Genetic Polymorphisms and Pain

Genetic Polymorphisms: Understanding Their Relationship With Cancer Pain – Clinical Pain Advisor – by Vicki Moore, PhD – June 2020

Cancer pain is no different than any other pain and this article explains why and how genetic factors are critical in determining opioid doses.

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.  

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.

The metabolism and transport of opioids can also be factors in patients’ responses to them.

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.

Genetic variation has additionally been associated with responses to some nonopioid analgesics.

…and many other medications of all kinds. What is true for opioid medication is equally true for other drugs.

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.

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.


Despite these complexities, the role of genetic variation as a factor in the experience of pain is becoming clearer.

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. 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.

This is excellent information to counter any kind of standardization of opioids doses, so I’ve included the articles that were referenced. It’s clear that this issue has been known for years, so there’s no excuse for any doctor to abide by or hold such unscientific opinions.

Below are 10 additional references to support this article:


  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.


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