Coding polymorphisms in Casp5, Casp8 and DR4 genes may play a role in predisposition to lung cancer.

Abstract:

: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 significance (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 modifiers.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Ulybina YM,Kuligina ES,Mitiushkina NV,Rozanov ME,Ivantsov AO,Ponomariova DN,Togo AV,Levchenko EV,Shutkin VA,Brenister SI,Devilee P,Zhivotovsky B,Hirvonen A,Imyanitov EN

doi

10.1016/j.canlet.2009.01.012

subject

Has Abstract

pub_date

2009-06-18 00:00:00

pages

183-191

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(09)00025-1

journal_volume

278

pub_type

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