Mature microRNA sequence polymorphism in MIR196A2 is associated with risk and prognosis of head and neck cancer.
OBJECTIVE
The central role of microRNAs as regulators of translation has been well established, whereas the relationships between genetic variation in microRNAs and disease risk is only beginning to be explored. A polymorphism in the MIR196A2 locus has shown associations with lung, breast, esophageal, and gastric tumors but has not been examined in head and neck cancers, which share similar pathology and etiology to these diseases.


METHODS
We studied a polymorphism in the mature sequence of MIR196A2 (rs11614913, C/T) in a population-based case-control study (n = 1,039) of head and neck squamous cell carcinoma (HNSCC) to determine if MIR196A2 genotype was associated with disease occurrence and patient survival.


RESULTS
Presence of any variant allele was associated with a significantly reduced risk for HNSCC (odds ratio, 0.8; 95% confidence interval, 0.56-0.99). Homozygous variant allele carriers with pharyngeal tumors had significantly reduced survival compared with wild-type and heterozygous cases (hazard ratio, 7.4; 95% confidence interval, 1.9-28.2). Expression analysis in a subset of tumors (n = 83) revealed no significant difference in relative expression of either miR-196a or miR-196a* by MIR196A2 genotype.


CONCLUSIONS
These data demonstrate a role for MIR196A2 genotype in susceptibility and prognosis of HNSCC.
Christensen
Brock C
BC
Department of Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, Rhode Island 02903, USA.
Avissar-Whiting
Michele
M
Ouellet
Lauren G
LG
Butler
Rondi A
RA
Nelson
Heather H
HH
McClean
Michael D
MD
Marsit
Carmen J
CJ
Kelsey
Karl T
KT
D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
C542543:MIRN196 microRNA, human; D035683:MicroRNAs