MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer.
Second primary tumor (SPT) and/or recurrence negatively impact the prognosis of patients with curatively treated early-stage head and neck cancer. MicroRNAs (miRNAs) play important roles in cancer development. We explored whether the variations of miRNA-related pathway were associated with the risk of SPT/recurrence in patients with early-stage head and neck cancer. This study includes 150 early-stage head and neck cancer patients with SPT/recurrence and 300 patients without SPT/recurrence. Two hundred and thirty-five tagging and potentially functional single-nucleotide polymorphisms (SNPs) were genotyped from eight miRNA biogenesis pathway genes and 135 miRNA-targeted genes. Eighteen miRNA-related SNPs were significantly associated with the risk of SPT/recurrence. The most significant SNP was rs3747238, a miRNA-binding site SNP in SMC1B. The variant homozygous genotype of this SNP was associated with a 1.74-fold increased risk [95% confidence interval (CI) 1.19-2.54; P = 0.004]. Cumulative effect analysis showed joint effects for the number of unfavorable genotype in patients. Survival tree analysis further identified the high-order gene-gene interactions and categorized the study subjects into low-, medium- and high-risk groups. Patients in the high-risk group had a 4.84-fold increased risk (95% CI: 3.11-7.51; P = 2.45 × 10(-12)) and a shorter event-free median survival time of 37.9 months (log rank P = 2.28 × 10(-13)). Our results suggested that miRNA-related genetic polymorphisms may be used individually and jointly to predict the risk of SPT/recurrence of early-stage head and neck cancer patients.
Zhang
Xiaofan
X
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yang
Hushan
H
Lee
J Jack
JJ
Kim
Edward
E
Lippman
Scott M
SM
Khuri
Fadlo R
FR
Spitz
Margaret R
MR
Lotan
Reuben
R
Hong
Waun K
WK
Wu
Xifeng
X
D018797:Cell Cycle Proteins / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D028884:Karyopherins / Q000235:genetics; D035683:MicroRNAs / Q000502:physiology*; D009364:Neoplasm Recurrence, Local / Q000209:etiology / Q000235:genetics*; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D000098550:Structural Maintenance of Chromosome Protein 1
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D028884:Karyopherins; D035683:MicroRNAs; C446511:XPO5 protein, human; D000098550:Structural Maintenance of Chromosome Protein 1
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