Role of the VDR Bsm I and Apa I polymorphisms in the risk of colorectal cancer in Kashmir.

OBJECTIVE: A case-control study aiming to evaluate the relationship between Bsm I and Apa I restriction fragment gene polymorphisms and colorectal cancer (CRC) was carried out in Kashmir, including a total of 368 subjects (180 cases and 188 controls). METHODS: DNA samples extracted from the blood of the subjects were analyzed for 3' untranslated region (3' UTR) Apa I and Bsm I polymorphisms using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). RESULTS: A statistically significant 2.7-fold increased risk was observed in individuals found homozygous for the presence of the 'b' allele, in comparison to subjects homozygous for the 'B' allele (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.49-4.86 (Bsm I)), and a statistically insignificant 2-fold increased risk was found among individuals with the 'aa' genotype, as compared to subjects with the 'AA' genotype (OR 2.017, 95% CI 0.86-4.7). Our study also yielded statistically significant results when the Apa I polymorphism was stratified by age (≤ 50 years) and dwelling area (rural area), and the Bsm I polymorphism by gender (male gender), suggesting a possible role of Apa I and Bsm I polymorphisms in the etiology of CRC in Kashmir. CONCLUSION: We conclude that Apa I and Bsm I single-nucleotide polymorphisms (SNPs) in the vitamin D receptor gene (VDR) might be associated with susceptibility to CRC among Kashmiris.

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. DNA samples from the blood of the subjects were analyzed for start codon Fok I VDR polymorphism. We obtained a 1.3 fold increased risk among individuals homozygous for f variants as compared to subjects homozygous for F allele (odds ratio OR 1.3, 95%CI, 0.861-1.65). Our study also showed statistically significant results when dwelling and tumor location characteristics were stratified with Fok I polymorphism, all of which suggests a possible role of Fok I polymorphism in the etiology of CRC in Kashmir.

ECRG1 and its relationship with esophageal cancer: a brief review.

Esophageal cancer ranks 8th among the most frequently occurring cancers of the world. The exact cause of esophageal squamous cell carcinoma (ESCC) is unknown; however, some factors like smoking, alcohol intake, consumption of fungal-contaminated, spicy, or nitrosamine-containing foodstuffs and hot beverages, together with various genetic factors, have been found associated with the occurrence of this disease in various parts of the world. Much work has been carried out to elucidate the role of various gene mutations and polymorphisms in esophageal mucosal cancer. Previous studies have suggested that esophageal cancer-related gene 1 (ECRG1), as a novel candidate of the tumor suppressor gene family, is expressed in normal esophagus, liver, colon and lung tissues, but the expression is seen to be down-regulated in tumors, especially in ESCC, and in adjacent tissues. The Arg290Gln polymorphism in exon 8 of the ECRG1 gene has been studied in particular in a number of cases and has been observed to play an active role in the development of ESCC. This suggests that substitution of the arginine in the conserved catalytic domain of the ECRG1 protein might reduce its catalytic capacity by impacting its 3-dimensional conformation, thereby causing the genetic susceptibility to ESCC.

Relation between IRF-1 gene and acute myelocytic leukemia in Kashmiri population.

The IRF-1 protein, a mammalian transcriptional factor encoded by a gene located in 5q23-q31, has antioncogenic properties. Involved in regulation of differentiation and proliferation, IRF-1 acts as a tumor suppressor gene and is inactivated by deletion of its one or more exons (exon skipping) in many hematological malignancies, including acute myelocytic leukemia (AML) and myelodysplastic syndromes (MDS). DNA samples, extracted from peripheral blood, taken from 50 Kashmiri AML subjects, were analysed using the polymerase chain reaction and compared with examples of age and gender matched healthy controls from the same population. Three different exon regions (2, 3 and 4) of the IRF-1 gene that were previously shown to be prone to deletion were selected for amplification and analysis. Deletion was observed in 31(62%) out of 50 AML patients (p=0.016). Exon 3 was most frequently deleted (58%), followed by exon 2 (28%), while exon 4 was least affected (12%), providing insights into critical roles in leukemogenesis. The number of deleted exons was variable, but single exon deletions were more frequent (30%). Of interest, IRF-1 gene deletions were not observed in 19 (38%) patients. In our study, the frequency of deletions of these three exons was slightly higher than in an Indian population (52%), but lower than in Sweden in Europe (95%). This study also explored the prevalence and clinical profile of IRF-1 deletions in AML patients. Adults had a significantly higher incidence than children (p=0.0168) and IRF-1 deletions were associated with low Hb (p< 0.0001), high TLC (p=0.0033) and a low platelet count (p=0.0076).

The ECRG1 290Arg/Gln polymorphism is related to risk of esophageal squamous cell carcinoma in Kashmir.

ECRG1 (esophageal cancer related gene 1) is a novel candidate member of the tumor suppressor gene family previously found to be down regulated in human esophageal cancer (ESCC). So far no evidence regarding the role of the ECRG1 gene in this cancer has been reported from the Kashmir valley, located on the border of the high risk 'esophageal cancer belt'. A case control study was therefore carried out with genomic DNA from 165 newly diagnosed ESCC patients (cases) and 200 control subjects. DNA was analyzed for ECRG1 polymorphisms by RFLP PCR, gel electrophoresis and direct sequencing. A statistically significantly increased risk of ESCC was found to be associated with the ECRG1 Arg/Gln and Gln/Gln genotype occurrence compared to the Arg/Arg genotype (odds ratio (OR) 1.698, 95% confidence interval (CI) 1.112-2.593); P= 0.0138) was observed. Statistically significant results were also obtained between the ECRG1 polymorphism and histophathological grade, smoking, dysphagia, low fruit/vegetable intake and salt tea consumption.