Functional Phe31Ile polymorphism in Aurora A and risk of breast carcinoma.
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.
Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Tong
T
Sun
Xiaoping
X
Miao
Jinwei
J
Wang
Wen
W
Tan
Yifeng
Y
Zhou
Chunyuan
C
Yu
Dongxin
D
Lin
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007532:Isoleucine; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016017:Odds Ratio; D010649:Phenylalanine; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
D007532:Isoleucine; D010649:Phenylalanine; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases