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Carcinogenesis Advance Access published online on August 21, 2006
Carcinogenesis, doi:10.1093/carcin/bgl149
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received March 20, 2006
Revised July 28, 2006
Accepted August 4, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Polymorphisms of STK15 (Aurora-A) gene and lung cancer risk in Caucasians

Jian Gu 1, Yubo Gong 1, Maosheng Huang 1, Charles Lu 2, Margaret R. Spitz 1, and Xifeng Wu 1 *

1 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
2 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030

* To whom correspondence should be addressed.
Xifeng Wu, E-mail: xwu{at}mdanderson.org


  Abstract

STK15/Aurora A is a centrosome-localized serine/threonine kinase that functions primarily in centrosome maturation and mitotic spindle assembly. In a large lung cancer case-control study of 1401 cases and 1397 controls including three ethnic groups, we examined the associations between two non-synonymous SNPs (Phe31Ile and Val57Ile) of the STK15 gene and lung cancer risk. There were statistically significant differences in the distribution of the genotypes (P < 0.0001) and haplotypes (P < 0.0001) by ethnicity for the Phe31Ile, but not the Val57Ile variant. Caucasians with the homozygous variant Phe31Ile genotype (Ile/Ile) were at a significantly reduced risk for lung cancer (OR=0.63, 95% CI = 0.41-0.96). The variant allele of Val57Ile was not associated with lung cancer risk overall. However, men with the homozygous variant genotype (Ile/Ile) had a reduced lung cancer risk as compared with men with the wild type genotype (Val/Val) (OR = 0.42, 95% CI = 0.19-0.94). When we performed joint analysis of these two polymorphisms, compared to the reference group (TT + GG, 40.99% of controls), homozygous Ile31 allele/wild type Val57 allele (AA + GG) carriers (5.45% of controls) exhibited a reduced lung cancer risk (OR = 0.78, 95% CI = 0.63 - 0.97). This is the first epidemiological study to report significant associations between STK15 polymorphisms and lung cancer risk.

Keywords: centrosome; STK15; SNP; lung cancer.
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