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Introduction Gastric cancer (GC) is the fourth most common cancer in the world and the second leading cause of death due to cancer. The Multi-Drug Resistance 1 (MDR1) gene encodes P-glycoprotein, which confers resistance to antineoplastic drugs, but also affects the kinetic disposition of some drugs and carcinogens. The C3435T polymorphism of the MDR1 gene may influence the transport and excretion of carcinogens, increasing the risk of cancer. The aim of this study was to evaluate the association between this polymorphism and the risk of gastric cancer and tumor aggressiveness. Methods A case-control study was conducted. The case group consisted of patients with non-cardia adenocarcinoma. The control group consisted of healthy subjects. Serology was performed by ELISA for the investigation of infection with Helicobacter pylori. DNA was extracted from peripheral venous blood leukocytes collected with EDTA. The MDR1 polymorphism was analyzed by PCR-RFLP. After amplification, the products were digested with 5 units of the restriction enzyme MboI (New England Biolabs). Genome sequencing was used to confirm the PCR and RFLP techniques using random samples of the two groups. The PCR product of the MDR1 gene was purified using the Big Dye XTerminator Kit and sequenced in an ABI Prism 3100 sequencer. The reverse primer was used for sequencing. The electropherogram was analyzed with the Sequence Scanner v1.0 program. Results Ninety eight patients with non-cardia GC and 203 healthy subjects participated in the study. There was no difference in gender (p=0.12) or age (p=0.125) between the two groups. The genotypes in the control group were in Hardy-Weinberg equilibrium and the frequency of TT, CC and CT genotypes was 19.2%, 33.0% and 47.8%, respectively. In the GC, the frequency of TT, CC and CT genotypes was 15.3%, 32.7% and 52.0%, respectively. No significant difference in the genotypes (p=0.668) or alleles (p=0.745) was observed between the groups. There was no association between the genotypes and the risk of GC in patients infected with H. pylori (p=0.662). Patient survival was not correlated with the genotypes studied (p=0.454). Conclusion The present results provide evidence that the C3435T polymorphism of the MDR1 gene is not associated with GC risk or prognosis in the population studied. No correlation was observed between this polymorphism and infection with H. pylori.

Aim: NICE trial showed that combination of chemoradiation and nimotuzumab, a humanized antibody against EGFR, is safe and appears to increase the combined complete response (cCR) rate, defined as endoscopic and/or pathologic CR, in pts with locally advanced esophageal cancer (ASCO 2014). Here we present the results of the exploratory analyses of molecular markers and their correlation to clinical outcomes. Methods: Tumor samples were obtained before chemoradiation with or without nimotuzumab. All samples were formalin-fixed and paraffin-embedded. Tumor areas were selected and macrodissected, followed by whole DNA extraction and amplification by PCR. Mutations and single nucleotide polymorphisms (SNPs) were searched in codons 12 and 13 of exon 2 for KRAS, and exons 18 to 24 for EGFR through DNA sequencing by Sangeŕs methodology. Fisher's exact test was used to compare groups. Results: Molecular analyses were performed in tumor samples from 51 of the 107 randomized patients, 18 from the control arm (chemoradiation) and 37 from the experimental arm (chemoradiation plus nimotuzumab). No mutations or SNPs were identified in KRAS among the 48 samples analyzed. Indeed, no mutations were found in EGFR, but some SNPs were identified. Except for exon 21, for all other sequenced exons at least one patient had one SNP identified, more frequently in exons 20 and 23. SNPs identified in exon 20 included 167339G > A (rs10251977) and 167339G > A (rs1050171). The latter was the most frequent detected SNP and it was identified in 11 patients (3 in the control group and 8 in the nimotuzumab group). Within each treatment arm, the cCR rates were similar between patients whose tumors harboring or not the SNP rs1050171. Although not statistically significant (P = 0.074), in the nimotuzumab group, cCR rate of tumors harboring rs1050171 was nominally higher than the rate observed for tumors without this SNP (87.5% [7/8] vs. 42.9% [6/14]). Conclusions: No mutations were found in KRAS or EGFR. Several EGFR SNPs were identified, being rs1050171 in exon 20 the most frequently found. Although exploratory, these results suggest an association between response to nimotuzumab and tumor biologic characteristics. Further exploration of this hypothesis is planned in a phase III trial. Disclosure: L.P.D.G. Neusquen: Clinical Research Department of Eurofarma S.A. All other authors have declared no conflicts of interest.

