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Ovarian cancer risk associated with inherited inflammation-related variants.

Publication ,  Journal Article
White, KL; Schildkraut, JM; Palmieri, RT; Iversen, ES; Berchuck, A; Vierkant, RA; Rider, DN; Charbonneau, B; Cicek, MS; Sutphen, R; Birrer, MJ ...
Published in: Cancer Res
March 1, 2012

The importance of inflammation pathways to the development of many human cancers prompted us to examine the associations between single-nucleotide polymorphisms (SNP) in inflammation-related genes and risk of ovarian cancer. In a multisite case-control study, we genotyped SNPs in a large panel of inflammatory genes in 930 epithelial ovarian cancer cases and 1,037 controls using a custom array and analyzed by logistic regression. SNPs with P < 0.10 were evaluated among 3,143 cases and 2,102 controls from the Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI) post-GWAS collaboration. Combined analysis revealed association with SNPs rs17561 and rs4848300 in the interleukin gene IL1A which varied by histologic subtype (P(heterogeneity) = 0.03). For example, IL1A rs17561, which correlates with numerous inflammatory phenotypes, was associated with decreased risk of clear cell, mucinous, and endometrioid subtype, but not with the most common serous subtype. Genotype at rs1864414 in the arachidonate 5-lipoxygenase ALOX5 was also associated with decreased risk. Thus, inherited variation in IL1A and ALOX5 seems to affect ovarian cancer risk which, for IL1A, is limited to rarer subtypes. Given the importance of inflammation in tumorigenesis and growing evidence of subtype-specific features in ovarian cancer, functional investigations will be important to help clarify the importance of inherited variation related to inflammation in ovarian carcinogenesis.

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Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

March 1, 2012

Volume

72

Issue

5

Start / End Page

1064 / 1069

Location

United States

Related Subject Headings

  • Risk
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms, Glandular and Epithelial
  • Interleukin-1alpha
  • Inflammation
  • Humans
  • Genetic Predisposition to Disease
  • Female
 

Citation

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White, K. L., Schildkraut, J. M., Palmieri, R. T., Iversen, E. S., Berchuck, A., Vierkant, R. A., … Ovarian Cancer Association Consortium, . (2012). Ovarian cancer risk associated with inherited inflammation-related variants. Cancer Res, 72(5), 1064–1069. https://doi.org/10.1158/0008-5472.CAN-11-3512
White, Kristin L., Joellen M. Schildkraut, Rachel T. Palmieri, Edwin S. Iversen, Andrew Berchuck, Robert A. Vierkant, David N. Rider, et al. “Ovarian cancer risk associated with inherited inflammation-related variants.Cancer Res 72, no. 5 (March 1, 2012): 1064–69. https://doi.org/10.1158/0008-5472.CAN-11-3512.
White KL, Schildkraut JM, Palmieri RT, Iversen ES, Berchuck A, Vierkant RA, et al. Ovarian cancer risk associated with inherited inflammation-related variants. Cancer Res. 2012 Mar 1;72(5):1064–9.
White, Kristin L., et al. “Ovarian cancer risk associated with inherited inflammation-related variants.Cancer Res, vol. 72, no. 5, Mar. 2012, pp. 1064–69. Pubmed, doi:10.1158/0008-5472.CAN-11-3512.
White KL, Schildkraut JM, Palmieri RT, Iversen ES, Berchuck A, Vierkant RA, Rider DN, Charbonneau B, Cicek MS, Sutphen R, Birrer MJ, Pharoah PPD, Song H, Tyrer J, Gayther SA, Ramus SJ, Wentzensen N, Yang HP, Garcia-Closas M, Phelan CM, Cunningham JM, Fridley BL, Sellers TA, Goode EL, Ovarian Cancer Association Consortium. Ovarian cancer risk associated with inherited inflammation-related variants. Cancer Res. 2012 Mar 1;72(5):1064–1069.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

March 1, 2012

Volume

72

Issue

5

Start / End Page

1064 / 1069

Location

United States

Related Subject Headings

  • Risk
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms, Glandular and Epithelial
  • Interleukin-1alpha
  • Inflammation
  • Humans
  • Genetic Predisposition to Disease
  • Female