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Missense mutations (p.H371Y, p.D438Y) in gene CHEK2 are associated with breast cancer risk in women of Balochistan origin

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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.

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Acknowledgments

We thank all the participants who voluntarily took part in this study. This research work was supported by IARC through research grant (CRT No. Fel/11/01) to Jamil Ahmad and partial financial support was provided by ORIC, BUITEMS. We also thank director CENAR and his team for their kind support.

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Authors and Affiliations

  1. Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan

    Abdul Hameed Baloch, Naseebullah Kakar, Dost Mohammad Baloch & Jamil Ahmad

  2. Center for Advanced Molecular Biology (CAMB), Lahore, Pakistan

    Shakeela Daud

  3. Institute of Biochemistry and Biotechnology (IBBt), UVAS, Lahore, Pakistan

    Shakeela Daud, Saeeda Rasheed, Akhtar Ali & Muhammad Wasim

  4. Medical Centre, BUITEMS, Quetta, Pakistan

    Nafeesa Raheem

  5. Department of Microbiology, BUITEMS, Quetta, Pakistan

    Muhammad Luqman

  6. Mayo Hospital, Lahore, Pakistan

    Adeel Ahmad & Abdul Rehman

  7. Centre for Nuclear Medicine and Radiotherapy (CENAR), Quetta, Pakistan

    Jameela Shuja & Hafiz Khush Naseeb

  8. Centre for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan, Quetta, Pakistan

    Mohammad Alam Mengal & Muhammad Arif Awan

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  1. Abdul Hameed Baloch
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  2. Shakeela Daud
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  13. Muhammad Arif Awan
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  14. Muhammad Wasim
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  15. Dost Mohammad Baloch
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  16. Jamil Ahmad
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Correspondence to Jamil Ahmad.

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Baloch, A.H., Daud, S., Raheem, N. et al. Missense mutations (p.H371Y, p.D438Y) in gene CHEK2 are associated with breast cancer risk in women of Balochistan origin. Mol Biol Rep 41, 1103–1107 (2014). https://doi.org/10.1007/s11033-013-2956-x

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  • DOI: https://doi.org/10.1007/s11033-013-2956-x

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