Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia

被引：31

作者：

Cheng, Iona ^{[1
]}

Kocarnik, Jonathan M. ^{[2
]}

Dumitrescu, Logan ^{[3
,4
,5
]}

Lindor, Noralane M. ^{[6
]}

Chang-Claude, Jenny ^{[7
]}

Avery, Christy L. ^{[8
]}

Caberto, Christian P. ^{[9
]}

Love, Shelly-Ann ^{[8
]}

Slattery, Martha L. ^{[10
]}

Chan, Andrew T. ^{[11
,12
]}

Baron, John A. ^{[13
]}

Hindorff, Lucia A. ^{[14
]}

Park, Sungshim Lani ^{[9
]}

Schumacher, Fredrick R. ^{[15
]}

Hoffmeister, Michael ^{[16
]}

Kraft, Peter ^{[17
]}

Butler, Anne M. ^{[8
]}

Duggan, David J. ^{[18
]}

Hou, Lifang ^{[19
]}

Carlson, Chris S. ^{[2
]}

Monroe, Kristine R. ^{[15
]}

Lin, Yi ^{[2
]}

Carty, Cara L. ^{[2
]}

Mann, Sue ^{[2
]}

Ma, Jing ^{[11
]}

Giovannucci, Edward L. ^{[11
,20
]}

Fuchs, Charles S. ^{[11
,21
]}

Newcomb, Polly A. ^{[2
]}

Jenkins, Mark A. ^{[22
]}

Hopper, John L. ^{[22
]}

Haile, Robert W. ^{[23
]}

Conti, David V. ^{[15
]}

Campbell, Peter T. ^{[24
]}

Potter, John D. ^{[2
,25
]}

Caan, Bette J. ^{[26
]}

Schoen, Robert E. ^{[27
]}

Hayes, Richard B. ^{[28
]}

Chanock, Stephen J. ^{[29
]}

Berndt, Sonja I. ^{[29
]}

Kuery, Sebastien ^{[30
]}

Bezieau, Stephane ^{[30
]}

Ambite, Jose Luis ^{[31
]}

Kumaraguruparan, Gowri ^{[31
]}

Richardson, Danielle M. ^{[6
]}

Goodloe, Robert J. ^{[5
]}

Dilks, Holli H. ^{[5
,32
]}

Baker, Paxton ^{[5
]}

Zanke, Brent W. ^{[33
]}

Lemire, Mathieu ^{[34
]}

Gallinger, Steven ^{[35
,36
]}

机构：

[1] Canc Prevent Inst Calif, Fremont, CA 94538 USA

[2] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA

[3] Vanderbilt Univ, Dept Mol Physiol, Nashville, TN 37235 USA

[4] Vanderbilt Univ, Dept Biophys, Nashville, TN 37235 USA

[5] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA

[6] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ 85260 USA

[7] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[8] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[9] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA

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

[11] Brigham & Womens Hosp & Harvard, Dept Med, Channing Div Network Med, Boston, MA USA

[12] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA

[13] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA

[14] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA

[15] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA

[16] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

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

[18] Translat Genom Res Inst, Div Genet Basis Human Dis, Phoenix, AZ USA

[19] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA

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

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

[22] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[23] Stanford Canc Inst, Palo Alto, CA USA

[24] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[25] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand

[26] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA

[27] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA 15260 USA

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

[29] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[30] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France

[31] Univ So Calif, Informat Sci Inst, Marinadel Rey, CA USA

[32] Vanderbilt Univ, Vanderbilt Technol Adv Genom, Nashville, TN 37235 USA

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

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

[35] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[36] Mt Sinai Hosp, Dept Surg, Toronto, ON M5G 1X5, Canada

[37] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

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

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

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

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

[42] Germany German Canc Consortium DKTK, Heidelberg, Germany

[43] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37235 USA

来源：

GUT | 2014年 / 63卷 / 05期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; PROSTATE-CANCER; MULTIPLE LOCI; COLON-CANCER; IDENTIFIES; 8Q24; BREAST; COHORT; SCAN;

D O I：

10.1136/gutjnl-2013-305189

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Objective Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92x10(-4) was used to determine statistical significance of the associations. Results Two correlated SNPs-rs10090154 and rs4242382-in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p = 1.74x10(-5)), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.

引用

页码：800 / 807

页数：8

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