title: Missense mutations (p.H371Y, p.D438Y) in gene CHEK2 are associated with breast cancer risk in women of Balochistan origin.
abstract: CHEK2 encodes a serine/threonine-protein kinase which plays a critical role in DNA damage signaling pathways. CHEK2 directly phosphorylates and regulates the functions of p53 and BRCA1. Most women with breast and/or ovarian cancer are not carriers of mutant BRCA1 or BRCA2. Multiple studies have shown that a CHEK2*1100delC confers about a two-fold increased risk of breast cancer in unselected females and a tenfold increase in males. Moreover, studies have shown that first-degree relatives of bilateral breast cancer cases who carried the CHEK2*1100delC allele had an eight-fold increased risk of breast cancer. It has been suggested that CHEK2 functions as a low-penetrance susceptibility gene for cancers and multiplies the risks associated with other gene(s) to increase cancer risk. The main goal of this study was to evaluate and to compare the role of truncating mutations, splice junction mutations and rare missense substitutions in breast cancer susceptibility gene CHEK2. Present study was performed on 140 individuals including 70 breast cancer patients both with and without family history and 70 normal individuals. Written consent was obtained and 3 ml intravenous blood was drawn from all the subjects. DNA was extracted from all the samples through inorganic method published already. Primers were synthesized for all the 14 exons of CHEK2 gene. Coding and adjacent intronic sequences of CHEK2 gene were amplified and sequenced. Two genetic variants (p.H371Y, p.D438Y) were found in exon 10 and exon 11 of gene CHEK2 which were not found in any of the 70 control individuals from same geographical area and ethnic group. The genetic variant c.1312G>T (p.D438Y) identified in a patient with a family history of breast cancer. To our knowledge, this is first mutation scanning study of gene CHEK2 from Balochistan population.
authors.affiliation: Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan.
authors.forename: Abdul Hameed
authors.initials: AH
authors.lastname: Baloch
authors.forename: Shakeela
authors.initials: S
authors.lastname: Daud
authors.forename: Nafeesa
authors.initials: N
authors.lastname: Raheem
authors.forename: Muhammad
authors.initials: M
authors.lastname: Luqman
authors.forename: Adeel
authors.initials: A
authors.lastname: Ahmad
authors.forename: Abdul
authors.initials: A
authors.lastname: Rehman
authors.forename: Jameela
authors.initials: J
authors.lastname: Shuja
authors.forename: Saeeda
authors.initials: S
authors.lastname: Rasheed
authors.forename: Akhtar
authors.initials: A
authors.lastname: Ali
authors.forename: Naseebullah
authors.initials: N
authors.lastname: Kakar
authors.forename: Hafiz Khush
authors.initials: HK
authors.lastname: Naseeb
authors.forename: Mohammad Alam
authors.initials: MA
authors.lastname: Mengal
authors.forename: Muhammad Arif
authors.initials: MA
authors.lastname: Awan
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wasim
authors.forename: Dost Mohammad
authors.initials: DM
authors.lastname: Baloch
authors.forename: Jamil
authors.initials: J
authors.lastname: Ahmad
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D012307:Risk Factors
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human