Apoptoza joacă un rol important în eliminarea celulelor ADN-deteriorate, protejând astfel gazda de la dezvoltarea cancerului. Unele date indică faptul că variaţiile normale în secvenţa de gene apoptotic poate duce la capacitatea de apoptotic suboptimal şi, prin urmare, la creşterea riscului de cancer. Am testat 19 secvenţe de codifi care SNP apoptotic, în 2 etape studiu epidemiologic molecular. Pentru sortarea preliminară a candidaţilor SNP, am utlizat o ,,comparaţie a extremelor”.

Apoptosis plays a role in the elimination of DNA-damaged cells thus protecting the host from cancer development. Some data indicate that normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk. We tested 19 coding apoptotic gene SNPs in 2-stage molecular epidemiological study. For the preliminary sorting of SNP candidates, we employed a ,,comparison of extremes” approach, where 111 patients with highly pronounced LC susceptibility (non-smokers or young-onset light smokers) were analyzed against 110 subjects with the evidence for LC tolerance (elderly tumor-free heavy smokers). Three genotypes demonstrated possible association with LC risk (Leu/Leu-homozygotes for Casp5 Val318Leu versus other genotypes: OR = 2.47 (95% CI: 1.07 – 5.69), p = 0.03; His-carriers for Casp8 His302Asp: OR = 2.26 (95% CI: 1.18 - 4.31), p = 0.02; Arg-carriers for DR4 Lys441Arg: OR = 1.89 (95% CI: 1.05 – 3.40), p = 0.03), and therefore were selected for the validation. The extended study included 2 case-control series, namely subjects from Russia (351 LC cases and 538 controls) and Moldova (296 LC cases and 295 controls). Interestingly, all three candidate genotypes consistently demonstrated OR above 1 both in Russian and in Moldovian groups. Although the combined Mantel-Haenszel analysis yet failed to reach statistical signifi cance (OR = 1.22 (95% CI: 0.90 - 1.65), p = 0.21; OR = 1.17 (95% CI: 0.92 - 1.50), p = 0.21; OR = 1.19 (95% CI: 0.95 - 1.51), p = 0.14, respectively), the obtained data indicate that Casp5, Casp8 and DR4 gene polymorphisms may deserve consideration in large-scale case-control studies of LC risk modifi ers.