Review on Variants in Genes Associated with Cancer Risk and Red Meat Metabolism

With the advent of human genome sequencing project, came the wave of personalized genomics. Scientists have now gone beyond scanning of individual genes and epigenetic variations that might alter an individual's predisposition to developing complex diseases. Nutritional genomics is a science which is fast catching up. Efforts to explain the diet-gene interactions often recapitulate the effects of genetic makeup in determining the exact fate of the meal we ate last. Diet-gene interactions play a major role in the metabolism and detoxification of food-derived mutagens and carcinogens. Heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), and N-nitroso compounds (NOCs) are a class of mutagens or carcinogens found in red and processed meat that can lead to various types of cancers. Harboring unfavourable mutations or single nucleotide polymorphisms (SNPs) involved in metabolism of HCAs, PAHs, and NOCs can promote cancers. Increasing risks of several types of cancers, such as cancer of the colorectum, breast, prostate, esophagus, and lung, have been associated with high intake of red and processed meat. We attempt to compile some of the variants based on reports published during the past five years on variations involved in red meat metabolism which aims to provide useful insight in aiding us to regulate our red meat intake to avoid spurring of cancer

Protein expression and gene analyses of HER2, NM23, and K-RAS in gastric cancer and Helicobacter pylori-associated gastritis

Gastric cancer is ranked as the fourth most common cancer worldwide and the seventh most common cancer in the Malaysian population. Due to its vague and nonspecific symptoms, over 80% of gastric cancer cases were detected in advanced stage, leading to poor survival rate in the patients. Increasing evidence have shown that studies on the molecular biology aspects of Helicobacter pylori-associated chronic gastritis, which is a precursor of gastric cancer, may improve the early diagnosis of gastric cancer. To date, the existing evidence, however, have yet to determine the specific molecular biomarkers that may assist in the diagnosis of early gastric cancer. This preliminary study was done to investigate the role of HER2, nm23 and K-Ras as possible molecular biomarkers in gastric cancer and H. pylori-associated chronic gastritis. A total of 32 cases of gastric cancer and 62 cases of H. pylori-associated chronic gastritis were analyzed using immunohistochemical staining to investigate the protein expressions of HER2, nm23 and K-Ras. Mutational analysis on 15 cases of gastric cancer and 10 cases of H. pyloriassociated chronic gastritis with prominent alterations in protein expressions was performed using polymerase chain reaction and direct sequencing. Our study demonstrated significant increase in the protein expression of nm23 in 62.5% (20/32) of gastric cancer and 33.9% (21/62) H. pylori-associated chronic gastritis and K-Ras in 62.5% (20/32) of gastric cancer and 24.1% (15/62) of H. pylori-associated chronic gastritis using Mann-Whitney U test (P < 0.05). The HER2 was overexpressed in 25.0% (8/32) cases of gastric cancer. However, none of the H. pylori-associated chronic gastritis (0.0%; 0/62) showed HER2 positivity. Using Spearmann’s rank correlation, age was significantly correlated with the nm23 expression in H. pylori-associated chronic gastritis (P = 0.002). Gender was significantly correlated with the K-Ras expression in gastric cancer (P=0.026). For the mutational analysis, no mutation was detected in the HER2 and K-Ras gene. Only one gastric cancer case (6.7%) showed a genetic variation with a C A transition in the exon 1 of the nm23 gene. In conclusion, our findings suggest that nm23 and K-Ras may play role as possible early biomarkers in gastric cancers and precancerous lesions since significant increase was observed in their protein expressions. However, the absence or low incidence of mutations may indicate that mutations in HER2, nm23 or K-Ras gene have insignificant role in the progression of gastric cancer. Further studies should be performed to further elucidate the role of HER2, nm23 and K-Ras as biomarkers in gastric cancer

Inflammatory role of transforming growth factor beta-1 (TGF-β1) in multistep progression of gastric oncogenesis: an immunohistochemical study

The purpose of this study was to investigate differential expression of TGF-β1 in gastric tissues resected from patients diagnosed with chronic gastritis and gastric cancer (adenocarcinoma) and elucidate the potential role of TGF-β1 in steering towards cancer promoting or cancer suppressing microenvironment. Each group of disease serves as representative model involved in multistep progression of gastric oncogenesis. Immunohistochemistry of TGF-β1 on 162 gastric tissues were performed and analyzed microscopically using semi-quantitative system. Tabulated values which represent each pathological group were then assessed statistically to detect significance of expression. Significance association of expression among groups of age and gender were also included in this study. Chi-square and Mann-Whitney U tests with (p > 0.05) confirmed that TGF-β1 expression was dependent on tissue types and decrement of expression was detected between normal tissues to gastritis and cancer. Higher expression was also observed in diffuse type in comparison to intestinal cancer type. For normal samples, significant difference of expression was found between the two genders; male and female. TGF-β1 have the potential as molecular marker for detecting and monitoring inflamed microenvironment. Expression level in gastric cancer may be target for future therapeutic strategy in preventing cancer progression