Dietary habits, lifestyle, and polymorphisms in VDR (ApaI), CYP24A1 (rs6013897, rs158552, rs17217119) and CYP27B1 (rs10877012) were associated with a higher risk of CRC.

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.

ABSTRACT.We investigated a possible association between alcoholism, cigarette smoking, obesity and CYP2E1 RsaI and 96-bp insertion genetic polymorphisms with risk for colorectal cancer (CRC). Patients with CRC (70 women and 61 men) were matched for gender and age to 206 healthy controls. The mean age of the two groups was 62 years. Meat intake, cigarette smoking and alcohol drinking were assessed using a specific frequency questionnaire. The body mass index was also calculated. DNA was extracted from peripheral blood; RsaI polymorphism genotypes were evaluated by PCR-RFLP and 96-bp insertion genetic polymorphisms were evaluated by specific primers. The distributions of CYP2E1 RsaI c1/c1, c1/c2 and c2/c2 genotypes were 90.2, 9.2 and 0.6%, respectively, in controls and 83.9, 13.7 and 2.4% in CRC cases. Allele c2 was associated with increased risk for CRC [odds ratio (OR) = 1.88, 95% confidence interval (95%CI) = 1.02-3.45]. The CYP2E1 RsaI c2/c2 genotype was associated with an increased risk for rectal cancer (OR = 3.23, 95%CI = 1.26-9.03). The 96-bp insertion was slightly more frequent in the CRC group (9.3 vs 11.4%, P = 0.19), especially in females (6.4 vs 11.5%, P = 0.34). Smoking, alcohol drinking or high intake of red meat and CYP2E1 polymorphisms were 3139 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 3138-3145 (2012) CYP2E1 RsaI c2/c2 genotype associated with CRC not associated with increased risk for CRC. The 96-bp insertion was marginally more frequent (P = 0.07) in undernourished CRC subjects. We concluded that the risk for CRC is higher among individuals with allele c2. The CYP2E1 RsaI c2/c2 genotype was associated with an increased risk for rectal cancer.

Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis. Objective: To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins. Patients and Methods: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues. Results: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2. Conclusions: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.

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