Original article Are cell cycle and apoptosis genes associated with prostate cancer risk in North Indian population?  Raju Kumar Mandal, M.Sc. 1 , Rama Devi Mittal, Ph.D.* Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh, India Received 8 April 2010; received in revised form 11 May 2010; accepted 13 May 2010 Abstract Objective: Prostate cancer (CaP) is a heterogeneous, multifactorial, and multifocal disease. Therefore, the search for a combination of functional polymorphisms using cell cycle and apoptotic genes as tumor markers is fundamental for a more precise and reliable diagnosis. In the present study, we investigated the diagnostic value of 3 different genes associated with CaP carcinogenesis, encoding for cell cycle (MDM2, CCND1) and apoptotic (Fas) genes that are differentially expressed in CaP. Methods: In a hospital-based case control study of northern India, blood samples were obtained from 192 CaP patients and 224 cancer-free age matched unrelated healthy controls of similar ethnicity. They were genotyped for MDM2 G309T, CCND1 G870A, Fas A670G, and G1377A polymorphisms using polymerase chain restriction fragment length polymorphism (PCR-RFLP) method. Results: MDM2 309GG variant was at reduced risk for developing CaP (P = 0.041; OR, 0.59). Whereas CCND1 AA genotype demonstrated increased risk (P = 0.018; OR, 1.86). The diplotype analysis of Fas G670A and G1377A (G-A) was observed to be associated with a significant increase in CaP risk (P = 0.024; OR, 1.63). Conclusion: Findings based on current sample size our results suggested a positive association of CCND1AA genotype and diplotype analysis of Fas G670A and G1377A (G-A) to be associated with CaP risk that could influence the pathophysiology, thereby modulating the risk of CaP. © 2012 Elsevier Inc. All rights reserved. Keywords: Polymorphism; Prostate cancer 1. Introduction Prostate cancer (CaP) is the most common non-skin cancer among men, and its incidence is rising rapidly in most countries [1]. The incidence rate of CaP in India is low compared with Western countries, and CaP is the sixth most commonly diagnosed cancer among men [2]. Despite its high morbidity, the etiology of CaP remains largely un- known. It is well established that genetic factors also play an important role in pathogenesis of CaP [3]. Therefore there is increasing interest in the role that genetic variants, such as single nucleotide polymorphic (SNPs) variants, play in CaP risk. DNA initiates a series of signals that call upon an arrest of cell cycle for the completion of repair activities or acti- vate the apoptotic pathway if the damage to DNA is unre- pairable. Cell cycle regulation and apoptosis are essential defenses against cancer [4,5]. Functional relevance of some variants in cell cycle and apoptosis genes has been evalu- ated and inconsistent results have been reported on the associations between these variants and a number of cancer sites. Thus, it is plausible that genetic variation in critical pathways of DNA repair, cell-cycle control, or apoptosis may contribute to inter-individual variation in susceptibility to CaP. The human mouse double-minute 2 protein (MDM2) located on chromosome 12q14.3-q15 is a cellular E3 ligase able to ubiquinate and degrade p53 [6]. As a key negative  This study was supported by Uttar Pradesh Council of Science and Technology (UPCST) grant, Lucknow, India. * Corresponding author. Tel.: +091-522-2668004-8 ext. 4116; fax: +091-522-2668-017. E-mail address: ramamittal@gmail.com (R.D. Mittal). 1 RKM thanks the Council of Scientific and Industrial Research, New Delhi, India for providing Junior Research fellowship during the course of study. Urologic Oncology: Seminars and Original Investigations 30 (2012) 555–561 1078-1439/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.urolonc.2010.05.006