A cancer diagnosis hits hard.  Despite the stress, patients must learn about their treatment options to have fully informed discussions with an oncologist and other specialists on treatment decisions. If your treatment plan includes surgery to remove a tumor, there are a few things you should know to help ensure success.  The surgeon’s skill and experience are certainly important factors, but the type of anesthesia used can impact the risk of cancer recurrence.  Adequate pain control can also affect your recovery and the risk of permanent disability.  As well, effective nausea management will have a significant impact on your quality of life.

This article discusses how pharmacogenetic testing before surgery can assist your doctors in optimizing your treatment and maximizing the chances of your full recovery.

Anesthesia:

Recent studies have shown that the type of anesthesia used during surgery can affect the risk of cancer metastasis and long-term survival in patients with cancer.  Intravenous anesthesia with propofol was shown in one study to have a five-year patient survival rate, almost 1.5 times greater than that for patients given inhaled anesthetics.  Inhalational anesthetics suppress immune response and may increase the risk of metastasis.  Propofol does not suppress immune response and has anti-inflammatory and antioxidant properties, both of which are beneficial for cancer patients.

A pharmacogenetic test can help your anesthesiologist determine the clinically effective propofol dose for you.  Propofol metabolism and clearance is controlled by an enzyme in your liver, the CYP2B6 enzyme.  Up to 50% of people in North America have inherently reduced function of this enzyme and have a slower propofol elimination rate, prolonging recovery from anesthesia and increasing the risk of propofol-induced side effects such as numbness and confusion.  Elderly patients with a reduced function of this enzyme may benefit from a lower propofol dose to facilitate recovery.

Nausea management:

Recovery from anesthesia frequently causes severe nausea during the post-operative period.  Intravenous administration of fluids helps to clear the remaining anesthetic drug from your bloodstream and reduce nausea symptoms.  However, some patients need additional anti-nausea medications such as dolasetron, ondansetron, palonosetron, or tropisetron.  People who are Ultrarapid CYP2D6 metabolizers (the enzyme that controls the clearance of these drugs), clear these four anti-nausea drugs too fast and do not get relief from them.  Pharmacogenetic test results may recommend alternative drugs not predominantly metabolized by CYP2D6 (for example, granisetron).

A pharmacogenetic test prior to surgery can help your anesthesiologist select appropriate medication to manage your nausea.

Pain control:

To control pain during surgery, fast-acting injected opioids such as remifentanil, fentanyl, and morphine are commonly used.  Potent opioids are needed to control pain in the post-surgery period as well.  Some people want to “tough through” the pain due to the fear of developing opioid dependence and refuse to take opioids or intentionally reduce the drug dose.  However, multiple studies have shown that poor pain control before, during, and after surgery greatly increases the risk of developing chronic pain.  Chronic pain has a significant impact not only on quality of life for many years but also reduces the survival rate for cancer patients.  When your body is under constant stress triggered by pain, high levels of stress hormones like cortisol suppress your immune system and increase the risk of cancer recurrence.  Hence, adequate pain control in the first 2-3 days after the surgery is very important for long term survival and quality of life.  Patients who take opioids to control high levels of pain do not become addicted if the opioids are reduced or stopped entirely a few days after the surgery.  However, patients discharged home with high opioid doses are at a much greater risk of developing opioid dependence. Long term use of opioids also reduces their effectiveness due to tolerance development and increased sensitivity to pain – a phenomenon called opioid-induced hyperalgesia.  Therefore, it is prudent to control pain effectively right after the surgery.

Some patients have a reduced response to opioids due to inherited variations in the OPRM1 gene, which controls how your body processes them.  Multiple studies have shown that people with OPRM1 variants require higher doses to achieve adequate pain relief when compared to people who do not carry such variations.

