title: Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer--a Case-Control Study in Jordan.
abstract: Breast cancer is the leading cause of cancer death among women and the second in humans worldwide. Many published studies have suggested an association between MDR1 polymorphisms and breast cancer risk. Our aim was to study the association between genetic polymorphism of MDR1 at three sites (C3435T, G2677A/T, and C1236T) and their haplotype and the risk of breast cancer in Jordanian females.
  
  
  
  A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. The polymerase chain reaction/restriction fragment length polymorphism (PCR- RFLP) technique and sequencing were performed to analyse genotypes.
  
  
  
  The distribution of MDR1 C3435T genotypes differed between cases and controls [cases, CC 45.3%, CT 41.3%, and TT 13.3%; controls, CC 13.4%, CT 43.3%, and TT 30.2%, p < 0.001]. Similarly, the distribution of G2677A/T significantly differed [cases, GG 43.1 %, GT+GA 50.9% and AA+TT 6%; controls, GG 29.6 %, GT+GA 50.9%, and AA+TT 19.4%, p = 0.004]. On the other hand, genotype and allelotype distribution of C1236T was not statistically different between cases and controls (p=0.56 and 0.26, respectively). The CGC haplotype increased the risk to breast cancer by 2.5-fold compared to others, while TGC and TTC haplotypes carried 2.5- and 5-fold lower risk of breast cancer, respectively.
  
  
  
  Genetic polymorphisms of MDR1 C3435T and G2677A/T, but not C1236T, are associated with increased risk of breast cancer. In addition, CGC, TGC and TTC haplotypes have different impacts on the risk of breast cancer. Future, larger studies are needed to validate these findings.
authors.affiliation: Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, the University of Jordan, Amman, Jordan E-mail : mr_abuhaliema@yahoo.com.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Abuhaliema
authors.forename: Al-Motassem F
authors.initials: AM
authors.lastname: Yousef
authors.forename: Nirmeen N
authors.initials: NN
authors.lastname: Elmadany
authors.forename: Nailya R
authors.initials: NR
authors.lastname: Bulatova
authors.forename: Nemah M
authors.initials: NM
authors.lastname: Awwad
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Yousef
authors.forename: Khalil Z
authors.initials: KZ
authors.lastname: Al Majdalawi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000483:Alleles; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007597:Jordan; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B