title: Analysis of APOBEC3A/3B germline deletion polymorphism in breast, cervical and oral cancers from South India and its impact on miRNA regulation.
abstract: 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.
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, Tamil Nadu, India.
authors.forename: Sundaramoorthy
authors.initials: S
authors.lastname: Revathidevi
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, Tamil Nadu, India.
authors.forename: Mayakannan
authors.initials: M
authors.lastname: Manikandan
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, Tamil Nadu, India.
authors.forename: Arunagiri Kuha Deva Magendhra
authors.initials: AK
authors.lastname: Rao
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, Tamil Nadu, India.
authors.forename: Vilvanathan
authors.initials: V
authors.lastname: Vinothkumar
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, Tamil Nadu, India.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Arunkumar
authors.affiliation: Centre for Oncology, Government Royapettah Hospital & Kilpauk Medical College, Chennai, Tamil Nadu, India.
authors.forename: Kottayasamy Seenivasagam
authors.initials: KS
authors.lastname: Rajkumar
authors.affiliation: Institute of Social Obstetrics and Government Kasturba Gandhi Hospital for Women and Children, Chennai, Tamil Nadu, India.
authors.forename: Rajendran
authors.initials: R
authors.lastname: Ramani
authors.affiliation: Centre for Oncology, Government Royapettah Hospital & Kilpauk Medical College, Chennai, Tamil Nadu, India.
authors.forename: Ramamurthy
authors.initials: R
authors.lastname: Rajaraman
authors.affiliation: Centre for Oncology, Government Royapettah Hospital & Kilpauk Medical College, Chennai, Tamil Nadu, India.
authors.forename: Chandrasekar
authors.initials: C
authors.lastname: Ajay
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, Tamil Nadu, India. akmunirajan@gmail.com.
authors.forename: Arasambattu Kannan
authors.initials: AK
authors.lastname: Munirajan
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D003564:Cytidine Deaminase / Q000235:genetics*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics* / Q000821:virology
chemical_list: D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D011506:Proteins; C121399:APOBEC3A protein, human; C495794:APOBEC3B protein, human; D003564:Cytidine Deaminase
keywords: APOBEC3A; APOBEC3B; Cancer risk; Deletion polymorphism; Human Papilloma virus; microRNA