Genetics may influence susceptibility to and severity of pain in cancer patients

TAMPA, Fla.-Genotyping could become a pivotal part of an individualized treatment program for cancer patients because some patients seem more susceptible to pain than others, according to research presented at the 2009 American Society of Preventive Oncology meeting.

"If we know that certain patients are at a higher risk for severe pain, or any other cancer-related symptoms, by looking at their genetic make-up, then we can intervene much earlier and hopefully improve our ability to help them," said Cielito Reyes-Gibby, DrPH, assistant professor in the department of epidemiology at M.D. Anderson Cancer Center in Houston.

In a study of 677 patients with newly diagnosed non-small-cell lung cancer, 16% of the patients reported severe pain. However, the risk of severe pain was lowered by as much as 70% in those patients who possessed certain genes.

"Chronic inflammation is a tumor promoter, resulting in aggressive cancerous growth and spread. It is thought that many of the same inflammatory factors that promote tumor growth are also pain modulators," Dr. Reyes-Gibby explained. "Single nucleotide polymorphisms, or SNPs, in the inflammation genes have been shown to alter their expressions or functions, and thus may be associated with an altered risk for pain severity." Dr. Reyes-Gibby's earlier research showed that polymorphisms in interleukin-6, tumor necrosis factor–alpha, and interleukin-8 influenced pain severity in patients with newly diagnosed lung cancer. "But pain is complex and it is likely that multiple genes influence one's vulnerability to pain. Assessing polymorphisms in several genes that interact in the same pathway might provide more robust results," she said (ASCO 2008 abstract 9503).

In the latest study, she looked at a comprehensive panel of 59 SNPs in 37 inflammation genes in non-Hispanic, Caucasian patients with newly diagnosed lung cancer and assessed their association with pain severity, taking into account the influence of clinical and demographic factors on pain severity in this population.

The patients filled out a questionnaire that asked them about pain, depressed mood, and fatigue. Blood samples were drawn and DNA extracted and genotyped (see Table).

In all, 106 patients reported that they had severe pain. Interestingly, germline variants in genes including TNF-beta, PTGS2 (also known as COX2), interleukin 2, and NF Kappa B were found to be significantly associated with pain severity. Patients carrying variant genotypes for these genes had their risk for severe pain reduced by as much as 50%.

The germline variants we assessed in this study are functional. For example, "the PTGS2 gene encodes the proinflammatory cyclooxygenase (COX2) enzyme, and the particular SNP we found-the Exon 10+837T>C of the PTSG2 gene-modulates expression of COX2," Dr. Reyes-Gibby explained. "Indeed, COX2 is a therapeutic target for pain. Inhibition of COX2 enzymatic activities is responsible for the anti-inflammatory properties of aspirin, indomethacin, ibuprofen, and related NSAIDs such as rofecoxib (Vioxx) and celecoxib (Celebrex)."

"It is important to note, however, that these are preliminary findings and so we need to conduct additional studies for validation purposes," Dr. Reyes-Gibby said