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 codin...

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Bibliographic Details
Published in:	Cancer letters Vol. 278; no. 2; pp. 183 - 191
Main Authors:	Ulybina, Yulia M, Kuligina, Ekatherina Sh, Mitiushkina, Nathalia V, Rozanov, Maxim E, Ivantsov, Alexandr O, Ponomariova, Daria N, Togo, Alexandr V, Levchenko, Evgeny V, Shutkin, Vladimir A, Brenister, Sergiu I, Devilee, Peter, Zhivotovsky, Boris, Hirvonen, Ari, Imyanitov, Evgeny N
Format:	Journal Article
Language:	English
Published:	Ireland Elsevier B.V 18-06-2009 Elsevier Limited
Subjects:	Adult Age Aged Aged, 80 and over Apoptosis Caspase 8 - genetics Caspases - genetics Confidence intervals Deoxyribonucleic acid DNA DNA repair Gene polymorphisms Genes Genetic Predisposition to Disease Genetic testing Hematology, Oncology and Palliative Medicine Humans Lung cancer Lung Neoplasms - etiology Lung Neoplasms - genetics Medicin och hälsovetenskap Middle Aged Mortality Polymorphism, Single Nucleotide Predisposition Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor - genetics Smoking Studies Gene polymorphisms Lung cancer Predisposition Apoptosis
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0304-3835 1872-7980 1872-7980
DOI:	10.1016/j.canlet.2009.01.012