Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways.

Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways. Research Abstract Details 

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Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways. Abstract Text:

Rayjean J Hung,Meili Baragatti,Duncan Thomas,James McKay,Neonila Szeszenia-Dabrowska,David Zaridze,Jolanta Lissowska,Peter Rudnai,Eleonora Fabianova,Dana Mates,Lenka Foretova,Vladimir Janout,Vladimir Bencko,Amelie Chabrier,Norman Moullan,Federico Canzian,Janet Hall,Paolo Boffetta,Paul Brennan,Rayjean J Hung,Meili Baragatti,Duncan Thomas,James McKay,Neonila Szeszenia-Dabrowska,David Zaridze,Jolanta Lissowska,Peter Rudnai,Eleonora Fabianova,Dana Mates,Lenka Foretova,Vladimir Janout,Vladimir Bencko,Amelie Chabrier,Norman Moullan,Federico Canzian,Janet Hall,Paolo Boffetta,Paul Brennan,

The DNA repair systems maintain the integrity of the human genome and cell cycle checkpoints are a critical component of the cellular response to DNA damage. We hypothesized that genetic variants in DNA repair and cell cycle control pathways will influence the predisposition to lung cancer, and studied 27 variants in 17 DNA repair enzymes and 10 variants in eight cell cycle control genes in 1,604 lung cancer patients and 2,053 controls. To improve the estimation of risks for specific variants, we applied a Bayesian approach in which we allowed the prior knowledge regarding the evolutionary biology and physicochemical properties of the variant to be incorporated into the hierarchical model. Based on the estimation from the hierarchical modeling, subjects who carried OGG1 326C/326C homozygotes, MGMT 143V or 178R, and CHEK2 157I had an odds ratio of lung cancer equal to 1.45 [95% confidence interval (95% CI), 1.05-2.00], 1.18 (95% CI, 1.01-1.40), and 1.58 (95% CI, 1.14-2.17). The association of CHEK2 157I seems to be overestimated in the conventional analysis. Nevertheless, this association seems to be robust in the hierarchical modeling. None of the pathways seem to have a prominent effect. In general, our study supports the notion that sequence variation may explain at least some of the variation of inherited susceptibility. In particular, further investigation of OGG1, MGMT, and CHEK2 focusing on the genetic regions where the present markers are located or the haplotype blocks tightly linked with these markers might be warranted. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2736-44).

Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways. Publishing Authors By Initials

RJ Hung,M Baragatti,D Thomas,J McKay,N Szeszenia-Dabrowska,D Zaridze,J Lissowska,P Rudnai,E Fabianova,D Mates,L Foretova,V Janout,V Bencko,A Chabrier,N Moullan,F Canzian,J Hall,P Boffetta,P Brennan,RJ Hung,M Baragatti,D Thomas,J McKay,N Szeszenia-Dabrowska,D Zaridze,J Lissowska,P Rudnai,E Fabianova,D Mates,L Foretova,V Janout,V Bencko,A Chabrier,N Moullan,F Canzian,J Hall,P Boffetta,P Brennan,

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Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cancer epidemiology, biomarkers & prevention : a p

VOLUME: 16

Page Numbers: 2736-44

Journal Abbreviation: Cancer Epidemiol. Biomarkers P

ISSN: 1055-9965

DAY: 18

MONTH: Dec

YEAR: 2007

Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways.

AFFILIATION: IARC, 150 cours Albert Thomas, F-69372 Lyon Cedex 08, France. hung@iarc.fr.

Country: United States

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MEDLINETA: Cancer Epidemiol Biomarkers Pr

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