The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs).

Interleukins (ILs)-which are important members of cytokines-consist of a vast group of molecules, including a wide range of immune mediators that contribute to the immunological responses of many cells and tissues. ILs are immune-glycoproteins, which directly contribute to the growth, activation, adhesion, differentiation, migration, proliferation, and maturation of immune cells; and subsequently, they are involved in the pro and anti-inflammatory responses of the body, by their interaction with a wide range of receptors. Due to the importance of immune system in different organisms, the genes belonging to immune elements, such as ILs, have been studied vigorously.

Toll-Like Receptors (TLRs): Structure, Functions, Signaling, and Role of Their Polymorphisms in Colorectal Cancer Susceptibility.

Toll-like receptors (TLRs) are the important mediators of inflammatory pathways in the gut which play a major role in mediating the immune responses towards a wide variety of pathogen-derived ligands and link adaptive immunity with the innate immunity. Numerous studies in different populations across the continents have reported on the significant roles of TLR gene polymorphisms in modulating the risk of colorectal cancer (CRC). CRC is one of the major malignancies affecting the worldwide population and is currently ranking the third most common cancer in the world.

Preclinical Evidence for the Pharmacological Actions of Glycyrrhizic Acid: A Comprehensive Review.

Glycyrrhiza glabra L. (Family: Fabaceae) is one of the important traditional medicinal plant used extensively in folk medicine. It is known for its ethnopharmacological value in curing a wide variety of ailments.

Promoter methylation and Ile105val polymorphism of gene in the modulation of colorectal cancer risk in ethnic Kashmiri population.

Background: Glutathione-S-transferases (GSTs) are the most important phase II enzymes of the xenobiotic pathway responsible for the detoxification of carcinogens. GSTP1 gene polymorphisms are mostly associated with a lack or an alteration of enzymatic activity toward several substrates thus resulting in increased cancer susceptibility. GSTP1 promoter methylation is also frequently associated with tumor development or poor prognosis in a wide range of tumors.

Strong association of tissue inhibitor of metalloproteinase (TIMP)-2 and -3 promoter single nucleotide polymorphisms with risk of colorectal cancer in ethnic Kashmiri population - a case control study.

The tissue inhibitors of metalloproteinases (TIMPs) including TIMP2 and TIMP3 are the key physiological inhibitors of matrix metalloproteinases (MMPs) and along with MMPs, TIMPs play a vital role in the coordinated proteolytic breakdown and remodeling of the extracellular matrix (ECM) and the basement membrane that represent the barriers to any malignant tumor invasion and progression. These enzymes are vital for tumor invasion and metastasis and also play a critical role in several other stages of tumor development and progression. The studies on the association of various polymorphisms in human TIMP2 and TIMP3 genes including TIMP2-418G/C and TIMP3-1296T/C single nucleotide polymorphisms (SNPs) and CRC risk are limited, mixed, and inconclusive.

XPD-The Lynchpin of NER: Molecule, Gene, Polymorphisms, and Role in Colorectal Carcinogenesis.

In mammals the bulky DNA adduct lesions known to result in deleterious phenotypes are acted upon and removed from the genomic DNA by nucleotide excision repair (NER) pathway. TFIIH multi-protein complex with its important helicase-Xeroderma Pigmentosum Protein (XPD) serves as the pivotal factor for opening up of the damaged lesion DNA site and carry out the repair process. The initial damage verification step of the TFIIH is in part dependent upon the helicase activity of XPD.

Association of IL1 beta gene polymorphism and allograft functions in renal transplant recipients :a case control study from Kashmir Valley.

Background: Cytokines have been found to be the important mediators during renal graft outcome. Therefore, we designed this study to investigate the role of recipients' IL-1 β promoter (-511) and IL-1 β exon-5 (+3954) polymorphisms with the risk of graft outcome.

Methodology: We enrolled one hundred recipients of living-related renal transplants together with the age and sex matched controls from the healthy population not having any renal abnormality for this study.

Strong association of interleukin-6 -174G/C promoter single nucleotide polymorphism with a decreased risk of colorectal cancer in ethnic Kashmiri population: A case control study.

Chronic inflammation increases the risk of development of various cancers, including colorectal cancer. Interleukin-6 has been described as a key regulator of colorectal cancer development and is important in the process of colorectal tumorigenesis largely through the regulation of tumor-promoting inflammation. Several studies have reported the association of various polymorphisms in human interleukin-6 gene including IL-6 -174G/C single nucleotide polymorphism with various cancers, including colorectal cancer, but the results are mixed and inconclusive.

Epigenetics in diagnosis of colorectal cancer.

Colorectal cancer (CRC) is a third most common epithelial carcinoma. CRC is known to develop from the early precancerous lesion to full blown malignancy via definite phases due to cumulative mutations and aberrant methylation of number of genes. The use of serum biomarkers that is non-invasive to discriminate cancer patients from healthy persons will prove to be an important tool to improve the early diagnosis of CRC.

Tumor necrosis factor-α (TNF-α)-308G/A promoter polymorphism in colorectal cancer in ethnic Kashmiri population - A case control study in a detailed perspective.

