ABSTRACT. Two TP53 gene polymorphisms at codon 47 (TP53 Pro47Ser) and at codon 72 (TP53 Arg72Pro) have been associated with susceptibility to various cancers. We carried out a case-control study and examined the genotype distribution of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms (SNPs), using a PCR-RFLP approach, to determine if these two SNPs are risk factors for colorectal cancer (CRC) development and to look for a possible correlation of these two SNPs with clinicopathological variables of CRC. We investigated the genotype distribution of these SNPs in 86 CRC cases in comparison with 160 healthy subjects in an ethnic Kashmiri population. TP53 Arg72Pro SNP genotype frequencies differed significantly (P = 0.000001) between the groups; the frequency of the Pro/Pro mutant was almost 20% in the general population. We also found significant association of the Pro/Pro mutant with tumor location, nodal status/higher tumor grade and bleeding per rectum/constipation. We conclude that Arg72Pro SNP is associated with susceptibility to developing CRC in this ethnic Kashmiri population.

BackgroundPrimary squamous cell carcinomas of the colorectum are very uncommon. Until now, to the best of our knowledge, only 114 cases of squamous cell carcinoma in the colorectum exist in the reported literature. Here we report a case of squamous cell carcinoma of the rectum in the ethnic Kashmiri population in northern India.Case PresentationThe case of a 60-year-old male patient (Asian) with a pure squamous cell carcinoma of the rectum is presented here. The patient underwent a curative surgery with concomitant chemotherapy. Two years after the initial curative resection of the tumor he is still alive.ConclusionThe prognosis for squamous cell carcinoma of the colorectum is worse than for that of adenocarcinoma, because of the delayed diagnosis. The etiopathogenicity of squamous cell carcinoma of the colorectum is discussed. Surgical resection of the lesion seems to be the treatment of choice. Chemotherapy also helps in improvement of the prognosis.

Background/Aim:Colorectal cancer (CRC) is one of the leading malignancies worldwide and has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. The aim of this study was to identify p53 and K-ras gene mutations in CRC patients in a Kashmiri population, and to assess whether these mutations are linked with clinicopathological parameters.Materials and Methods:Paired tumor and normal tissue samples from a consecutive series of 53 patients undergoing resective surgery for CRC were prospectively studied for p53 and K-ras gene mutations by PCR/single strand conformation polymorphism (SSCP).Results:Less than half (45%, 19/42) of the patients presented mutations in the p53 gene. Twenty eight mutations were found in the p53 gene, which comprised of 23 substitutions (17 transitions + 6 transversions), and five insertions. The 23 substitutions constituted 18 missense mutations, two nonsense mutations, and three silent mutations. Of the 28 mutations (7.14%) observed in this study, 2 were not previously reported for CRC samples and were identified as novel p53 mutations. A few patients (22.64%, 12/53) presented with mutations in K-ras, constituting 13 missense mutations, out of which 11 were G→A transitions, one was a G→C transversion, and one a G→T transversion. More than half (61.5%) of the mutations occurred in codon 12 whereas a few (38.5%) occurred in codon 13. One tumor contained missense mutations in both codons. Comparison of the mutation profiles of our patients with those of other ethnic populations and regions reflected both differences and similarities, indicating co-exposure to a unique set of risk factors.Conclusion:Mutations of the p53 and K-ras genes are some of the most common genetic changes in the development of human CRC. The high frequency of p53 gene mutations implicates p53 as a predominant factor for CRC in the high-risk ethnic Kashmiri population.

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Background: Caveolin-1 (CAV-1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signalling. Aberrant promoter methylation of CAV-1 is associated with inactivation of expression. We previously observed CAV-1 mutations in breast cancers and therefore devised this study to examine the hypermethylation status of the promoter region of CAV-1 with reference to breast cancer progression and development. Methods: Hypermethylation status of CAV-1 was analyzed by methylation specific PCR. Loss of expression of the CAV-1 gene was further evaluated by semi-quantitative rt-PCR. Results: 28/130 (21.5%) breast cancer cases showed promoter hypermethylation with reduced CAV-1 expression levels when compared with adjacent normal breast tissue. CAV-1 gene hypermethylation was significantly related to menopausal status, histopathological grade and age. Conclusion: The rationale of our study is that CAV-1 gene is transcriptionally repressed in breast cancer cells due to hypermethylation. Our results reveal that promoter hypermethylation and loss of expression of the CAV-1 gene is an important alternative mechanism for inactivation of CAV-1 leading to complete gene silencing.