Association of Aspirin and NSAID Use With Risk of Colorectal Cancer According to Genetic Variants

被引：160

作者：

Nan, Hongmei ^{[1
,2
]}

Hutter, Carolyn M. ^{[3
]}

Lin, Yi ^{[4
]}

Jacobs, Eric J. ^{[5
]}

Ulrich, Cornelia M. ^{[4
,6
]}

White, Emily ^{[4
,7
]}

Baron, John A. ^{[8
]}

Berndt, Sonja I. ^{[9
]}

Brenner, Hermann ^{[10
,11
]}

Butterbach, Katja ^{[10
]}

Caan, Bette J. ^{[12
]}

Campbell, Peter T. ^{[5
]}

Carlson, Christopher S. ^{[4
]}

Casey, Graham ^{[13
]}

Chang-Claude, Jenny ^{[14
]}

Chanock, Stephen J. ^{[9
]}

Cotterchio, Michelle ^{[15
]}

Duggan, David ^{[16
]}

Figueiredo, Jane C. ^{[13
]}

Fuchs, Charles S. ^{[17
]}

Giovannucci, Edward L. ^{[18
]}

Gong, Jian ^{[4
]}

Haile, Robert W. ^{[13
]}

Harrison, Tabitha A. ^{[4
]}

Hayes, Richard B. ^{[19
]}

Hoffmeister, Michael ^{[10
]}

Hopper, John L. ^{[20
]}

Hudson, Thomas J. ^{[21
,22
]}

Jenkins, Mark A. ^{[20
]}

Jiao, Shuo ^{[4
]}

Lindor, Noralane M. ^{[23
]}

Lemire, Mathieu ^{[22
]}

Le Marchand, Loic ^{[24
]}

Newcomb, Polly A. ^{[4
]}

Ogino, Shuji ^{[17
,25
,26
]}

Pflugeisen, Bethann M. ^{[4
]}

Potter, John D. ^{[4
,27
]}

Qu, Conghui ^{[4
]}

Rosse, Stephanie A. ^{[4
]}

Rudolph, Anja ^{[14
]}

Schoen, Robert E. ^{[28
]}

Schumacher, Fredrick R. ^{[13
]}

Seminara, Daniela ^{[3
]}

Slattery, Martha L. ^{[29
]}

Thibodeau, Stephen N. ^{[30
,31
]}

Thomas, Fridtjof ^{[32
]}

Thornquist, Mark ^{[4
]}

Warnick, Greg S. ^{[4
]}

Zanke, Brent W. ^{[33
]}

Gauderman, W. James ^{[13
]}

机构：

[1] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA

[2] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA

[3] NHGRI, NIH, Bethesda, MD 20892 USA

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

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

[6] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA

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

[8] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA

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

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

[11] German Canc Consortium DKTK, Heidelberg, Germany

[12] Kaiser Permanente Med Care Program No Calif, Div Res, Oakland, CA USA

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

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

[15] Canc Care Ontario, Prevent & Canc Control, Toronto, ON, Canada

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

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

[18] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Div Network Med, Boston, MA 02115 USA

[19] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA

[20] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic 3010, Australia

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

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

[23] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA

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

[25] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[26] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

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

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

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

[30] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

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

[32] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Div Biostat & Epidemiol, Memphis, TN 38163 USA

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

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

[35] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA

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

来源：

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2015年 / 313卷 / 11期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

GENOME-WIDE ASSOCIATION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN E-2 BIOSYNTHESIS; COLON-CANCER; PIK3CA MUTATION; METAANALYSIS; CYCLOOXYGENASE-2; CHEMOPREVENTION; INTERLEUKIN-16; POLYMORPHISMS;

D O I：

10.1001/jama.2015.1815

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

IMPORTANCE Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. OBJECTIVE To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene x environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS Case-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent. EXPOSURES Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors. MAIN OUTCOMES AND MEASURES Colorectal cancer. RESULTS Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% Cl, 0.64-0.74]; P = 6.2 x 10(-28)) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P = 4.6 x 10(-9) for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61-0.70]; P =7.7 x 10(-33)) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% Cl, 1.27-2.81]; P = .002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P = 8.2 x 10(-9) for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P = 1.9 x 10(-30)) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% Cl, 0.78-1.20]; P = .76). CONCLUSIONS AND RELEVANCE In this genome-wide investigation of gene x environment interactions, use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer, and this association differed according to genetic variation at 2 SNPs at chromosomes 12 and 15. Validation of these findings in additional populations may facilitate targeted colorectal cancer prevention strategies.

引用

页码：1133 / 1142

页数：10

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