The Genetic Connection

In addition to genetic polymorphisms associated with the experience of pain, several SNPs have been linked to responses to pain analgesia, such as with opioid therapy. Although opioids are often an efficacious therapy for pain related to cancer, patients may show varying responses to opioid treatment in association with SNPs in OPRM1, COMT, ABCB1 and other genes.1,3 OPRM1, which encodes an opioid receptor, and COMT are genes linked to neurotransmission pathways, and the effects of SNPs in these genes may relate to opioid requirements.1

The metabolism and transport of opioids can also be factors in patients’ responses to them.1 Genetic variations that result in differences in the activity of enzymes used for drug metabolism, such as cytochrome P450 enzymes, are thought to impact efficacy and drug clearance.1,3 Genetic variation has additionally been associated with responses to some nonopioid analgesics.3

Adverse effects with opioids, such as nausea and vomiting, also may be associated with SNPs.7 In a recent study, a SNP in the PDE3A gene appeared to show a relationship between opioid analgesia and nausea and vomiting.7 This connection seemed to not be strong, however.7 Another study has reported possible links between SNPs and hepatotoxicity with acetaminophen, a nonopioid analgesic.8

Multiple studies have pointed to possible genetic biomarkers for pain, but conflicting results have also been found, suggesting that factors beyond genetic variation may be involved in pain and opioid response.1,9 While SNPs for some genes, such as COMT and OPRM1, have shown firmer evidence of having roles in cancer pain, many other apparent genetic biomarkers for pain require further evaluation.1


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Additionally, expression of a gene, such as OPRM1, can be influenced by epigenetic factors, with possible consequences for opioid tolerance, a phenomenon that may be missed in an analysis of SNPs.10

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Conclusion

Despite these complexities, the role of genetic variation as a factor in the experience of pain is becoming clearer.9 Currently identified genetic polymorphisms may not account for all aspects of cancer pain and responses to analgesia, and guidance with using SNP results is not yet clear.1 However, the use of genetic biomarkers related to pain and analgesic response has the potential to become incorporated into strategies to optimize pain management in patients with cancer pain or pain associated with cancer treatment.1

Because nurses in clinical practice are often involved in pain management, competency in assessing and utilizing genetic biomarkers may become an increasingly useful tool for nurses in managing pain related to cancer and cancer treatment.1

References

  1. Yang GS, Barnes NM, Lyon DE, Dorsey SG. Genetic variants associated with cancer pain and response to opioid analgesics: implications for precision pain management. Semin Oncol Nurs. 2019;35(3):291-299.
  2. Schatz AA, Oliver TK, Swarm RA, et al. Bridging the gap among clinical practice guidelines for pain management in cancer and sickle cell disease. J Natl Compr Canc Netw. 2020;18(4):392-399.
  3. Subramaniam AV, Yehya AHS, Oon CE. Molecular basis of cancer pain management: an updated review. Medicina (Kaunas). 2019;55(9):584.
  4. Garcia-Giralt N, Rodriguez-Sanz M, Prieto-Alhambra D, et al. Genetic determinants of aromatase inhibitor-related arthralgia: the B-ABLE cohort study. Breast Cancer Res Treat. 2013;140(2):385-395.
  5. Lintermans A, Van Asten K, Jongen L, et al. Genetic variant in the osteoprotegerin gene is associated with aromatase inhibitor-related musculoskeletal toxicity in breast cancer patients. Eur J Cancer. 2016;56:31-36.
  6. Liu J, Tang X, Shi F, et al. Genetic polymorphism contributes to 131I radiotherapy-induced toxicities in patients with differentiated thyroid cancer. Pharmacogenomics. 2018;19(17):1335-1344.
  7. Colombo F, Pintarelli G, Galvan A, et al. Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients. Sci Rep. 2020;10(1):542.
  8. Heruth DP, Shortt K, Zhang N, Li DY, Zhang LQ, Qing Ye S. Genetic association of single nucleotide polymorphisms with acetaminophen-induced hepatotoxicity. J Pharmacol Exp Ther. 2018;367(1):95-100.
  9. Zorina-Lichtenwalter K, Meloto CB, Khoury S, Diatchenko L. Genetic predictors of human chronic pain conditions. Neuroscience. 2016;338:36-62.
  10. Viet CT, Dang D, Aouizerat BE, et al. OPRM1 methylation contributes to opioid tolerance in cancer patients. J Pain. 2017;18(9):1046-1059.

This article originally appeared on Oncology Nurse Advisor