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.

Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population.

The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (APC) and ß-catenin plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the APC and ß-catenin genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR) of the APC gene and exon 3 of the ß-catenin gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the APC gene was also carried out using methylation-specific PCR (MS-PCR). The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86). Promoter hypermethylation of APC was observed in 54.65 per cent (47 of 86) of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the APC gene (p ≤ 0.05). Although the number of mutations in the APC and ß-catenin genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, APC, of the Wnt pathway in the development of CRC in the Kashmiri population.

Promoter methylation profile of GSTP1 and RASSF1A in benign hyperplasia and metastatic prostate cancer patients in a Kashmiri population.

Promoter hypermethylation is a marginal approach to inactivating tumor suppressor genes in cancer. DNA hypermethylation is a well-recognized epigenetic malfunction observed in several malignancies, most predominantly in prostate cancer. Aberrant DNA methylation patterns are considered to be the earliest somatic genome changes in prostate cancer. The function of promoter hypermethylation in malignant transformation of the prostate has been widely studied, from its presence in benign hyperplasia (BHP) to development and to the advanced stages of tumor formation. In the present study, we examined the promoter hypermethylation status of the glutathione S-transferase P1 (GSTP1) and RASSF1A genes in 45 BHP samples, 50 proven prostate tumor samples and 80 normal samples. Hypermethylated GSTP1 was found in 29/50 (58.0%) prostate carcinoma cases and 12/45 (26.6%) BHP cases. The RASSF1A gene was methylated in 17/50 (34.0%) prostate cancer samples and 7/45 (15.5%) BHP samples. On the basis of these findings, we propose that the epigenetic regulation of the GSTP1 and RASSF1A genes through promoter hypermethylation may play a crucial role in the progression of prostate cancer, and has probable involvement in BHP.

Does infection with hepatitis A virus provide protection against hepatitis E virus?

Hepatitis A virus (HAV) and hepatitis E virus (HEV) share some common epidemiologic features, but the dramatic age-related difference in their disease prevalences suggests that the immune response to HAV may provide some cross-protection against HEV.