Furthermore, when patients are discharged from the recovery room to a regular bed, they are switched to oral opioids such as tramadol, hydrocodone, or oxycodone.  These require activation by a liver enzyme called CYP2D6 to become effective.  Patients who cannot process these medications should avoid them altogether (see CPIC pharmacogenetic prescribing information).  Patients who are Poor CYP2D6 metabolizers could be treated with high doses of drugs like Advil and similar NSAID medications, or morphine if stronger pain relief is needed.  People who process oral opioids more slowly due to reduced liver enzyme activity (between 12 and 20% of the population) may require higher tramadol or oxycodone doses to compensate for slower drug activation.

Additionally, 5-10% of people are ultrarapid metabolizers of oral opioids.  They convert tramadol, codeine, and oxycodone too fast, leading to nausea and delirium.  They are even at risk for serious breathing issues at higher doses.  Ultrarapid metabolizers experience shorter pain relief at standard doses and are at an elevated risk of addiction with continued use of these opioids.  Ultrarapid metabolizers can also benefit from NSAIDs or morphine for pain control in the post-surgery period.

Pillcheck tests for CYP2D6 and OPRM1 function and can help your doctors optimize your pain management and select appropriate pain relief therapy.  But once again, remember to have your test done several weeks in advance of your surgery so you’ll be able to show your results to your doctor and anesthesiologist.

Chemotherapy:

If chemotherapy is scheduled after the surgery, a pharmacogenetic test for TPMT and DYPD (aka DPD) genes can also help to identify the appropriate dose and type of chemotherapy.  CPIC guidelines for DPYD and Fluoropyrimidines and for TPMT, NUDT15 and Thiopurines can assist oncologists in the selection and dosing of chemotherapy drugs used for treatment of breast, colon, and other types of cancer.  You can read more about the role of these genes in chemotherapy here.

For women treated with tamoxifen, Pillcheck can help to identify whether higher tamoxifen dose or alternative treatment is warranted to prevent cancer recurrence.  Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy (January 2018) recommends dose increase for women with reduced CYP2D6 function, while a switch to aromatase inhibitors is needed for women with absent CYP2D6 function.  Pillcheck can also identify whether the use of tamoxifen poses a higher risk of thrombosis and stroke for women carrying mutations in F2 or F5 genes as per the FDA drug warning label.

Conclusion

Broad pharmacogenetic tests such as Pillcheck can be a vital tool to help you and your doctors navigate medication decisions for your cancer surgery, pain, and nausea management.  Order Pillcheck today to get your results before the planned cancer surgery to maximize the success of your treatment.

The key points to remember:

1. Pain management is extremely important after cancer surgery.  People whose cancer pain is not well-controlled run a higher risk of developing chronic pain.  Studies have shown that effective pain management can make a difference in cancer survival rates.
2. Effective anti-nausea management makes a big difference in patient comfort after surgery and during chemotherapy treatment if you require it.
3. Pharmacogenetics can guide the choice of chemotherapy agents and dose to reduce the risk of toxicity.

Perry NJS, et al., Can Anesthesia Influence Cancer Outcomes After Surgery? JAMA Surg. 2019;154(4):279-280. doi:10.1001/jamasurg.2018.4619

Eugene AR CYP2B6 Genotype Guided Dosing of Propofol Anesthesia in the Elderly based on Nonparametric Population Pharmacokinetic Modeling and Simulations. Int J Clin Pharmacol Toxicol. 2017;6(1):242-249.

Crews KR., et al., Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update CLINICAL PHARMACOLOGY & THERAPEUTICS 2014; 95(4): 376-382

Hwang IC., et al., OPRM1 A118G Gene Variant and Postoperative Opioid Requirement: A Systematic Review and Meta-analysis Anesthesiology 2014;121:825-834

Bell GC, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron CLINICAL PHARMACOLOGY & THERAPEUTICS 2017; 102(2):213-218

Gaedigk A, et al., Prediction of CYP2D6 phenotype from genotype across world populations Genet Med. 2017 Jan; 19(1): 69–76.