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.

Genetic unraveling of colorectal cancer.

Colorectal cancer is a common disease in both men and women (being the third most common cancer in men and the second most common among women) and thus represents an important and serious public health issue, especially in the western world. Although it is a well-established fact that cancers of the large intestine produce symptoms relatively earlier at a stage that can be easily cured by resection, a large number of people lose their lives to this deadly disease each year. Recent times have seen an important change in the incidence of colorectal cancer in different parts of the world. The etiology of colorectal cancer is multifactorial and is likely to involve the actions of genes at multiple levels along the multistage carcinogenesis process. Exhaustive efforts have been made out in the direction of unraveling the role of various environmental factors, gene mutations, and polymorphisms worldwide (as well as in Kashmir-"a valley of gastrointestinal cancers") that have got a role to play in the development of this disease so that antitumor drugs could be developed against this cancer, first, and, finally, the responsiveness or resistance to these agents could be understood for combating this global issue.

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.

A comparative overview of general risk factors associated with the incidence of colorectal cancer.

Cancers found in colorectal region remain largely localized to the large intestine and rectum. They are derived from the epithelium and are considered to be among the most frequently detected cancers. They are known to occur in approximately 5 % population of the Western world. After metastasis, a patient's 5-year postsurgical survival chances unfortunately fall from 90 to 10 % or even less. Adenocarcinoma, the most common cell type of colon cancer, alone constitutes 95 % of the cases. Lymphoma and squamous cell carcinoma can also be found in some cases. Because 5 % of persons are predisposed to development of colorectal cancer, this disease has often been addressed as an important public health issue. Factors that are known in particular to increase a person's risk to develop this cancer are as follows: an individual's age, dietary habits, any complaint of obesity, diabetes, previous history of cancer or intestinal polyps, personal habit of alcohol consumption and smoking, family history of colon cancer, race, sex, and ethnicity. Since the risk of colorectal cancer is increasing steadily in Kashmir, India, like in some other corners of Asia, exhaustive efforts are being made to find the association of above given and other risk factors with the development of this gastrointestinal tract cancer. Adoption of Western life style, diet mimicry, together with a habit of having physically inactive life style and consumption of red meat in particular can be blamed as being active players to a considerable extent.

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.

Cyclin D1 G870A polymorphism and risk of colorectal cancer: a case control study.

The present study aimed to analyse the role of cyclin D1 A870G polymorphism in modulating the susceptibility to colorectal cancer (CRC) in the Kashmiri population. The genotype distribution of the cyclin D1 gene in 130 CRC cases in comparison with 160 healthy controls was investigated. No direct significant association between cyclin D1 genotypes and CRC was observed; however, the AG and AA genotypes were found to be associated with an increased risk of CRC compared to the GG genotype, with an almost 2-fold increase in OR. This study suggests that the cyclin D1 polymorphism is associated with an increased risk of CRC in the Kashmiri population.

Esophageal cancer: associated factors with special reference to the Kashmir Valley.

Esophageal cancer is one of the most common cancers worldwide. It is a multifactorial disease, and no single agent has been identified so far as the sole cause of the cancer. Many factors like smoking, the consumption of alcohol, fungal-contaminated, spicy and various nitrosamine-containing food stuffs and hot beverages, nutritional deficiency of some vitamins like ß-carotene, vitamin A, C and E and minerals like zinc, selenium and molybdenum, the use of opium, HPV infection and various genetic factors have been found associated with the occurrence of the disease worldwide. Wide geographic differences and substantial changes in the incidence of esophageal cancer occurring over time have been suggested. Among the risk factors in India, betel quid chewing carries a relatively high risk. High incidences in Kashmir have been associated with the consumption of hot salted tea, sun-dried, smoked foods, tobacco in the form of hukka and various genetic factors. The exact cause of esophageal squamous cell carcinoma is unknown. Much work has been carried out on the role of various environmental factors, gene mutations, and polymorphisms worldwide, including Kashmir. Although the Kashmir valley is present on the border of the 'high risk esophageal cancer belt' and esophageal squamous cell carcinoma represents the most commonly occurring malignancy in Kashmir, the amount of information available on various associated factors is still very little as there is a paucity of various epidemiological and molecular studies being carried out in this field.

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.