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CACNG2 polymorphisms associate with chronic pain after mastectomy.

Department of Anesthesiology, Center for Translational Pain Medicine, Duke University, Durham, NC, United States. Department for Cell and Developmental Biology, Institute of Life Sciences and Center for Research on Pain, The Hebrew University of Jerusalem, Jerusalem, Israel. Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland. Department of Perioperative, Intensive Care and Pain Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States. Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark. Department of General and Visceral Surgery, Centre for Minimal Invasive Surgery, Marienhospital Stuttgart, Stuttgart, Germany. Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC, Canada. National Center for Complementary and Integrative Health, NIH, Bethesda, MD, United States.

Pain. 2019;(3):561-568
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Abstract

Chronic postmastectomy pain (PMP) imposes a major burden on the quality of life of the ever-increasing number of long-term survivors of breast cancer. An earlier report by Nissenbaum et al. claimed that particular polymorphisms in the gene CACNG2 are associated with the risk of developing chronic PMP after breast surgery (Nissenbaum J, Devor M, Seltzer Z, Gebauer M, Michaelis M, Tal M, Dorfman R, Abitbul-Yarkoni M, Lu Y, Elahipanah T, delCanho S, Minert A, Fried K, Persson AK, Shpigler H, Shabo E, Yakir B, Pisante A, Darvasi A. Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2. Genome Res 2010;20:1180-90). This information is important because in principle, it can inform the surgical, radiological, and chemotherapeutic decision-making process in ways that could mitigate the increased risk of chronic pain. In this study, we revisited this claim by independently evaluating the proposed marker haplotype using 2 different patient cohorts recruited in different research settings. Meta-analysis of these new postmastectomy cohorts and the original cohort confirmed significant association of the CACNG2 haplotype with PMP. In addition, we tested whether the same markers would predict chronic postsurgical pain in men who underwent surgery for inguinal hernia repair, and whether there is significant genetic association with cutaneous thermal sensitivity in postmastectomy and postherniotomy patients. We found that the biomarker is selective because it did not predict pain after laparoscopic hernia repair and was not associated with pain sensitivity to experimentally applied noxious thermal stimuli. We conclude that the A-C-C haplotype at the 3 single-nucleotide polymorphisms (rs4820242, rs2284015, and rs2284017) in the CACNG2 gene is associated with increased risk of developing PMP. This information may advance current knowledge on pathophysiology of PMP and serve as a step forward in the prediction of clinical outcomes and personalized pain management.

Methodological quality

Publication Type : Multicenter Study

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