Crosstalk of Cyclin-dependent kinase inhibitor 1A (CDKN1A) gene polymorphism with p53 and CCND1 polymorphism in breast cancer

N. Akhter, S.A. Dar, S. Haque, M. Wahid, A. Jawed, M.S. Akhtar, R.A. Alharbi, A.A.A. Sindi, A. Alruwetei, H.M. Zubair Choudhry, A. Ahmad

Department of Biosciences, Jamia Millia Islamia, New Delhi, India. nakhter@bu.edu.sa/naseem.du@gmail.com

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• Oncology

OBJECTIVE: Mutations and polymorphisms in genes of cell- cycle and apoptosis regulatory pathway influence the breast cancer risk. Analysis of single low penetrance mutant alleles may not reflect the precise risk association when analyzed alone.

PATIENTS AND METHODS: A total of 115 DNA samples extracted from breast cancer patients and an equal number of age and sex-matched normal controls were used for polymorphic analysis. Genotyping for p21 rs1801270 and CCND1 rs603965 was done by PCR-RFLP method while AFLP method was used for p53 rs1042522 single nucleotide polymorphism detection. Statistical methods included simple mean±SD and correlation coefficient to analyze the risk of association of p21, p53 and CCND1 SNPs and breast cancer.

RESULTS: Individuals harboring SNPs in p21, p53 and CCND1 genes namely rs1801270, rs1042522 and rs603965, respectively were rendered increasingly susceptible to developing breast cancer when compared with normal controls.

CONCLUSIONS: Our report emphasizes the need of combinational analysis of low-penetrance mutant alleles to assess accurately their association with breast cancer risk. Future case-control studies analyzing gene-environment interactions across different populations may confirm reported risk associations of studied polymorphisms with developing breast cancer.

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