Journal Article

International Lung Cancer Consortium: Coordinated association study of 10 potential lung cancer susceptibility variants

Therese Truong, Wiebke Sauter, James D. McKay, H.Dean Hosgood, Carla Gallagher, Christopher I. Amos, Margaret Spitz, Joshua Muscat, Philip Lazarus, Thomas Illig, H.Erich Wichmann, Heike Bickeböller, Angela Risch, Hendrik Dienemann, Zuo-Feng Zhang, Behnaz Pezeshki Naeim, Ping Yang, Shanbeh Zienolddiny, Aage Haugen, Loïc Le Marchand, Yun-Chul Hong, Jin Hee Kim, Eric J. Duell, Angeline S. Andrew, Chikako Kiyohara, Hongbing Shen, Keitaro Matsuo, Takeshi Suzuki, Adeline Seow, Daniel P.K. Ng, Qing Lan, David Zaridze, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Vali Constantinescu, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Neil E. Caporaso, Demetrius Albanes, Michael Thun, Maria Teresa Landi, Joanna Trubicka, Marcin Lener, Jan Lubiński, Ying Wang, Amélie Chabrier, Paolo Boffetta, Paul Brennan and Rayjean J. Hung

in Carcinogenesis

Volume 31, issue 4, pages 625-633
Published in print April 2010 | ISSN: 0143-3334
Published online January 2010 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgq001
International Lung Cancer Consortium: Coordinated association study of 10 potential lung cancer susceptibility variants

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Background. Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Methods. Genotype data from 15 ILCCO case–control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results. Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 × 10−4). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11 722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89–0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85–0.95), P = 1 × 10−4]. Conclusion. This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations.

Journal Article.  5281 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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