title: The dyslipidemia-associated SNP on the APOA1/C3/A5 gene cluster predicts post-surgery poor outcome in Taiwanese breast cancer patients: a 10-year follow-up study.
abstract: BACKGROUND
  Post-surgery therapies are given to early-stage breast cancer patients due to the possibility of residual micrometastasis, and optimized by clincopathological parameters such as tumor stage, and hormone receptor/lymph node status. However, current efficacy of post-surgery therapies is unsatisfactory, and may be varied according to unidentified patient genetic factors. Increases of breast cancer occurrence and recurrence have been associated with dyslipidemia, which can attribute to other known risk factors of breast cancer including obesity, diabetes and metabolic syndrome. Thus we reasoned that dyslipidemia-associated nucleotide polymorphisms (SNPs) on the APOA1/C3/A5 gene cluster may predict breast cancer risk and tumor progression.
  
  
  METHODS
  We analyzed the distribution of 5 selected APOA1/C3/A5 SNPs in recruited Taiwanese breast cancer patients (n=223) and healthy controls (n=162). The association of SNP (APOA1 rs670) showing correlation with breast cancer with baseline and follow-up parameters was further examined.
  
  
  RESULTS
  APOA1 rs670 A allele carriage was higher in breast cancer patients than controls (59.64% vs. 48.77%, p=0.038). The rs670 A allele carrying patients showed less favorable baseline phenotype with positive lymph nodes (G/A: OR=3.32, 95% CI=1.77-6.20, p<0.001; A/A: OR=2.58, 95% CI=1.05-6.32, p=0.039) and negative hormone receptor expression (A/A: OR=4.85, 95%CI=1.83-12.83, p=0.001) in comparison to G/G carriers. Moreover, rs670 A/A carrying patients had higher risks in both tumor recurrence (HR=3.12, 95% CI=1.29-7.56, p=0.012) and mortality (HR=4.36, 95% CI=1.52-12.47, p=0.006) than patients with no A alleles after adjustments for associated baseline parameters. Furthermore, the prognostic effect of rs670 A/A carriage was most evident in lymph node-negative patients, conferring to the highest risks of recurrence (HR=4.98, 95% CI=1.40-17.70, p=0.013) and mortality (HR=9.87, 95%CI=1.60-60.81, p=0.014) than patients with no A alleles.
  
  
  CONCLUSIONS
  APOA1 rs670 A/A carriage showed poor post-surgery prognosis in Taiwanese lymph node-negative breast cancer patients, whose prognosis were considered better and adjuvant treatment might be less stringent according to currently available assessment protocols. Our findings suggest that APOA1 rs670 indicate a post-surgery risk of breast cancer disease progression, and that carriers of this SNP may benefit from more advanced disease monitoring and therapy regimens than the current regular standards. Furthermore, control of lipid homeostasis might protect APOA1 rs670 minor allele carriers from breast cancer occurrence and progression.
authors.affiliation: Research Center for Medical Laboratory Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Mei-Chi
authors.initials: MC
authors.lastname: Hsu
authors.forename: Kuo-Ting
authors.initials: KT
authors.lastname: Lee
authors.forename: Wei-Chiang
authors.initials: WC
authors.lastname: Hsiao
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Wu
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Sun
authors.forename: I-Ling
authors.initials: IL
authors.lastname: Lin
authors.forename: Kung-Chia
authors.initials: KC
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000235:genetics*; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000235:genetics; D001054:Apolipoproteins A / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D050171:Dyslipidemias / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D005810:Multigene Family; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D013624:Taiwan; D016896:Treatment Outcome
chemical_list: C505693:APOA1 protein, human; C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A