μ-Opioid Receptor Gene A118G Polymorphism Predicts Survival in Patients with Breast Cancer

Abstract

Background Preclinical studies suggest that opioids may promote tumor growth. Genetic polymorphisms have been shown to affect opioid receptor function and to modify the clinical effects of morphine. In this study we assessed the association between six common polymorphisms in the μ-opioid receptor gene, including the well known A118G polymorphism, and breast cancer survival. Methods A total of 2,039 women ages 23–74 yr (38% African American, 62% European American, 55% postmenopausal) diagnosed with breast cancer between 1993 – 2001 were followed through 2006. Genotyping was performed using the TaqMan platform (Applied Biosystems Inc., Foster City, CA). Kaplan-Meyer curves, log-rank tests, and Cox proportional hazard models were used to examine the association between each genotype and survival. Results After Bonferroni adjustment for multiple testing, patient genotype at A118G was associated with breast cancer-specific mortality at 10 yr. Women with one or more copies of the G allele had decreased breast cancer-specific mortality (p < .001). This association was limited to invasive cases only; effect size appeared to increase with clinical stage. Cox regression model adjusted for age and ethnicity also showed decreased mortality in A/G and G/G genotypes compared to A/A genotype (hazard ratio = 0.57 [0.38, 0.85] and 0.32 [0.22, 0.49], respectively; p = .006). Conclusions These results suggest that opioid pathways may be involved in tumor growth. Further studies examining the association between genetic variants influencing opioid system function and cancer survival are warranted.

μ-Opioid Receptor Gene A118 G Variants and Persistent Pain Symptoms Among Men and Women Experiencing Motor Vehicle Collision

“…All study participants provided blood for DNA genotyping; the genotyping call rate at A118G was >98% and the SNP was in Hardy-Weinberg equilibrium. Consistent with HapMap database and a previous large population-based study, 8 the prevalence of the G allele at A118G this European American sample was ~23% (214/948).…”

A Randomized Controlled Trial of Postoperative Thoracic Epidural Analgesia Versus Intravenous Patient-controlled Analgesia After Major Hepatopancreatobiliary Surgery

“…[46] Furthermore, in oncologic care there is emerging data that many cancers have high levels of mu opioid receptor expression, [47,48] that when activated by opiate narcotics could potentially mediate tumor growth and spread. [49,50] As more is learned about the interaction between these receptors and perioperative narcotics, it may become imperative that oncologic surgeons seek alternative methods to reduce perioperative opioid delivery.…”

μ-Opioid Receptor Gene A118G Polymorphism Predicts Pain Recovery After Sexual Assault

“…As noted above, the decreased G allele prevalence in African Americans versus European Americans in our study sample is consistent with previous data from other cohorts. 4 If individuals with a G allele experience a reduction in stress-induced hyperalgesia mediated by endogenous opioids, then the reduced G allele prevalence among African Americans may be 1 factor contributing to the increased burden of pain experienced by African Americans. 18 While women with a G allele at A118G had lower ASD symptom severity and PTSD symptom severity scores than women without a G allele, differences were modest and not statistically significant.…”