TY - JOUR
T1 - Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients
AU - Reyes-Gibby, Cielito C.
AU - Wang, Jian
AU - Silvas, Mary Rose T.
AU - Yu, Robert K.
AU - Hanna, Ehab Y.
AU - Shete, Sanjay
N1 - Publisher Copyright:
© The Author(s) 2016.
PY - 2016/9/27
Y1 - 2016/9/27
N2 - Pain is often one of the first signs of squamous cell carcinoma of the head and neck (HNSCC). Pain at diagnosis is an important prognostic marker for the development of chronic pain, and importantly, for the overall survival time. To identify variants influencing severe pre-treatment pain in 1,368 patients newly diagnosed with HNSCC, we conducted a genome-wide association study based on 730,525 tagging SNPs. The patients were all previously untreated for cancer. About 15% of the patients had severe pre-treatment pain, defined as pain score ≥7 (0 = "no pain" and 10 = "worst pain"). We identified 3 common genetic variants in high linkage disequilibrium for severe pre-treatment pain, representing one genomic region at 1q44 (rs3862188, P = 3.45 × 10 â '8; rs880143, P = 3.45 × 10 â '8; and rs7526880, P = 4.92 × 10 â '8), which maps to the RP11-634B7.4 gene, a novel antisense gene to three olfactory receptor genes. Olfactory receptor genes, upstream effectors of the MAPK signaling cascade, might be novel target genes for pain in HNSCC patients. Future experimental validation to explore biological mechanisms will be key to defining the role of the intronic variants and non-coding RNA for pain in patients with HNSCC.
AB - Pain is often one of the first signs of squamous cell carcinoma of the head and neck (HNSCC). Pain at diagnosis is an important prognostic marker for the development of chronic pain, and importantly, for the overall survival time. To identify variants influencing severe pre-treatment pain in 1,368 patients newly diagnosed with HNSCC, we conducted a genome-wide association study based on 730,525 tagging SNPs. The patients were all previously untreated for cancer. About 15% of the patients had severe pre-treatment pain, defined as pain score ≥7 (0 = "no pain" and 10 = "worst pain"). We identified 3 common genetic variants in high linkage disequilibrium for severe pre-treatment pain, representing one genomic region at 1q44 (rs3862188, P = 3.45 × 10 â '8; rs880143, P = 3.45 × 10 â '8; and rs7526880, P = 4.92 × 10 â '8), which maps to the RP11-634B7.4 gene, a novel antisense gene to three olfactory receptor genes. Olfactory receptor genes, upstream effectors of the MAPK signaling cascade, might be novel target genes for pain in HNSCC patients. Future experimental validation to explore biological mechanisms will be key to defining the role of the intronic variants and non-coding RNA for pain in patients with HNSCC.
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U2 - 10.1038/srep34206
DO - 10.1038/srep34206
M3 - Article
C2 - 27670397
AN - SCOPUS:84989160136
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 34206
ER -