Vol.:(0123456789) 1 3 Breast Cancer https://doi.org/10.1007/s12282-018-0894-0 REVIEW ARTICLE CDKN2A/P16INK4A variants association with breast cancer and their in-silico analysis Ayesha Aftab 1  · Shaheen Shahzad 2  · Hafiz Muhammad Jafar Hussain 3  · Ranjha Khan 3  · Samra Irum 1  · Sobia Tabassum 1 Received: 30 March 2018 / Accepted: 13 July 2018 © The Japanese Breast Cancer Society 2018 Abstract CDKN2A was first identified as melanoma predisposition tumour suppressor gene and has been successively studied. The previous researches have not established any noteworthy association with breast cancer. Therefore, through extensive lit- erature search and in-silico analysis, we have tried to focus on the role of CDKN2A in breast cancer. CDKN2A variants in breast cancer were collected from different databases. The overall percentage of variants (approximately 5.8%) and their incidence frequency in breast cancer cases were found to be very low as compared to the number of samples screened in different studies. Exon 2 was identified as the major region of alternations. Approximately 42.8% were entire gene deletions, while 24.2% were missense mutations. These variants cannot be ignored because of their pathogenic effects as interpreted by the bioinformatics tools used in the present study. Earlier studies have shown that CDKN2A excludes the predisposition of germline variants, but interestingly shares common breast cancer germline variants with other carcinomas. Most of the data have revealed this gene as rarely mutated or deleted in breast cancer. However, few association studies have shown that in addition to being a ‘multiple’ tumour suppressor gene, it is mutated/deleted more in breast cancer cell lines as compared to breast cancer tissues or blood samples; thus, this gene cannot be neglected as a breast cancer candidate gene. The deletion/ malfunctioning of CDKN2A in different tumours including breast cancer has recently led to the discovery of many clinical CDK inhibitors. Furthermore, these collected genetic variants will also be helpful in developing diagnostic, preventive, and treatment approaches for patients. Keywords Breast cancer · Variant analysis · CDKN2A · P16 Introduction Breast cancer is a type of a tumour in which cancerous cells originate from tissues of the breast. Males are at fewer risks of getting breast cancer, but like women, the chances of developing breast cancer increase with age [1]. It is the most common cancer in females worldwide with the highest incidence and mortality rate after lung cancer and has been ranked second among all of the cancers [1, 2]. In general, two genetic oscillations are involved in tumour development, one is activation of oncogenes and second is inactivation of tumour suppressor genes [3]. CDKN2A (cyclin-dependent kinase inhibitor 2A)/p16INK4A/p14ARF is an anti-oncogenic or tumour suppressor gene that was * Shaheen Shahzad drshaheen@iiu.edu.pk Ayesha Aftab ravian09_13@yahoo.com Hafiz Muhammad Jafar Hussain hafizaasi19@gmail.com Ranjha Khan rhanjha@mail.ustc.edu.cn Samra Irum samrairum2@gmail.com Sobia Tabassum sobia.tabasum@iiu.edu.pk 1 Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad 44000, Pakistan 2 Genomics Research Lab, Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad 44000, Pakistan 3 The CAS Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui, China