Association of Aurora-A (STK15) kinase polymorphisms with clinical outcome of esophageal cancer treated with preoperative chemoradiation.
BACKGROUND
Aurora-A/STK15 is a serine/threonine kinase critical for regulated chromosome segregation and cytokinesis. We investigated the association between 2 nonsynonymous single nucleotide polymorphisms in the coding region of STK15, T91A (Phe31Ile) and G169A (Val57Ile), and clinical outcome of esophageal cancer treated with preoperative chemoradiation.


METHODS
Genotypes at Phe31Ile and Val57Ile were assessed from peripheral blood lymphocytes of 190 esophageal cancer patients and were correlated to response to treatment, recurrence rate, risk of death, disease-free survival (DFS) and median survival time (MTS).


RESULTS
All patients had resectable esophageal or gastroesophageal junction cancer and received preoperative chemoradiation followed by esophagectomy. The heterozygous variant Phe31/Ile variant was significantly associated with tumor recurrence (odds ratio [OR] = 4.39; 95% confidence interval [CI], 2.12-8.94; P < .001), shorter DFS (P = .0001), and shorter MTS (P = .012). For patients receiving cisplatin-based therapy, only the variant Phe31/Ile had an adverse effect on response (OR = 2.8; 95% CI, 1.01-5.17; P = .048) and MTS (P = .026). The variant 91A-169G haplotype carried a significant risk for lack of complete response (OR = 2.54; 95% CI, 1.15-5.54) and higher rate of recurrence (OR = 2.73; 95%CI, 1.00-7.29). The presence of at least 1 variant allele at each locus further increased the risk of recurrence (adjusted OR = 6.21; 95% CI, 2.28-17.11; P = <.001), and was associated significantly shorter DFS (P = .003).


CONCLUSIONS
Our study shows that functional SNPs in the STK15 gene are associated with higher rate of recurrence, higher likelihood of chemoratiotherapy-resistance, shorter DFS, and shorter MTS. Confirmation of our data and understanding the mechanisms through which STK15 functional SNPs mediate resistance to chemoradiotherapy are warranted.
Department of Experimental Therapeutics, The University of MD Anderson Cancer Center, Houston, Texas 77030, USA.
Jennifer Y
JY
Pan
Jaffer A
JA
Ajani
Jian
J
Gu
Yubo
Y
Gong
Angel
A
Qin
Angel
A
Quin
Maosheng
M
Hung
Xifeng
X
Wu
Julie G
JG
Izzo
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D064096:Aurora Kinase A; D064127:Aurora Kinases; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012008:Recurrence; D016896:Treatment Outcome
C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin; D005472:Fluorouracil