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Irtiza S.,Jamia Hamdard University | Irtiza S.,Medical College | Samie A.U.,Sher i Kashmir Institute of Medical science | Ali S.,Medical College | And 3 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2015

The aim of this research was to investigate the possible association between gastric carcinoma (GC) and polymorphisms of the IL-1β gene in the Kashmiri population using peripheral blood DNA from 150 gastric carcinoma cases and 250 population controls with detailed data for clinicopathological characteristics of the disease. Two SNPs in the IL-1β gene were selected for this study. Expression of IL-1β was studied in 50 gastric carcinoma cases using immunohistochemistry and RT-PCR and then correlated with genotype. The frequency of the IL-1β-511 C allele was significantly higher in the GC case group (53.3%) than in controls (45.4%) with an odds ratio (OR) of 0.73 and a P value of 0.03. Multivariate regression analysis showed associations of gastric carcinoma with mutant form of IL-1β-511 TT (OR 0.309; P value <0.001) and the CC genotype of IL-1β-31 (OR 0.313; P value of 0.002). Haplotype analysis of IL-1β-31 and IL-1β-511 showed decreased association of IL-1β-31 T with IL-1β-511 C with gastric carcinoma (OR 0.728; P value 0.03). Expression study of 50 samples by immunohistochemistry (IHC) and RT-PCR showed association with grade III and stage III+IV. After correlating the expression with polymorphism no association was found.

Nissar S.,Sher i Kashmir Institute of Medical science | Nissar S.,University Of Kashmir | Baba S.M.,Sher i Kashmir Institute of Medical science | Akhtar T.,University Of Kashmir | And 3 more authors.
European Journal of Cancer Prevention | Year: 2014

RAD51 - a DNA double-strand breaks repair gene plays an important role in homologous recombination, a process frequently involved in cancer transformation. The aim of this study was to compare the distribution of the genotype of the RAD51 G135C polymorphism between colorectal cancer (CRC) patients and controls. We also tested the association between the G135C polymorphism of the RAD51 gene and the risk of CRC, and various clinicopathological parameters. Polymorphism was evaluated by restriction fragment length polymorphism PCR in 100 CRC patients and 120 age-matched and sex-matched controls. There was a significant association between RAD51 genotypes and CRC cases (P<0.05). Also, the GC genotype was associated with an increased risk of CRC (odds ratio >3.84). Our results suggest that the G135C polymorphism of the RAD51 gene is associated with an increased risk of CRC in our population. Copyright © Lippincott Williams & Wilkins.

Nissar S.,University Of Kashmir | Sameer A.S.,Sher I Kashmir Institute of Medical science Associated Medical College | Lone T.A.,Sher i Kashmir Institute of Medical science | Chowdri N.A.,Sher i Kashmir Institute of Medical science | Rasool R.,University Of Kashmir
Asian Pacific Journal of Cancer Prevention | Year: 2014

XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms that play roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors, including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotal role in maintaining genomic stability through different pathways of base excision repair (BER). The aim of this study was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. We investigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjects and found a significant association between XRCC3 genotypes and CRC (p ≤ 0.05). Both heterozygous genotype (Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated risk of CRC [OR = 2.53; OR = 2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significant association with the risk of CRC (p = 0.003). This study displayed a significantly elevated risk for CRC in individuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.

Sameer A.S.,Sher I Kashmir Institute of Medical science Associated Medical College | Nissar S.,University Of Kashmir | Fatima K.,University Of Kashmir
European Journal of Cancer Prevention | Year: 2014

The microsatellite instability (MSI) pathway is one of the important mutational pathways that play a critical role in colorectal carcinogenesis. About 15% of colorectal cancers (CRCs) are characterized by MSI. MSI tumors usually arise because of a genetic defect in mismatch repair (MMR) genes, one of the main DNA-repairing systems. MMR is a highly conserved biological pathway that plays a key role in maintaining genomic stability by correcting the base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Mutations in at least five pivotal genes of MMR, namely, in those encoding mutS homolog 2 (MSH2), mutL homolog 1 (MLH1), mutS homolog 6 (MSH6), postmeiotic segregation increased 1 (PMS1), and postmeiotic segregation, increased 2 (PMS2) have been found in CRC, highlighting the importance of understanding the basic structure and functions of the essential molecules that make up the MMR system. In this review, we have attempted to focus on this aspect, that is, the role that MMR molecules play in CRC carcinogenesis. Copyright © Lippincott Williams & Wilkins.

Sameer A.S.,Sher I Kashmir Institute of Medical science Associated Medical College
Tumor Biology | Year: 2013

Colorectal cancer (CRC), being the most common cancer, is the major cause of mortality and morbidity worldwide. In Kashmir, CRC has been found to be the third most common gastrointestinal cancer after esophageal and gastric. The etiology of CRC involves two pathways: chromosomal instability (CIN) and microsatellite instability. CIN occurs in 80-85 % of CRC resulting in either gross changes in chromosome structure and number or point mutations in the chromosomes. Many molecular studies have been carried out on CRC in Kashmir so as to elucidate the role of tumor suppressor genes and oncogenes in modulating the carcinogenesis. We searched the various literature databases including Medline, PubMed, ASCO abstracts, and ESMO abstracts for the papers regarding colorectal cancer published in English using the terms "Kashmir," "colorectal cancer," "colon cancer," "rectal cancer," "carcinogenesis," "epidemiology," "genetics," "mutation," and "polymorphism." Here in this review, I have shed light on the different studies carried on CRC in our Kashmiri population in an attempt to share what we know so far about the molecular carcinogenesis of CRC in Kashmir. © 2013 International Society of Oncology and BioMarkers (ISOBM).

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