title: ACC interleukin-10 gene promoter haplotype as a breast cancer risk factor predictor among Jordanian females.
abstract: BACKGROUND
  Interleukin-10 (IL-10) is a multifactorial cytokine with a complex biological role in breast cancer. The aims of this study were to investigate any association between IL-10 gene promoter polymorphisms, 1082A>/G, -819T>C, and -592A>C, or haplotypes and breast cancer risk among Jordanian women and to evaluate any association between the most common haplotype with clinicopathological features of breast cancer.
  
  
  METHODS
  A total of 202 breast cancer patients and 210 age-matched healthy control subjects were genotyped for -1082A/G, -819T/C, and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reaction-restriction fragment length polymorphism. Study patients and control subjects were recruited from Prince Hamzah Hospital, Amman, Jordan (2012-2013). Ethical approval and signed consent forms were signed by all participants. DNA was extracted, and polymerase chain reaction fragments were amplified and restriction digested by MnII, MaeIII, and RsaI.
  
  
  RESULTS
  This study showed no statistically significant difference between -1082A/G, -819T/C, and -592A/C IL-10 genotypes or alleles among breast cancer patients or controls. Four different haplotypes ATA, ACC, GTA, and ACA within the IL-10 promoter gene were determined among both breast cancer and control groups. The most frequent haplotype was ACC among breast cancer patients and controls (41.6% and 40.7%, respectively). No statistical differences in these haplotypes among breast cancer patients or controls were determined. Analysis of the most common ACC haplotype showed statistical difference in positive estrogen receptor (P=0.022), positive progesterone receptor (P=0.004), cancer grade (P=0.0001), and cancer stage (P=0.009) among the ACC haplotype compared to non-ACC haplotype.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report studying the association of IL-10 haplotype with breast cancer risk events among Jordanian females. The most frequent IL-10 haplotype among Jordanian breast cancer females is ACC haplotype. Patients carrying the ACC haplotype are associated with higher positive estrogen and progesterone receptors and advanced breast cancer grade and stage. These patients also had lower survival rate in the Kaplan-Meier survival plot compared to those with non-ACC haplotype.
authors.affiliation: Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, The Hashemite University, Zarqa, Jordan.
authors.forename: Manar Fayiz
authors.initials: MF
authors.lastname: Atoum
keywords: breast cancer; genotypes; haplotypes; interleukin-10