Journal Article

Aurora-<i>A/STK15 T</i>+<i>91A</i> 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. Bowman, Gary L. Clayman, Scott M. Lippman, J. Jack Lee, Wei Zheng and Allan Balmain

in Carcinogenesis

Volume 26, issue 8, pages 1368-1373
Published in print August 2005 | ISSN: 0143-3334
Published online March 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi085
Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types

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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 <0.001) for cancer risk. These results confirm that the STK15 T+91A variant is a low penetrance cancer susceptibility allele affecting multiple cancer types, and provide genetic evidence from large-scale human population studies that genetic stability at the chromosome level is an important determinant of cancer susceptibility. The data also underline the advantages of comparative association studies involving study populations from different ethnic groups for determination of disease risk.

Keywords: CAMS, Chinese Academy of Medical Sciences; MDA, M.D. Anderson Cancer Center; PAR, population attributable risk; PHS, Physician's Health Study; SBCS, The Shanghai Breast Cancer Study; STK15T+91A, a low penetrance cancer susceptibility allele variant; SPS SEER, Seattle-Puget Sound Surveillance, Epidemiology and End Results Cancer Registry; UCI, University of California Irvine

Journal Article.  4634 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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