Genetic variants tied to head and neck cancer pain

A genome-wide association study has tied common genetic variants to pre-treatment pain, a finding with potential implications for precision medicine-based therapy decisions for patients with squamous cell carcinoma of the head and neck (HNSCC).Study findings were published in the Sept. 27 issue of Nature's Scientific Reports. The investigation was led by a multidisciplinary team including principal investigator Cielito Reyes-Gibby, Dr.PH., associate professor and research director of Emergency Medicine; co-principal investigator Sanjay Shete, Ph.D., professor of Biostatistics and Epidemiology; and co-investigator Ehab Hanna, M.D., professor of Head and Neck Surgery and medical director of the Head and Neck Center.

"We conducted this study because our previous studies have shown that pain at the time of diagnosis is an important prognostic marker for development of chronic pain, frequent visits to the emergency center, and overall survival time. Survival rates for patients with higher levels of pain are significantly shorter than for those with less severe pain," Reyes-Gibby said.

A review of 2,340 HNSCC patients revealed that oral cancer patients with severe pain had a 31 percent five-year survival rate versus 52 percent for those with less severe pain, Shete explained. Likewise, pharyngeal cancer patients with severe pain had a five-year survival rate of 33 percent versus 53 percent for those with less severe pain.

“In this genome-wide association study of pre-treatment pain, we identified variants influencing pain in 1,368 patients who were newly diagnosed with HNSCC and had not previously been treated for cancer," said Reyes-Gibby. "We found three common genetic variants linked to severe pre-treatment pain, which maps to a gene known as RP11-634B7.4.”

"Pain prior to treatment varies among patients with HNSCC when they present in the clinic. Pain level variability can be due to several factors such as site and stage of disease. The clinical implications of our findings are huge in the care of these patients, given that we can potentially intervene early by understanding their genetic makeup," Hanna said.

"Furthermore, substantial individual variability is observed in pain sensitivity and analgesic response," Reyes-Gibby added. "Adding to this complexity is the fact that opioids, the drug of choice for cancer pain, can be neurotoxic, with repeated dose escalation leading to increased tolerance."

The researchers believe that the finding may be important for precision medicine, which aims to consider each patient’s genetic, environmental, and lifestyle characteristics when developing and assigning treatment.

Other study team members include Jian Wang, Ph.D., assistant professor and Robert Yu, senior statistical analyst, both of Biostatistics.

The study was funded by the National Institutes of Health.