CACNG2 polymorphisms associate with chronic pain after mastectomy

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. (2010) claimed that particular polymorphisms in the gene CACNG2 are associated with the risk of developing chronic PMP after breast surgery. This information is important as 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 the present study we revisited this claim by independently evaluating the proposed marker haplotype using two 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 as it did not predict pain following 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 three 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 prediction of clinical outcomes and personalized pain management.