Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types

Amanda Ewart-Toland, Qi Dai, Yu-Tang Gao, Hiroki Nagase, Malcolm G Dunlop, Susan M Farrington, Rebecca A Barnetson, Hoda Anton-Culver, David Peel, Argyrios Ziogas, Dongxin Lin, Xiaoping Miao, Tong Sun, Elaine A Ostrander, Janet L Stanford, Mariela Langlois, June M Chan, Jinwei Yuan, Curtis C Harris, Elise D BowmanGary L Clayman, Scott M Lippman, J Jack Lee, Wei Zheng, Allan Balmain

Research output: Contribution to journalArticlepeer-review

Abstract

STK15 (Aurora-A) is a serine/threonine kinase involved in mitotic chromosomal segregation. A genetic variant in STK15 T+91A (resulting in the amino acid substitution F31I) is associated with increased aneuploidy in colon tumors and cell transformation in vitro. Since this polymorphism plays a role in mitotic control-a process critical for all cancer types-we conducted association analyses for risk of cancer development of the colon, breast, prostate, skin, lung and esophagus in 10 independent case-control populations. We carried out a meta-analysis of these 10 case-control studies together with 5 additional published studies for a total of 9549 cases of breast, colon, ovarian, prostate, lung, esophageal and non-melanoma skin cancer and 8326 population or hospital-based controls. Meta-analysis of three colorectal cancer studies showed an increased risk in T+91A homozygotes (OR=1.50; 95% CI of 1.14-1.99). Meta-analysis of four breast cancer studies showed increased risk for T+91A homozygotes (OR=1.35, 95% CI of 1.12-1.64). The results of the multiple cancer type meta-analysis for all 15 studies combined were significant for cancer risk in both homozygotes and heterozygotes. The T+91A heterozygotes show an OR of 1.10 (95% CI of 1.03-1.18, P-value=0.006) and the T+91A homozygotes show an OR of 1.40 (95% CI of 1.22-1.59, P-value
Original languageEnglish
Pages (from-to)1368-73
Number of pages6
JournalCarcinogenesis
Volume26
Issue number8
DOIs
Publication statusPublished - Aug 2005

Keywords

  • Animals
  • Breast Neoplasms
  • Case-Control Studies
  • Colonic Neoplasms
  • Esophageal Neoplasms
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Lung Neoplasms
  • Male
  • Mice
  • Prostatic Neoplasms
  • Protein-Serine-Threonine Kinases
  • Skin Neoplasms

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