title: 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-Meier curves, log-rank tests, and Cox proportional hazard models were used to examine the association between each genotype and survival.
  
  
  RESULTS
  After Bonferroni correction 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 < 0.001). 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 with A/A genotype (hazard ratio = 0.57 [0.38, 0.85] and 0.32 [0.22, 0.49], respectively; P = 0.006).
  
  
  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.
authors.affiliation: Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7010, USA. abortsov@aims.unc.edu
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Bortsov
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.forename: Inna
authors.initials: I
authors.lastname: Belfer
authors.forename: Richard L
authors.initials: RL
authors.lastname: Boortz-Marx
authors.forename: Harendra
authors.initials: H
authors.lastname: Arora
authors.forename: Samuel A
authors.initials: SA
authors.lastname: McLean
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D017450:Receptors, Opioid, mu / Q000235:genetics*; D015996:Survival Rate / Q000639:trends; D055815:Young Adult
chemical_list: D017450:Receptors, Opioid, mu