Meta-analysis of new genome-wide association studies of colorectal cancer risk

被引：174

作者：

Peters, Ulrike ^{[1
,2
]}

Hutter, Carolyn M. ^{[1
]}

Hsu, Li ^{[3
]}

Schumacher, Fredrick R. ^{[4
]}

Conti, David V. ^{[4
]}

Carlson, Christopher S. ^{[1
]}

Edlund, Christopher K.

Haile, Robert W. ^{[4
]}

Gallinger, Steven ^{[5
]}

Zanke, Brent W. ^{[6
]}

Lemire, Mathieu ^{[7
]}

Rangrej, Jagadish ^{[7
]}

Vijayaraghavan, Raakhee ^{[8
]}

Chan, Andrew T. ^{[9
,10
,11
]}

Hazra, Aditi ^{[10
,11
,12
]}

Hunter, David J. ^{[12
]}

Ma, Jing ^{[10
,11
]}

Fuchs, Charles S. ^{[10
,11
,13
]}

Giovannucci, Edward L. ^{[10
,11
,14
]}

Kraft, Peter ^{[12
]}

Liu, Yan ^{[15
]}

Chen, Lin ^{[16
]}

Jiao, Shuo ^{[1
]}

Makar, Karen W. ^{[1
]}

Taverna, Darin ^{[8
]}

Gruber, Stephen B. ^{[17
]}

Rennert, Gad ^{[18
,19
]}

Moreno, Victor ^{[20
]}

Ulrich, Cornelia M. ^{[1
,2
,21
]}

Woods, Michael O. ^{[22
]}

Green, Roger C. ^{[22
]}

Parfrey, Patrick S. ^{[23
]}

Prentice, Ross L. ^{[24
]}

Kooperberg, Charles ^{[24
]}

Jackson, Rebecca D. ^{[25
]}

LaCroix, Andrea Z. ^{[1
]}

Caan, Bette J. ^{[26
]}

Hayes, Richard B. ^{[27
]}

Berndt, Sonja I. ^{[28
]}

Chanock, Stephen J. ^{[28
]}

Schoen, Robert E. ^{[29
]}

Chang-Claude, Jenny ^{[30
]}

Hoffmeister, Michael ^{[31
]}

Brenner, Hermann ^{[31
]}

Frank, Bernd ^{[31
]}

Bezieau, Stephane ^{[32
]}

Kuery, Sebastien ^{[32
]}

Slattery, Martha L. ^{[33
]}

Hopper, John L. ^{[34
]}

Jenkins, Mark A. ^{[34
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA

[2] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA

[3] Fred Hutchinson Canc Res Ctr, Biostat & Biomath Program, Seattle, WA 98104 USA

[4] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[5] Toronto Gen Hosp, Univ Hlth Network, Dept Surg, Toronto, ON, Canada

[6] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada

[7] Ontario Inst Canc Res, Toronto, ON, Canada

[8] Translat Genom Res Inst, Phoenix, AZ USA

[9] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA

[10] Harvard Univ, Sch Med, Boston, MA USA

[11] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA

[12] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

[13] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[14] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[15] Stephens & Associates, Dallas Res Ctr, Dallas, TX USA

[16] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA

[17] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[18] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel

[19] Technion Fac Med, Haifa, Israel

[20] Catalan Inst Oncol IDIBELL, Biostat & Bioinformat Unit, Barcelona, Spain

[21] German Canc Res Ctr, Div Prevent Oncol, D-6900 Heidelberg, Germany

[22] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada

[23] Mem Univ Newfoundland, Fac Med, Discipline Med, St John, NF, Canada

[24] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA

[25] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA

[26] Kaiser Permanente Med Care Program, Div Res, Oakland, CA USA

[27] NYU, Dept Environm Med, Sch Med, Div Epidemiol, New York, NY 10016 USA

[28] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA

[29] Univ Pittsburgh, Dept Epidemiol, Med Ctr, Pittsburgh, PA 15261 USA

[30] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany

[31] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany

[32] Ctr Hosp Univ CHU Nantes, Serv Genet Med, Nantes, France

[33] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA

[34] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[35] Univ Hawaii Manoa, Program Epidemiol, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA

[36] Mayo Clin, Dept Med Genet, Rochester, MN USA

[37] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA

[38] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[39] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

来源：

HUMAN GENETICS | 2012年 / 131卷 / 02期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

SUSCEPTIBILITY LOCI; RARE VARIANTS; COMMON; 8Q24; SCAN; INFERENCE; GENE; FUTURE; TERT;

D O I：

10.1007/s00439-011-1055-0

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 x 10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 x 10(-5)). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 x 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.

引用

页码：217 / 234

页数：18

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