Introduction The colorectal cancer (CRC) tends to increase with population aging reaching currently 1 million cases with 500.000 deaths around the world. In Brazil, the estimation for this year is 30.140 new cases with 12.471 deaths that make this neoplasia the fourth cause of death in the country. Colonoscopy and fecal occult blood (FOBT) test are largely used for colorectal cancer screening. However, the FOBT had a low sensibility and the colonoscopy is expensive and brings great inconvenience to the subjects. New methods involving the DNA of the stools are being studied to increase the diagnosis of cancer with a noninvasive method. Aim: Quantification of the human DNA of the stools of patients with colorectal cancer. Methods We analyzed 97 stool samples of patients, divided in two groups: 51 individuals without CRC that form the control group and 46 patients with colorectal cancer, which form the case group. All the patients from the control group had been submitted to colonoscopy. PCR Real Time was utilized, through the quantification method by amplification of specific sequences of DNA (Quantifier Human Standard - Applied Systems) and by comparison between these groups. Also to compare the quantification by amplification, we used the fluorescent spectrophotometry. The total DNA of the stools had also been quantified. Results The mean total DNA from the stools of the CRC patients was 91.1ng/µL (SD=57.8) and of the control group was 109.7ng/µL (SD=95.3), (p>0.05). The mean human DNA quantification of the case group was 15.03ng/µL (SD=30.7) and for the control group 0.47ng/µL (SD=1.02). This difference between both groups was significant (p Conclusion No difference on total DNA stool quantification was found between the groups. Patients with colorectal cancer had significant more quantities of human DNA compared to patients without cancer. Higher quantities of human DNA were found in patients with CRC localized in descendent, sigmoid and rectal cancer.

Introduction The increasing availability of oral drugs for oncology treatment led to studies about adherence. Low adherence can impact the successful of the treatment. Nurses and pharmaceutics can play a significant role monitoring and identifying barriers and implementing strategies to increase adherence. Capecitabine (a pro-fluoropyrimidine) is an oral drug mostly used in gastro-intestinal and breast cancer. The efficiency of capecitabine is similar of the 5FU and is most convenient to the patient. Aim: to investigate the adherence of the treatment with oral capecitabine for metastatic breast cancer (MBC) and colorectal cancer on adjuvant or palliative treatment. Correlate the adherence of the drug to possible changes in patient's quality of life. Methods This prospective cohort study included patients with metastatic colorectal cancer (MCRC) or non-metastatic colorectal cancer (CRC) and patients with MBC using capecitabine alone or in association with other drugs or radiotherapy (RT). The patients were treated with a 3-weekly regimen of capecitabine 1000 bid mg/m2 for 14 days. The pills were given by the pharmaceutics after a short explanation. Two methods had been done to evaluate adherence before each cycle for 4 cycles: a self-report short questionnaire about the intake of the drugs diary and a manual count of unused medication before the delivery of the next cycle pills. The quality of life questionnaire QLQ-C30 (EORTC) was applied at the first visit before beginning the treatment and after 4 cycles. Results 30 patients had been included, being 6 with MBC, 9 MCRC and 16 CRC. The mean age was 60 years old and 20 were females. Three patients received capecitabine on monotherapy, 18 capecitabine associated to other chemotherapies and 9 capecitabine associated to radiotherapy. After 4 cycles the adherence was 88.3% for metastatic colon cancer, 90.4% for non-metastatic colon cancer, 94.3% for rectal cancer and 96.2% for metastatic breast cancer. No difference was found between adherence and localization of the tumor (p=0.606) or between the capecitabine on monotherapy or in association with others drugs or RT (p=0.105). The high adherence had been probably influenced by the pharmaceutical explanation although a control group without this interview was not done. Dyspnea at the beginning of the treatment had been correlated to a less adherence of the drug during the period studied (r= -0.37, p=0.042). No correlation between adherence and EORTC QLQ-C30 functional or symptom scale rates was found at the last evaluation. Conclusion Although no absolute adherence to oral capecitabine treatment was observed, the level of adherence was considered good. A negative correlation between adherence and dyspnea was found.

Introduction Colorectal cancer (CRC) is one of the most causes of death by cancer in the world. Numerous genetic alterations had been associated to the higher risk of cancer as well as to increase aggressiveness. Lipoxygenase, described in 1976 by Borgeat, is an enzyme responsible for arachidonic acid conversion in prostaglandins and prostacyclins and it is involved in colorectal cancer risk. Studies on isoforms of lipoxygenases that correlates to control mechanisms on cancer emergence and progression have been increasing in recent years. Pro-inflammatory mediators synthesis, leukotrienes are done by lipoxygenases. Leukotrienes stimulate colon cell proliferation and inhibit apoptosis. The aim of this study was to analyze 1708(G>A) 5- LOX in colorectal cancer patients and correlate this polymorphism to lifestyle and diet intake. Methods A case-control study with CRC patients matched by sex and age to healthy controls was developed. DNA was extracted from peripheral leucocytes, purified and the polymorphism was analyzed by PCR and sequencing genetic. Smoking, alcoholism, physical exercises and diet had been evaluated by a specific questionnaire. Results 391 subjects were studied, being 205 with colorectal cancer (56% females) and 110 healthy individuals (52% females). The mean age was 59.8 years old for the CRC group and 62.5 years old for the control group (0.07). In the CRC: 135 individuals (72%) was GG, 46 patients (25%) GA and 5 patients (3%) AA. In the control group 136 individuals (66%) were GG, 65 (32%) GA and 4 (2%) AA (p=0.294). The most frequent allele in both groups was G. There was no difference between genotypes and groups (OR: 0.985; IC95%=0.238- 4.081; p=0.983). We did not find a difference between the genotypes and smoking (p=0.129), alcoholism (p=0.475) and meat intake (p=0.283) in the CRC patients. Conclusion No association was found between 5-LOX genotypes and cancer. In the CRC patients, the genotypes had not been correlated to alcoholism, smoking or meat intake.