Analysis of APOBEC3A/3B germline deletion polymorphism in breast, cervical and oral cancers from South India and its impact on miRNA regulation
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Breast cancer and cervical cancer are the leading causes of death in women worldwide as well as in India, whilst oral cancer is the top most common cancer among Asian especially in Indian men in terms of both incidence and mortality rate. Genetic factors determining the predisposition to cancer are being explored to identify the signature genetic variations associated with these cancers. Recently, a germline deletion polymorphism in APOBEC3 gene cluster which completely deletes APOBEC3B coding region has been studied for its association with cancer risk. We screened the germline deletion polymorphism in 409 cancer patients (224 breast cancer, 88 cervical cancer and 97 oral cancer samples), 478 controls and 239 cervical cancer tissue DNAs of South Indian origin. The results suggest that the APOBEC3A/3B deletion polymorphism is not significantly associated with cancer risk in our study population (OR 0.739, 95 % CI, p value 0.91457). Considering the viral restriction property of APOBEC3s, we also screened cervical cancer tissue DNAs for the human papilloma virus infection. We observed a gradual increase in the frequency of HPV16 infection from AA/BB cases (66.86 %) to AA/-- cases (71.43) which signifies the impact of this deletion polymorphism in HPV infection. In addition, we performed in silico analysis to understand the effect of this polymorphism on miRNA regulation of the APOBEC3A/3B fusion transcript. Only 8 APOBEC3B targeting miRNAs were observed to regulate the fusion transcript of which miR-34b-3p and miR-138-5p were found to be frequently downregulated in cancers suggesting miRNA-mediated deregulation of APOBEC3A expression in cancer patients harbouring this particular deletion polymorphism.
KeywordsAPOBEC3A APOBEC3B Deletion polymorphism Cancer risk Human Papilloma virus microRNA
This work was supported by a research grant from Department of Atomic Energy, Board of Research in Nuclear Sciences, Mumbai (grant no. 35/14/10/2014-BRNS/0210) and partly by Department of Biotechnology, New Delhi (grant no. BT/PR4820/MED/12/622/2013) sanctioned to AKM. We gratefully acknowledge the infrastructural facilities of our Department supported through SAP and FIST grants from University Grants Commission and Department of Science and Technology, New Delhi, respectively and the Multidisciplinary Research Unit of our institute for the Real Time PCR facility. We also thank Mr. Vishnuprabu Durairajapandian, Mr. M. Nagarajan and Ms. V. Vaishnavi for their comments, advice and technical support. SR and GA are supported by research fellowships from University Grants Commission, New Delhi, AKDMR, VV and MM were supported by research fellowships from Council of Scientific and Industrial Research, New Delhi.
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