TY - JOUR
T1 - Pre-microRNA variants predict HPV16-positive tumors and survival in patients with squamous cell carcinoma of the oropharynx
AU - Guan, Xiaoxiang
AU - Sturgis, Erich M.
AU - Song, Xicheng
AU - Liu, Zhensheng
AU - El-Naggar, Adel K.
AU - Wei, Qingyi
AU - Li, Guojun
N1 - Funding Information:
UT MD Anderson Cancer Center Start-up Funds (to E.M.S.); N.I.H. Grant K-12 88084 (to E.M.S., faculty trainee; to R.C. Bast, P.I.); N.I.H. Grant R03 CA128110-01A1 (to E.M.S.), National Institute of Environmental Health Sciences Grant R01 ES011740 (to Q.W.); N.I.H. Grant R01 CA131274 (Q. Wei), N.I.H. Grant P-30 CA016672 (to The University of Texas M.D. Anderson Cancer Center); and N.I.H. Grants CA135679 (to G.L.) and CA133099 (to G.L.).
PY - 2013/4/28
Y1 - 2013/4/28
N2 - To identify non-tumor biomarkers for prediction of tumor HPV status and prognosis of patients with squamous cell carcinoma of the oropharynx (SCCOP), we evaluated the association of single nucleotide polymorphisms (SNPs) in pre-miRNAs with HPV16 status and survival for SCCOP patients. We analyzed HPV16 status in tumor specimens and genotyped four SNPs in pre-miRNAs (hsa-mir-146a rs2910164 G > C, hsa-mir-149 rs2292832 G > T, hsa-mir-196a2 rs11614913 C > T, and hsa-mir-499 rs3746444 A > G) in 309 SCCOP patients. Unconditional logistic regression models were used for calculation of odds ratio (OR) and 95% confidence intervals (CIs), and Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate associations. We found that statistically significant associations with HPV16-positive SCCOP and survival were found for hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913, while such similar associations were not observed for hsa-mir-149 rs2292832 and hsa-mir499 rs3746444. Compared with those with corresponding hsa-mir-146a CG/CC and has-mir-196a2 CC genotypes, the hsa-mir-146a GG and hsa-mir-196a2 CT/TT wild-type genotypes were significantly associated with HPV16-positive tumor status (adjusted OR, 2.4; 95% CI, 1.4-4.1 and adjusted OR, 2.1, 95% CI, 1.2-3.6), respectively. Patients having hsa-mir-146a rs2910164 GG and hsa-mir196a2 rs11614913 CT/TT genotypes had significantly better overall, disease-specific, and disease-free survival compared with those having the corresponding CG/CC and CC genotypes, respectively. Furthermore, these genotypes were significantly associated with reduced risk of overall death, death owing to disease, and recurrence after adjustment for important prognostic confounders including HPV status, smoking, and stage. Our findings indicate pre-miRNA polymorphisms may predict tumor HPV16-positive SCCOP cases and may be prognostic biomarkers for SCCOP.
AB - To identify non-tumor biomarkers for prediction of tumor HPV status and prognosis of patients with squamous cell carcinoma of the oropharynx (SCCOP), we evaluated the association of single nucleotide polymorphisms (SNPs) in pre-miRNAs with HPV16 status and survival for SCCOP patients. We analyzed HPV16 status in tumor specimens and genotyped four SNPs in pre-miRNAs (hsa-mir-146a rs2910164 G > C, hsa-mir-149 rs2292832 G > T, hsa-mir-196a2 rs11614913 C > T, and hsa-mir-499 rs3746444 A > G) in 309 SCCOP patients. Unconditional logistic regression models were used for calculation of odds ratio (OR) and 95% confidence intervals (CIs), and Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate associations. We found that statistically significant associations with HPV16-positive SCCOP and survival were found for hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913, while such similar associations were not observed for hsa-mir-149 rs2292832 and hsa-mir499 rs3746444. Compared with those with corresponding hsa-mir-146a CG/CC and has-mir-196a2 CC genotypes, the hsa-mir-146a GG and hsa-mir-196a2 CT/TT wild-type genotypes were significantly associated with HPV16-positive tumor status (adjusted OR, 2.4; 95% CI, 1.4-4.1 and adjusted OR, 2.1, 95% CI, 1.2-3.6), respectively. Patients having hsa-mir-146a rs2910164 GG and hsa-mir196a2 rs11614913 CT/TT genotypes had significantly better overall, disease-specific, and disease-free survival compared with those having the corresponding CG/CC and CC genotypes, respectively. Furthermore, these genotypes were significantly associated with reduced risk of overall death, death owing to disease, and recurrence after adjustment for important prognostic confounders including HPV status, smoking, and stage. Our findings indicate pre-miRNA polymorphisms may predict tumor HPV16-positive SCCOP cases and may be prognostic biomarkers for SCCOP.
KW - Genetic susceptibility
KW - MicroRNA polymorphisms
KW - Molecular epidemiology
KW - Oropharyngeal cancer
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84873076751&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873076751&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2012.11.048
DO - 10.1016/j.canlet.2012.11.048
M3 - Article
C2 - 23219900
AN - SCOPUS:84873076751
SN - 0304-3835
VL - 330
SP - 233
EP - 240
JO - Cancer Letters
JF - Cancer Letters
IS - 2
ER -