract