Evidence of gene-gene interactions in lung carcinogenesis in a large pooled analysis

Paolo Vineis, Sisko Anttila, Simone Benhamou, Monica Spinola, Ari Hirvonen, Chikako Kiyohara, Seymour I. Garte, Riccardo Puntoni, Agneta Rannug, Richard C. Strange, Emanuela Taioli

研究成果: ジャーナルへの寄稿記事

35 引用 (Scopus)

抄録

To test the hypothesis of interaction among genetic variants in increasing the individual risk of cancer, we have studied the cumulative effect on lung cancer risk of variants in three metabolic genes, CYP1A1, GSTM1 and GSTT1, which are involved in the metabolism of the tobacco smoke constituents and environmental contaminants, polycyclic aromatic hydrocarbons and of other lung carcinogens. We have selected from the Genetic Susceptibility to Environmental Carcinogens pooled analysis all the studies on lung cancer conducted after 1991 in which all variants were available. The data set includes 611 cases and 870 controls. We found a cumulative effect of the combination of the a priori 'at-risk' alleles for these genes (P for trend 0.004). The risk of lung cancer was increased with the combination of CYP1A1*2B or CYP1A1*4 alleles and the double deletion of both GSTM1 and GSTT1 up to an odds ratio (OR) of 8.25 (95% confidence interval 2.29-29.77) for the combination including CYP1A1*4; among never smokers, the latter combination was associated with an OR of 16.19 (1.90-137). Estimates did not change after adjustment by the number of cigarettes smoked and duration of smoking were consistent across ethnicities and were approximately the same for adenocarcinomas and squamous cell carcinomas. These observations from a large pooled analysis strongly suggest the existence of gene-gene interactions in lung carcinogenesis. People with rare combinations of common gene variants have a high risk of cancer and can be assimilated to subjects with highly penetrant mutations.

元の言語英語
ページ(範囲)1902-1905
ページ数4
ジャーナルCarcinogenesis
28
発行部数9
DOI
出版物ステータス出版済み - 9 1 2007

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Cytochrome P-450 CYP1A1
Carcinogenesis
Lung
Lung Neoplasms
Genes
Alleles
Odds Ratio
Environmental Carcinogens
Social Adjustment
Polycyclic Aromatic Hydrocarbons
Genetic Predisposition to Disease
Smoke
Tobacco Products
Carcinogens
Tobacco
Squamous Cell Carcinoma
Neoplasms
Adenocarcinoma
Smoking
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Cancer Research

これを引用

Vineis, P., Anttila, S., Benhamou, S., Spinola, M., Hirvonen, A., Kiyohara, C., ... Taioli, E. (2007). Evidence of gene-gene interactions in lung carcinogenesis in a large pooled analysis. Carcinogenesis, 28(9), 1902-1905. https://doi.org/10.1093/carcin/bgm039

Evidence of gene-gene interactions in lung carcinogenesis in a large pooled analysis. / Vineis, Paolo; Anttila, Sisko; Benhamou, Simone; Spinola, Monica; Hirvonen, Ari; Kiyohara, Chikako; Garte, Seymour I.; Puntoni, Riccardo; Rannug, Agneta; Strange, Richard C.; Taioli, Emanuela.

:: Carcinogenesis, 巻 28, 番号 9, 01.09.2007, p. 1902-1905.

研究成果: ジャーナルへの寄稿記事

Vineis, P, Anttila, S, Benhamou, S, Spinola, M, Hirvonen, A, Kiyohara, C, Garte, SI, Puntoni, R, Rannug, A, Strange, RC & Taioli, E 2007, 'Evidence of gene-gene interactions in lung carcinogenesis in a large pooled analysis', Carcinogenesis, 巻. 28, 番号 9, pp. 1902-1905. https://doi.org/10.1093/carcin/bgm039
Vineis, Paolo ; Anttila, Sisko ; Benhamou, Simone ; Spinola, Monica ; Hirvonen, Ari ; Kiyohara, Chikako ; Garte, Seymour I. ; Puntoni, Riccardo ; Rannug, Agneta ; Strange, Richard C. ; Taioli, Emanuela. / Evidence of gene-gene interactions in lung carcinogenesis in a large pooled analysis. :: Carcinogenesis. 2007 ; 巻 28, 番号 9. pp. 1902-1905.
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AU - Kiyohara, Chikako

AU - Garte, Seymour I.

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