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.
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.
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.
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