Background: Inflammation constitutes one of the important components of colorectal cancer (CRC) pathogenesis. Tumor necrosis factor-α (TNF-α), a cytokine and an important inflammatory mediator plays a pivotal role in the malignant cellular proliferation, angiogenesis, tissue invasion and metastasis in CRC. The studies on association of various polymorphisms in human TNF-α gene including TNF-α-308G/A single nucleotide polymorphism (SNP) are limited, mixed and inconclusive.

Matrix metalloproteinase (MMP) -2, -7 and -9 promoter polymorphisms in colorectal cancer in ethnic Kashmiri population - A case-control study and a mini review.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a pivotal role in the transformation and progression of tumors at all stages, especially during the invasion and metastasis. The aim of this study was to determine the genetic association of MMP2, MMP7 and MMP9 promoter polymorphisms with colorectal cancer (CRC) susceptibility and development risk in ethnic Kashmiri population. The genotype frequencies of MMP2-1306C/T, MMP7-181A/G and MMP9-1562C/T SNPs were compared between 142 CRC patients and 184 healthy controls by using PCR-RFLP method.

Allelic loss at PTEN locus leads to progression of colorectal carcinoma among North Indian patients.

We evaluated the loss of heterozygosity (LOH) at 10q locus of microsatellite markers; D10S198, D10S192, and D10S541 of PTEN gene in 223 North Indian colorectal cancer (CRC) specimens. DNA was isolated and microsatellite-specific markers polymerase chain reaction was performed. Out of total 223 cases 102 showed LOH for at least one of the locus.

Polymorphism of the DNA Repair Gene XRCC1 (Arg194Trp) and its role in Colorectal Cancer in Kashmiri Population: a Case Control Study.

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented.

Materials And Methods: In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population.

IL-1β polymorphism and expression associated with decreased risk of gastric carcinoma: a case control study in the ethnic Kashmiri population, India.

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.

XRCC3 Thr241Met gene polymorphism and risk of colorectal cancer in Kashmir: a case control study.

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.

DNA repair gene--XRCC1 in relation to genome instability and role in colorectal carcinogenesis.

Colorectal carcinogenesis is a multifactorial and multi-gene process, involving 3 major genetic instability pathways: chromosomal instability, microsatellite instability and CpG island methylator phenotype. Inefficient DNA repair is one of the causes of genetic instability leading to tumorigenesis. Defects in DNA repair genes are associated with cancer development.

Telomeres and Estrogens: The Unholy Nexus in Pathogenesis of Atherosclerosis.

Atherosclerosis (AS) is a complex inflammatory process and is categorized as a multifactorial disease involving the interplay of genetic and environmental factors. There are many factors which play role in predisposition and development of AS. In this review we have tried to address the basic pathophysiology of AS lesions and the role played by two important factors - telomeres and estrogens in the development of this disease.

RAD51 G135C gene polymorphism and risk of colorectal cancer in Kashmir.

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.

Mismatch repair pathway: molecules, functions, and role in colorectal carcinogenesis.

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.

A case of primary amenorrhea with 46+XY genotype from Kashmir Valley.

Primary amenorrhea is one of the common reproductive disorder affecting females. It leads to the absence of menarche in the reproductive age group in females and/or complete absence of reproductive organs. There are many causes which lead to PA, including genetic aberrations which are the leading factors.

Association of a VDR gene polymorphism with risk of colorectal cancer in Kashmir.

Roles of the vitamin D receptor in etiology of cancers, including colorectal cancer, have been repeatedly stressed in different parts of the world. A case control study aimed to evaluate the relationship between the two was therefore initiated in Kashmir, known both for its increasing incidence of gastrointestinal cancers and deficiency of micro-nutrients especially vitamin D. The study included a total of 617 subjects (312 colorectal cancer cases and 305 controls), with sampling carried out over a period of 5 years.

Folate: metabolism, genes, polymorphisms and the associated diseases.

Folate being an important vitamin of B Complex group in our diet plays an important role not only in the synthesis of DNA but also in the maintenance of methylation reactions in the cells. Folate metabolism is influenced by several processes especially its dietary intake and the polymorphisms of the associated genes involved. Aberrant folate metabolism, therefore, affects both methylation as well as the DNA synthesis processes, both of which have been implicated in the development of various diseases.

Colorectal cancer: molecular mutations and polymorphisms.

Colorectal cancer (CRC) is one of the major causes of mortality and morbidity, and is the third most common cancer in men and the second most common cancer in women worldwide. The incidence of CRC shows considerable variation among racially or ethnically defined populations in multiracial/ethnic countries. The tumorigenesis of CRC is either because of the chromosomal instability (CIN) or microsatellite instability (MIN) or involving various proto-oncogenes, tumor-suppressor genes, and also epigenetic changes in the DNA.

Arg399Gln polymorphism of XRCC1 gene and risk of colorectal cancer in Kashmir: A case control study.

The aim of this study was to investigate the role of the XRCC1 Arg399Gln polymorphism in the susceptibility of a Kashmiri population to colorectal cancer (CRC). We investigated the genotype distribution of the XRCC1 gene in 130 CRC cases in comparison with that of 150 healthy subjects. There was no direct significant association between the XRCC1 genotypes and CRC; however, the Arg/Gln genotype was associated with an elevated risk of CRC (OR>1.

Colorectal cancer: a researcher's perspective of the molecular angel's gone eccentric in the Vale of Kashmir.

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.