Risk of Ovarian Cancer and the NF-κB Pathway: Genetic Association with IL1A and TNFSF10

被引：43

作者：

Charbonneau, Bridget ^{[1
]}

Block, Matthew S. ^{[2
]}

Bamlet, William R. ^{[3
]}

Vierkant, Robert A. ^{[3
]}

Kalli, Kimberly R. ^{[2
]}

Fogarty, Zachary ^{[3
]}

Rider, David N. ^{[3
]}

Sellers, Thomas A. ^{[6
]}

Tworoger, Shelley S. ^{[7
,9
]}

Poole, Elizabeth ^{[7
,9
]}

Risch, Harvey A. ^{[10
]}

Salvesen, Helga B. ^{[11
,12
]}

Kiemeney, Lambertus A. ^{[14
,15
,17
]}

Baglietto, Laura ^{[18
,19
]}

Giles, Graham G. ^{[18
,19
,22
]}

Severi, Gianluca ^{[18
,19
]}

Trabert, Britton ^{[25
]}

Wentzensen, Nicolas ^{[25
]}

Chenevix-Trench, Georgia ^{[24
]}

Whittemore, Alice S. ^{[26
]}

Sieh, Weiva ^{[26
]}

Chang-Claude, Jenny ^{[32
]}

Bandera, Elisa V. ^{[41
]}

Orlow, Irene ^{[42
]}

Terry, Kathryn ^{[8
,9
]}

Goodman, Marc T. ^{[27
]}

Thompson, Pamela J. ^{[27
]}

Cook, Linda S. ^{[45
]}

Rossing, Mary Anne ^{[46
,47
]}

Ness, Roberta B. ^{[48
]}

Narod, Steven A. ^{[52
]}

Kupryjanczyk, Jolanta ^{[58
]}

Lu, Karen ^{[49
]}

Butzow, Ralf ^{[62
,63
]}

Doerk, Thilo ^{[33
]}

Pejovic, Tanja ^{[64
,65
]}

Campbell, Ian ^{[20
,21
,23
]}

Le, Nhu D. ^{[53
]}

Bunker, Clareann H. ^{[66
]}

Bogdanova, Natalia ^{[33
]}

Runnebaum, Ingo B. ^{[34
]}

Eccles, Diana ^{[70
]}

Paul, James ^{[71
]}

Wu, Anna H. ^{[29
]}

Gayther, Simon A. ^{[29
]}

Hogdall, Estrid ^{[82
,83
]}

Heitz, Florian ^{[35
,37
]}

Kaye, Stanley B. ^{[72
]}

Karlan, Beth Y. ^{[28
]}

Anton-Culver, Hoda ^{[31
]}

机构：

[1] Mayo Clin Rochester, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN 55905 USA

[2] Mayo Clin Rochester, Dept Med Oncol, Rochester, MN 55905 USA

[3] Mayo Clin Rochester, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA

[4] Mayo Clin, Dept Hlth Sci Res, Dept Immunol, Rochester, MN 55905 USA

[5] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN 55905 USA

[6] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Div Populat Sci, Tampa, FL 33682 USA

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

[8] Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA

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

[10] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA

[11] Univ Bergen, Dept Clin Sci, Bergen, Norway

[12] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway

[13] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway

[14] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands

[15] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands

[16] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, NL-6525 ED Nijmegen, Netherlands

[17] Comprehens Canc Ctr Netherlands, Utrecht, Netherlands

[18] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

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

[20] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia

[21] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[22] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia

[23] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic, Australia

[24] Queensland Inst Med Res, Canc Div, Herston, Qld 4006, Australia

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

[26] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Palo Alto, CA 94304 USA

[27] Samuel Oschin Comprehens Canc Inst, Los Angeles, CA USA

[28] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA

[29] Univ Southern Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA

[30] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

[31] Univ Calif Irvine, Sch Med, Dept Epidemiol, Ctr Canc Genet Res & Prevent, Irvine, CA 92717 USA

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

[33] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany

[34] Univ Jena, Jena Univ Hosp, Dept Gynecol, Jena, Germany

[35] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany

[36] Inst Humangenet Wiesbaden, Wiesbaden, Germany

[37] Kliniken Essen Mitte, Evang Huyssens Stiftung, Knappschaft GmbH, Dept Gynecol & Gynecol Oncol, Essen, Germany

[38] Univ Hosp Erlangen, Ctr Comprehens Canc, Dept Gynecol & Obstet, Erlangen, Germany

[39] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany

[40] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany

[41] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA

[42] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[43] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA

[44] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA

[45] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA

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

[47] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[48] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA

[49] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA

[50] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

来源：

CANCER RESEARCH | 2014年 / 74卷 / 03期

基金：

加拿大健康研究院; 英国医学研究理事会; 英国惠康基金;

关键词：

NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SINGLE-NUCLEOTIDE POLYMORPHISMS; PELVIC-INFLAMMATORY-DISEASE; REPRODUCTIVE FACTORS; ACTIVATION; INTERLEUKIN-1; APOPTOSIS; ESTROGEN; ENDOMETRIOSIS; METAANALYSIS;

D O I：

10.1158/0008-5472.CAN-13-1051

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1 alpha (IL1A) is both regulated by and able to activate NF-kappa B, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-kB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P = 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 x 10(-5), only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted.

引用

页码：852 / 861

页数：10

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