Polyphenol intake and gastric cancer: A case-control study in the Brazilian Amazon region.

BACKGROUND: Polyphenol intake has been associated with a decreased risk of some types of cancer, including gastric cancer (GC). However, few studies address this topic in the Latin American population. In the present study, we evaluated the association between polyphenol intake and the risk of GC in the Brazilian Amazon region. METHODS: A case-control study was conducted in Belém (Amazon region) from July 2017 to February 2021. A total of 193 GC cases and 194 controls of both sexes, between 18 and 75 years old, were included in the study. Dietary data were collected using a validated food-frequency questionnaire and polyphenol intake identified using the Phenol-Explorer database. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI), with adjustement for potential confounders. RESULTS: Cases and controls had similar total polyphenol intake (356.4 mg/1000 kcal/d and 331.1 mg/1000 kcal/d, respectively; p = 0.086). After adjusting for potential confounders, high consumption of flavan-3-ols (highest vs. lowest tertile: OR 0.41, 95% CI 0.18-0.94) and hydroxybenzoic acids (highest vs. lowest tertile: OR 0.24, 95% CI 0.10-0.56) was associated with a decreased risk of GC. The opposite was true regarding the intake of flavones (OR 2.46, 95% IC 1.17-5.18) and other polyphenols (OR 2.54, 95% IC 1.16-5.54). When stratifying according to anatomical topography, we observed that the intake of total flavonoids, flavan-3-ols, and flavanones reduced the risk of cardia GC while that of hydroxybenzoic acids reduced the risk of non-cardia GC. In addition, the intake of flavones and other polyphenols was associated with an increased risk of non-cardia GC. According to histologic subtypes, hydroxybenzoic acid intake was associated with a reduced risk of intestinal-type GC (OR 0.21, 95% IC 0.07-0.64), while flavone consumption was associated with an increased risk of diffuse-type GC (OR 2.59, 95% IC 1.05-6.42). CONCLUSIONS: Our findings suggest that in the Brazilian Amazon region the high intake of flavan-3-ols and hydroxybenzoic acids is associated with a reduced risk of GC, suggesting a potential beneficial role of these compounds against GC.

Association between the TPMT*3C (rs1142345) Polymorphism and the Risk of Death in the Treatment of Acute Lymphoblastic Leukemia in Children from the Brazilian Amazon Region.

Acute lymphoblastic leukemia (ALL) is the leading cause of death from pediatric cancer worldwide. However, marked ethnic disparities are found in the treatment of childhood ALL with less effective results and higher mortality rates being obtained in populations with a high level of Native American ancestry. Genetic variations of the patient can affect resistance to ALL chemotherapy and potentially play an important role in this disparity. In the present study, we investigated the association of 16 genetic polymorphisms with the cell and metabolic pathways of the chemotherapeutic agents used in the treatment of ALL with the risk of death in treating childhood ALL in patients with a high contribution of Amerindian ancestry, coming from the Brazilian Amazon. The study included 121 patients with B-cell ALL treated with the BFM-2002 protocol. We are the first to identify the association between the TPMT gene rs1142345 polymorphism and the high risk of death in treating childhood ALL. Patients with the CC genotype had an approximately 25.5 times higher risk of dying during treatment of the disease than patients with other genotypes (p = 0.019). These results may help elucidate how the patient's genetic characteristics contribute to the mortality disparity in populations with a high contribution of Native American ancestry. The rs1142345 variant of the TPMT gene could be used as a potential marker to early stratify patients at high risk of death in treating childhood ALL in the investigated population.

GEJ cancers: gastric or esophageal tumors? searching for the answer according to molecular identity.

The 7th edition of Union for International Cancer Control (UICC) staging system moved gastroesophageal junction (GEJ) cancers from gastric to esophageal group. Since clinical management is strongly influenced by this staging system, we looked at molecular fingerprints of GEJ tumors and compared to gastric and esophageal profiles. We aimed at elucidating whether GEJ cancers cluster with gastric or esophageal groups according to mRNA and microRNA expression pattern, since this might represent tumor identity. The clinical and expression data were downloaded from The Cancer Genome Atlas (TCGA) with 395 stomach, 184 esophagus and 521 colon samples for mRNA analyses and 392 stomach, 175 esophagus and 459 colon samples for microRNA comparisons. Both Principal Component Analysis (PCA) and Heat Map plots were performed in R platform, using Log2 transformation of RPKM normalized data. Differential Expression Analysis was also performed in R, using RAW data and the DESeq2 package. The mRNAs and microRNAs were tagged as differentially expressed if they met the following criteria: i) FDR adjusted p-value < 0.05; and ii) |Log2 (fold-change)| > 2. Esophagus squamous cell carcinoma (ESCC) clustered apart of the others tumors, while adenocarcinomas (AC) clustered all together according to both mRNAs and microRNAs expression patterns. The HMs of the differentially expressed mRNAs and microRNAs also demonstrated that ESCC belongs to a different group, while AC molecular signature of esophagus looks like AC of the cardia and non cardia regions. Even distal gastric cancers are quite similar to AC of the lower esophagus, demonstrating that esophagus AC relies much closer to gastric cancers than to esophagus cancers. By using robust molecular fingerprints, it was strongly demonstrated that GEJ tumors looks more like gastric cancers than esophageal cancers, despite of tumor heterogeneity.

DNA mismatch repair gene methylation in gastric cancer in individuals from northern Brazil.

Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.