PTGS2 and IL6 genetic variation and risk of breast and prostate cancer: results from the Breast and Prostate Cancer Cohort Consortium (BPC3)

被引：68

作者：

Dossus, Laure ^{[1
]}

Kaaks, Rudolf ^{[1
]}

Canzian, Federico ^{[1
]}

Albanes, Demetrius ^{[2
]}

Berndt, Sonja I. ^{[2
]}

Boeing, Heiner ^{[3
]}

Buring, Julie ^{[4
]}

Chanock, Stephen J. ^{[2
]}

Clavel-Chapelon, Francoise ^{[5
,6
]}

Feigelson, Heather Spencer ^{[7
,8
]}

Gaziano, John M. ^{[9
]}

Giovannucci, Edward ^{[10
,11
,12
]}

Gonzalez, Carlos ^{[13
]}

Haiman, Christopher A. ^{[14
]}

Hallmans, Goran ^{[15
]}

Hankinson, Susan E. ^{[11
]}

Hayes, Richard B. ^{[3
,16
]}

Henderson, Brian E. ^{[14
]}

Hoover, Robert N. ^{[2
]}

Hunter, David J. ^{[17
]}

Khaw, Kay-Tee ^{[18
]}

Kolonel, Laurence N. ^{[19
]}

Kraft, Peter ^{[17
]}

Ma, Jing ^{[11
]}

Le Marchand, Loic ^{[18
]}

Lund, Eiliv ^{[20
]}

Peeters, Petra H. M. ^{[21
]}

Stampfer, Meir ^{[11
,12
]}

Stram, Dan O. ^{[14
]}

Thomas, Gilles ^{[3
,22
]}

Thun, Michael J. ^{[7
]}

Tjonneland, Anne ^{[23
]}

Trichopoulos, Dimitrios ^{[12
,24
]}

Tumino, Rosario ^{[25
]}

Riboli, Elio ^{[26
]}

Virtamo, Jarmo ^{[27
]}

Weinstein, Stephanie J. ^{[2
]}

Yeager, Meredith ^{[3
,28
]}

Ziegler, Regina G. ^{[2
]}

Cox, David G.

机构：

[1] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

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

[3] German Inst Human Nutr, Dept Epidemiol, D-14558 Postdam Rehbruecke, Nuthetal, Germany

[4] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02215 USA

[5] Inst Gustave Roussy, F-94805 Villejuif, France

[6] INSERM, ERI 20, EA 4045, F-94805 Villejuif, France

[7] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30303 USA

[8] Kaiser Permanente, Denver, CO 80237 USA

[9] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging,Dept Med, Boston, MA 02215 USA

[10] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA

[11] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA

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

[13] Catalan Inst Oncol ICO Idibell ISCIII RETICC, Unit Nutr Environm & Canc, Barcelona 08907, Spain

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

[15] Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden

[16] NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY 10012 USA

[17] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02215 USA

[18] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England

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

[20] Univ Tromso, Inst Community Med, N-9037 Tromso, Norway

[21] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands

[22] Ctr Leon Berard, INSERM, U590, F-69373 Lyon, France

[23] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark

[24] Hellen Hlth Fdn, Athens 11527, Greece

[25] Canc Registry Azienda Osped Civile MP Arezzo, I-97100 Ragusa, Italy

[26] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England

[27] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland

[28] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21702 USA

来源：

CARCINOGENESIS | 2010年 / 31卷 / 03期

关键词：

NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GROWTH-FACTOR-I; COX-2; GENE; INTERLEUKIN-6; POLYMORPHISMS; INFLAMMATION; ASSOCIATION; CYCLOOXYGENASE-2; PREVENTION; PREDICTORS;

D O I：

10.1093/carcin/bgp307

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Genes involved in the inflammation pathway have been associated with cancer risk. Genetic variants in the interleukin-6 (IL6) and prostaglandin-endoperoxide synthase-2 (PTGS2, encoding for the COX-2 enzyme) genes, in particular, have been related to several cancer types, including breast and prostate cancers. We conducted a study within the Breast and Prostate Cancer Cohort Consortium to examine the association between IL6 and PTGS2 polymorphisms and breast and prostate cancer risk. Twenty-seven polymorphisms, selected by pairwise tagging, were genotyped on 6292 breast cancer cases and 8135 matched controls and 8008 prostate cancer cases and 8604 matched controls. The large sample sizes and comprehensive single nucleotide polymorphism tagging in this study gave us excellent power to detect modest effects for common variants. After adjustment for multiple testing, none of the associations examined remained statistically significant at P = 0.01. In analyses not adjusted for multiple testing, one IL6 polymorphism (rs6949149) was marginally associated with breast cancer risk (TT versus GG, odds ratios (OR): 1.32; 99% confidence intervals (CI): 1.00-1.74, P-trend = 0.003) and two were marginally associated with prostate cancer risk (rs6969502-AA versus rs6969502-GG, OR: 0.87, 99% CI: 0.75-1.02; P-trend = 0.002 and rs7805828-AA versus rs7805828-GG, OR: 1.11, 99% CI: 0.99-1.26; P-trend = 0.007). An increase in breast cancer risk was observed for the PTGS2 polymorphism rs7550380 (TT versus GG, OR: 1.38, 99% CI: 1.04-1.83). No association was observed between PTGS2 polymorphisms and prostate cancer risk. In conclusion, common genetic variation in these two genes might play at best a limited role in breast and prostate cancers.

引用

页码：455 / 461

页数：7

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