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Morphine and Metastasis pp 95–112Cite as

Genetic Polymorphisms in the µ-Opioid Receptor Gene and Breast Cancer Survival

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Abstract

Preclinical studies suggest that endogenous opioids and/or opioid medications may contribute to tumor growth. However, endogenous and exogenous opioids have not been modulated over time in cancer patients, who often need opioids for pain control. Most of the analgesic effect of opioids occurs through the activation of the μ-opioid receptor. The most common naturally occurring genetic variation of this receptor in humans is the so-called A118G mutation. Individuals with this mutation have been shown to have a reduced analgesic response to opioid medications. In a recent study, we used this naturally occurring genetic variation to look for evidence that endogenous and/or exogenous opioids influence tumor growth in humans. We hypothesized that if opioids do influence tumor growth, then cancer patients with the A118G mutation, as a group, should have longer survivals than those without it. Using data from the Carolina Breast Cancer Study, we found that, among 2,039 women diagnosed with breast cancer, the presence of A118G was associated with longer breast cancer specific survival. The protective effect of A118G was limited to invasive cases only and appeared to increase with the stage of cancer at diagnosis. This study did not assess whether opioid pain medications have any influence on cancer mortality. Moreover, the study was performed in African Americans and European Americans only, and requires replication.

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Abbreviations

DAMGO:

[D-Ala2, N-MePhe4, Gly-ol]-enkephalin

OPRM1 :

μ-opioid receptor gene 1

cAMP:

adenosine 3′ 5′-cyclic monophosphate

ER:

estrogen receptor

kb:

kilobases

mRNA:

messenger ribonucleic acid

NDI:

National Death Index

SNP:

single nucleotide polymorphism

SSN:

social security number

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Authors and Affiliations

  1. Department of Anesthesiology, University of North Carolina at Chapel Hill, N2201 UNC Hospitals CB 7010, Chapel Hill, NC, 27599-7010, USA

    Andrey V. Bortsov M.D., Ph.D., Richard L. Boortz-Marx M.D., Harendra Arora M.B.B.S. & Samuel A. McLean M.D., M.P.H.

  2. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Robert C. Millikan DVM, Ph.D.

  3. Department of Anesthesiology, University of Pittsburg, Pittsburgh, PA, 15260, USA

    Inna Belfer M.D., Ph.D.

Authors
  1. Andrey V. Bortsov M.D., Ph.D.
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  2. Robert C. Millikan DVM, Ph.D.
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  3. Inna Belfer M.D., Ph.D.
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  4. Richard L. Boortz-Marx M.D.
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  5. Harendra Arora M.B.B.S.
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  6. Samuel A. McLean M.D., M.P.H.
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Correspondence to Andrey V. Bortsov M.D., Ph.D. .

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Editors and Affiliations

  1. , School of Pharmacy, University of Queensland, Cornwall Street 20, Woolloongabba, QLD4102, Australia

    Marie-Odile Parat

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Bortsov, A.V., Millikan, R.C., Belfer, I., Boortz-Marx, R.L., Arora, H., McLean, S.A. (2013). Genetic Polymorphisms in the µ-Opioid Receptor Gene and Breast Cancer Survival. In: Parat, MO. (eds) Morphine and Metastasis. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5678-6_7

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