title: Association between hTERT polymorphisms and the risk of breast cancer in a sample of Southeast Iranian population.
abstract: BACKGROUND
  Breast cancer (BC) is considered to be one of the most important causes of death worldwide, and it affects the Iranian female population a decade earlier than female in other parts of the world. Human telomerase reverse transcriptase (hTERT) is a main subunit of the telomerase complex. MNS16A is located downstream of the hTERT gene and is recognized as the regulator of hTERT promoter activity. The aim of the present study was to access the possible impact of hTERT variants on BC risk in an Iranian population in southeast Iran.
  
  
  METHODS
  A total of 491 subjects including 266 BC patients and 225 healthy women participated in the study. Polymerase chain reaction (PCR) was used to genotype the MNS16A variable number of tandem repeats and 177 bp ins/del polymorphisms in the hTERT gene. PCR-RFLP and ARMS-PCR were used to genotype hTERT rs2736098 and 2735940, respectively. The association between genotypes and BC was assessed by computing the odds ratio (OR) and 95% confidence intervals (95% CI) from logistic regression analyses. A p-value of <0.05 was considered statistically significant.
  
  
  RESULTS
  The MNS16A genotype frequency distribution in BC patients was: LL, 43.2%; LS, 51.1%; and SS, 5.7%, and in controls: LL, 29.5%; LS, 68.3%; and SS, 2.2%. The LS genotype decreased the risk of BC compared with LL (OR=0.51, 95% CI=0.35-0.75, p<0.001). The hTERT 177 bp ins/del polymorphism was not polymorphic in our population. All subjects had the ins/ins genotype. Our findings indicate that the MNS16A genotype and hTERT rs2736098 variant were associated with BC risk in the study. We also showed that the rs2736098 A/G polymorphism increased the risk of BC (OR=1.80, 95% CI=1.12-2.88, p=0.017, AG vs AA; OR=1.80, 95% CI=1.06-3.06, p=0.033, GG vs AA; OR=1.87, 95% CI=1.19-2.94, p=0.006, AG+GG vs AA). No significant association was found between the rs2735940 C/T variant and BC.
  
  
  CONCLUSIONS
  Our findings indicate that the MNS16A genotype and the hTERT rs2736098 variant influence the risk of BC in an Iranian population in southeast Iran.
authors.affiliation: Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran. mhd.hashemi@gmail.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
authors.forename: Shadi
authors.initials: S
authors.lastname: Amininia
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Ebrahimi
authors.forename: Seyed Mehdi
authors.initials: SM
authors.lastname: Hashemi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Taheri
authors.forename: Saeid
authors.initials: S
authors.lastname: Ghavami
mesh_terms: D000328:Adult; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007492:Iran; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D019098:Telomerase