International Lung Cancer Consortium: Pooled Analysis of Sequence Variants in DNA Repair and Cell Cycle Pathways
- Rayjean J. Hung1,2,
- David C. Christiani4,
- Angela Risch5,
- Odilia Popanda5,
- Aage Haugen6,
- Shan Zienolddiny6,
- Simone Benhamou7,8,
- Christine Bouchardy9,
- Qing Lan10,
- Margaret R. Spitz11,
- H.-Erich Wichmann12,13,
- Loic LeMarchand14,
- Paolo Vineis15,
- Giuseppe Matullo16,
- Chikako Kiyohara17,
- Zuo-Feng Zhang18,
- Benhnaz Pezeshki18,
- Curtis Harris10,
- Leah Mechanic10,
- Adeline Seow19,
- Daniel P.K. Ng19,
- Neonila Szeszenia-Dabrowska20,
- David Zaridze21,
- Jolanta Lissowska22,
- Peter Rudnai23,
- Eleonora Fabianova24,
- Dana Mates25,
- Lenka Foretova26,
- Vladimir Janout27,
- Vladimir Bencko28,
- Neil Caporaso10,
- Chu Chen29,
- Eric J. Duell1,
- Gary Goodman29,
- John K. Field30,
- Richard S. Houlston31,
- Yun-Chul Hong32,
- Maria Teresa Landi10,
- Philip Lazarus33,
- Joshua Muscat33,
- John McLaughlin3,
- Ann G. Schwartz34,
- Hongbing Shen35,
- Isabelle Stucker36,
- Kazuo Tajima37,
- Keitaro Matsuo37,
- Michael Thun38,
- Ping Yang39,
- John Wiencke40,
- Angeline S. Andrew41,
- Stephanie Monnier1,
- Paolo Boffetta1 and
- Paul Brennan1
- 1IARC, Lyon, France; 2Samuel Lunenfeld Research Institute of Mount Sinai Hospital; 3Cancer Care Ontario, Toronto, Ontario, Canada; 4Harvard University, Boston, Massachusetts; 5German Cancer Research Center, Heidelberg, Germany; 6National Institute of Occupational Health, Oslo, Norway; 7INSERM U794, Fondation Jean Dausset CEPH, Paris, France; 8CNRS FRE2939, Institut Gustave Roussy, Villejuif, France; 9Cancer Registry, Geneva, Switzerland; 10National Cancer Institute, Rockville; 11The University of Texas M. D. Anderson Cancer Center, Houston, Texas; 12GSF-National Research Center for Environment and Health, Neuherberg, Germany; 13IBE, University of Munich, Germany; 14University of Hawaii, Hawaii, Honolulu; 15Imperial College, London, United Kingdom; 16University of Turin, Turin, Italy; 17Kyushu University, Fukuoka, Japan; 18University of California at Los Angeles, Los Angeles, California; 19National University of Singapore, Singapore, Singapore; 20Department of Epidemiology, Institute of Occupational Medicine, Lodz, Poland; 21Institute of Carcinogenesis, Cancer Research Centre, Moscow, Russia; 22Department of Cancer Epidemiology and Prevention, The M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; 23National Institute of Environmental Health, Fodor József National Center for Public Health, Budapest, Hungary; 24Regional Authority of Public Health, Banská Bystrica, Slovakia; 25Institute of Public Health, Bucharest, Romania; 26Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic; 27Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic; 28Charles University of Prague, First Faculty of Medicine, Institute of Hygiene and Epidemiology, Prague, Czech Republic; 29Fred Hutchinson Cancer Research Center, Seattle, Washington; 30Roy Castle Lung Cancer Research Programme, Cancer Research Centre, The University of Liverpool, Liverpool, United Kingdom; 31Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom; 32Seoul National University College of Medicine, Seoul, Korea; 33Penn State College of Medicine, Hershey, Pennsylvania; 34Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan; 35Nanjing Medical University School of Public Health, Nanjing, People's Republic of China; 36INSERM U754 and UMR-S754, IFR69, Villejuif, France; 37Aichi Cancer Center Research Institute, Aichi, Japan; 38American Cancer Society, Atlanta, Georgia; 39Mayo Clinic Cancer Center, Rochester, Minnesota; 40University of California at San Francisco, San Francisco, California; and 41Dartmouth Medical School, Lebanon, New Hampshire
- Requests for reprints:
Paolo Boffetta, IARC, 150 cours Albert Thomas, 69008 Lyon, France. Phone: 33-47273-8441; Fax: 33-47273-8320. E-mail: boffetta{at}iarc.fr
Abstract
Background: The International Lung Cancer Consortium was established in 2004. To clarify the role of DNA repair genes in lung cancer susceptibility, we conducted a pooled analysis of genetic variants in DNA repair pathways, whose associations have been investigated by at least 3 individual studies.
Methods: Data from 14 studies were pooled for 18 sequence variants in 12 DNA repair genes, including APEX1, OGG1, XRCC1, XRCC2, XRCC3, ERCC1, XPD, XPF, XPG, XPA, MGMT, and TP53. The total number of subjects included in the analysis for each variant ranged from 2,073 to 13,955 subjects.
Results: Four of the variants were found to be weakly associated with lung cancer risk with borderline significance: these were XRCC3 T241M [heterozygote odds ratio (OR), 0.89; 95% confidence interval (95% CI), 0.79-0.99 and homozygote OR, 0.84; 95% CI, 0.71-1.00] based on 3,467 cases and 5,021 controls from 8 studies, XPD K751Q (heterozygote OR, 0.99; 95% CI, 0.89-1.10 and homozygote OR, 1.19; 95% CI, 1.02-1.39) based on 6,463 cases and 6,603 controls from 9 studies, and TP53 R72P (heterozygote OR, 1.14; 95% CI, 1.00-1.29 and homozygote OR, 1.20; 95% CI, 1.02-1.42) based on 3,610 cases and 5,293 controls from 6 studies. OGG1 S326C homozygote was suggested to be associated with lung cancer risk in Caucasians (homozygote OR, 1.34; 95% CI, 1.01-1.79) based on 2,569 cases and 4,178 controls from 4 studies but not in Asians. The other 14 variants did not exhibit main effects on lung cancer risk.
Discussion: In addition to data pooling, future priorities of International Lung Cancer Consortium include coordinated genotyping and multistage validation for ongoing genome-wide association studies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3081–9)
Footnotes
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Grant support: National Cancer Institute R03 grant CA119704.
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- Accepted August 12, 2008.
- Received May 6, 2008.
- Revision received July 28, 2008.
