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Carcinogenesis Advance Access originally published online on July 22, 2004
Carcinogenesis 2004 25(11):2225-2230; doi:10.1093/carcin/bgh244
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Carcinogenesis vol.25 no.11 © Oxford University Press 2004; all rights reserved.

ARTICLE

Functional Phe31Ile polymorphism in Aurora A and risk of breast carcinoma

Tong Sun, Xiaoping Miao, Jinwei Wang1, Wen Tan, Yifeng Zhou, Chunyuan Yu and Dongxin Lin2

Department of Etiology and Carcinogenesis and 1 Department of Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

2 To whom correspondence should be addressed. Tel: +86 10 677 22460; Fax: +86 10 677 13359; Email: dlin{at}public.bta.net.cn

Aurora-A/BTAK/STK15, involved in regulating centrosomes and chromosome segregation, is overexpressed in human breast carcinoma and other cancers. The Phe31->Ile polymorphism in Aurora A alters the kinase function, with the Ile31 variant being preferentially amplified and associated with degree of aneuploidy in human tumors. We have previously shown that the Phe31Ile polymorphism is associated with the occurrence and advanced disease status of esophageal cancer. This case–control study examined the contribution of this polymorphism to susceptibility to development and progression of breast cancer. Aurora A genotypes were determined in 520 patients with breast carcinoma, 191 patients with benign breast diseases (BBD) and 520 controls. It was found that the Aurora A Ile/Ile genotype was significantly associated with increased risk of breast carcinoma occurrence [odds ratio (OR) 1.66; 95% confidence interval (95% CI) 1.29–2.12] compared with the Phe/Phe or Phe/Ile genotype. The increased risk for BBD and breast carcinoma related to the Ile/Ile genotype was more pronounced in younger subjects. Moreover, we found that patients carrying the Ile/Ile genotype tended to have ER–carcinomas (OR 2.56; 95% CI 1.24–5.26). No significant association was observed between the polymorphism and metastasis and disease stage of the cancer. These findings suggest that the Phe31Ile polymorphism in Aurora A may be a genetic modifier for developing breast carcinoma.


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