Skip to main content

Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10.

Publication ,  Journal Article
Charbonneau, B; Block, MS; Bamlet, WR; Vierkant, RA; Kalli, KR; Fogarty, Z; Rider, DN; Sellers, TA; Tworoger, SS; Poole, E; Risch, HA; Sieh, W ...
Published in: Cancer Res
February 1, 2014

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-1α (IL1A) is both regulated by and able to activate NF-κB, 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-κB 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 × 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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

February 1, 2014

Volume

74

Issue

3

Start / End Page

852 / 861

Location

United States

Related Subject Headings

  • TNF-Related Apoptosis-Inducing Ligand
  • Signal Transduction
  • Risk
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Interleukin-1alpha
  • Humans
  • Genetic Association Studies
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Charbonneau, B., Block, M. S., Bamlet, W. R., Vierkant, R. A., Kalli, K. R., Fogarty, Z., … Goode, E. L. (2014). Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10. Cancer Res, 74(3), 852–861. https://doi.org/10.1158/0008-5472.CAN-13-1051
Charbonneau, Bridget, Matthew S. Block, William R. Bamlet, Robert A. Vierkant, Kimberly R. Kalli, Zachary Fogarty, David N. Rider, et al. “Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10.Cancer Res 74, no. 3 (February 1, 2014): 852–61. https://doi.org/10.1158/0008-5472.CAN-13-1051.
Charbonneau B, Block MS, Bamlet WR, Vierkant RA, Kalli KR, Fogarty Z, et al. Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10. Cancer Res. 2014 Feb 1;74(3):852–61.
Charbonneau, Bridget, et al. “Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10.Cancer Res, vol. 74, no. 3, Feb. 2014, pp. 852–61. Pubmed, doi:10.1158/0008-5472.CAN-13-1051.
Charbonneau B, Block MS, Bamlet WR, Vierkant RA, Kalli KR, Fogarty Z, Rider DN, Sellers TA, Tworoger SS, Poole E, Risch HA, Salvesen HB, Kiemeney LA, Baglietto L, Giles GG, Severi G, Trabert B, Wentzensen N, Chenevix-Trench G, for AOCS/ACS group, Whittemore AS, Sieh W, Chang-Claude J, Bandera EV, Orlow I, Terry K, Goodman MT, Thompson PJ, Cook LS, Rossing MA, Ness RB, Narod SA, Kupryjanczyk J, Lu K, Butzow R, Dörk T, Pejovic T, Campbell I, Le ND, Bunker CH, Bogdanova N, Runnebaum IB, Eccles D, Paul J, Wu AH, Gayther SA, Hogdall E, Heitz F, Kaye SB, Karlan BY, Anton-Culver H, Gronwald J, Hogdall CK, Lambrechts D, Fasching PA, Menon U, Schildkraut J, Pearce CL, Levine DA, Kjaer SK, Cramer D, Flanagan JM, Phelan CM, Brown R, Massuger LFAG, Song H, Doherty JA, Krakstad C, Liang D, Odunsi K, Berchuck A, Jensen A, Lubinski J, Nevanlinna H, Bean YT, Lurie G, Ziogas A, Walsh C, Despierre E, Brinton L, Hein A, Rudolph A, Dansonka-Mieszkowska A, Olson SH, Harter P, Tyrer J, Vitonis AF, Brooks-Wilson A, Aben KK, Pike MC, Ramus SJ, Wik E, Cybulski C, Lin J, Sucheston L, Edwards R, McGuire V, Lester J, du Bois A, Lundvall L, Wang-Gohrke S, Szafron LM, Lambrechts S, Yang H, Beckmann MW, Pelttari LM, Van Altena AM, van den Berg D, Halle MK, Gentry-Maharaj A, Schwaab I, Chandran U, Menkiszak J, Ekici AB, Wilkens LR, Leminen A, Modugno F, Friel G, Rothstein JH, Vergote I, Garcia-Closas M, Hildebrandt MAT, Sobiczewski P, Kelemen LE, Pharoah PDP, Moysich K, Knutson KL, Cunningham JM, Fridley BL, Goode EL. Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10. Cancer Res. 2014 Feb 1;74(3):852–861.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

February 1, 2014

Volume

74

Issue

3

Start / End Page

852 / 861

Location

United States

Related Subject Headings

  • TNF-Related Apoptosis-Inducing Ligand
  • Signal Transduction
  • Risk
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Interleukin-1alpha
  • Humans
  • Genetic Association Studies