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Cancer is a major burden worldwide but there are marked geographical variations in frequency and incidence overall. The aim of this study was to find the frequency and distribution of commonly occurring cancers in Kashmir, with particular emphasis on urinary bladder cancer. A total of 4,407 cases of histologically confirmed new cancer cases were registered at the Medical Records Department (MRD) of SKIMS from a period between January, 2005 and April 2010. Among 4407 cancers, 2,457 (55.7 %) were men and 1,950 (44.3 %) were women. Stomach cancer is the leading one with an average frequency of 19.2 % followed by esophagus and lung as 16.5 % and 14.6 %, respectively. Stomach (23 %) and lung (21 %) are the leading cancers in men while as esophageal cancer tops (18.3 %) in women followed by breast cancer (16.6 %). This distribution of cancer types is strikingly different from that in the rest of India where oropharyngeal cancer is most common form. Among urinogenital cancers, bladder cancer was observed to primarily affect Kashmiri population (5.9 %) followed by prostate cancer (2.1 %) and renal carcinoma (1.1 %). We conclude that Kashmir is a very high risk area of most commonly occurring cancers particularly cancers of gastrointestinal tract which comprise more than half the frequency of all the cancers.

Kangri cancer found only in Kashmir (north India) is a unique thermally induced squamous cell carcinoma of the skin that develops because of chronic and persistent irritation due to the use of a kangri (a brazier) by the Kashmiri people to combat the chilling cold temperature during winter. Being unique to this region, the molecular etiology of the invasive kangri cancer is not known fully. The TP53 gene, codon 72 polymorphism (Arg72Pro), has been found to be associated with cancer susceptibility but has not been investigated in kangri cancer risk. A case control study was conducted to find the genotype distribution of TP53 Arg72Pro SNP and to elucidate the possible role of this SNP as risk factor in kangri cancer development. Using the polymerase chain reaction-restriction fragment length polymorphism approach, we tested the genotype distribution of 106 kangri cancer patients in comparison with 200 cancer-free controls from the same geographical region. A significant difference was observed between the control and kangri cancer patients with odds ratio = 2.02 and 95% confidence interval = 1.2-3.3 (p = 0.01). Interestingly, the proline form was abundantly observed in advanced-grade tumors (p < 0.05). We also found a significant association of the variant allele (GC + CC) with male subjects and patients >45 years of age (p < 0.05). Thus, it is evident from our study that Arg72Pro SNP is implicated in kangri cancer and that the rare, proline-related allele is connected with higher susceptibility to kangri cancer.

The vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. Polymorphisms in the VEGF gene may regulate VEGF production. In this case-control study, we investigated whether functional polymorphisms (+405 C > G and +936 C > T) in the VEGF gene are associated with the risk of lung cancer. Genomic DNA was isolated from the blood of 100 lung cancer patients and 150 healthy controls, and total RNA was isolated from 48 tumor tissues and adjacent normal lung tissues. Two DNA polymorphisms (+405 C > G and +936 C > T) in the 3'-untranslated regions (3'-UTR) and 5'-untranslated regions (5'-UTR) of vascular endothelial growth factor A (VEGFA) were studied using PCR-RFLP method, and mRNA expression of VEGFA was studied by quantitative real-time PCR. Polymorphisms in the 5'-UTR (+405 C > G) and 3'-UTR (+936 C > T) did not show significant difference between lung cancer cases and control samples (P = 0.11 and P = 0.09, respectively). VEGF +405 CG and GG are significantly more in age group >50 years old, in all grades, and in early pathological stages (P = 0.04, P = 0.03, and P = 0.006, respectively). Also, increased expression of VEGFA mRNA was noted in tumorous compared to non-tumorous tissue (P < 0.0001). Overexpression of the gene was considered at ΔC (T) > 6.0. Within the group of patients with conventional tumor, those with histology other than squamous cell carcinoma (SCC) had a higher level of VEGFA mRNA expression than SCC patients (P = 0.04). Overexpression of VEGFA mRNA was noted in lung cancer and more so in lung cancer with adenocarcinoma and large cell carcinoma histology and in pathological stages III and IV. VEGFA +405 C > G SNP showed an association with age, pathological grade, and stage.