Association of miRNA-related genetic polymorphisms and prognosis in patients with esophageal squamous cell carcinoma.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is a deadly disease with a poor prognosis. The single nucleotide polymorphisms (SNPs) involved in microRNA (miRNA) functions are potential biomarkers for prognosis of various human cancers. We investigated the association of the miRNA-related SNPs with the prognosis of ESCC.


METHODS
A total of 504 patients with ESCC were enrolled. The genotypes of 18 miRNA-related SNPs were analyzed from the genomic DNA of peripheral leukocytes and were correlated with the prognosis of patients randomly assigned to a training set (n = 129) or an independent replication set (n = 375).


RESULTS
In the training group, only the rs4919510 SNP of the mir-608 gene was significantly associated with clinical outcome (CG vs. GG, hazard ratio [HR] 0.47, 95 % confidence interval [CI] 0.27-0.82, P = 0.008 for death, HR 0.47, 95 % CI 0.29-0.77, P = 0.002 for recurrence). The association for overall survival was confirmed in an independent replication group (CG vs. GG, HR 0.74, 95 % CI 0.56-0.97, P = 0.031 for death). Two other SNPs, rs14035 of RAN and rs7813 of GEMIN4, showed a borderline significant association with the prognosis of ESCC. In a combined analysis, we demonstrated the cumulative effect of the mir-608, RAN, and GEMIN4 polymorphisms on the clinical outcome of ESCC (HR 1.40, 95 % CI 1.18-1.67, P trend < 0.001 for mortality, HR 1.30, 95 % CI 1.10-1.53, P trend = 0.002 for recurrence). The cumulative effect was more evident in patients receiving concurrent chemoradiotherapy.


CONCLUSIONS
The hereditary genetic polymorphisms of mir-608, RAN, and GEMIN4 can serve as predictors for clinical outcome in ESCC patients treated with concurrent chemoradiotherapy.
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Pei-Wen
PW
Yang
Ya-Chuan
YC
Huang
Ching-Yueh
CY
Hsieh
Kuo-Tai
KT
Hua
Yu-Ting
YT
Huang
Tzu-Hsuan
TH
Chiang
Jin-Shing
JS
Chen
Pei-Ming
PM
Huang
Hsao-Hsun
HH
Hsu
Shuenn-Wen
SW
Kuo
Min-Liang
ML
Kuo
Jang-Ming
JM
Lee
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D016629:Esophagectomy; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics*; D015996:Survival Rate; D020931:ran GTP-Binding Protein / Q000235:genetics*
C406815:GEMIN4 protein, human; C000591804:MIRN608 microRNA, human; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; C120587:RAN protein, human; D017411:Ribonucleoproteins, Small Nuclear; D020931:ran GTP-Binding Protein