It is estimated that about 5–10% of breast cancer cases may be due to inherited predisposition. Until now, two main susceptibility genes have been identified: BRCA1 and BRCA2. The first linkage and mutational studies suggested that mutations in these two genes would account for the majority of high-risk breast cancer families, but recent studies show how the proportion of families due to BRCA1 or BRCA2 mutations strongly depends on the population and the types of family analyzed. It is now clear that, in the context of families with a modest cancer profile, which are the most commonly found in the clinical practice, the percentage of mutations found is much lower than that suggested by the first studies. In the present study, we analyze a group of 32 Spanish families, which contatined at least three cases of female breast cancer (at least one of them diagnosed before the age of 50 years), for the presence of mutations in the BRCA genes. The total proportion of mutations was low (25%), although the percentage of mutations in the BRCA1 and BRCA2 genes was higher, considering the breast and ovarian cancer families and the male breast cancer families respectively. Our results are in agreement with the idea that a great proportion of moderate-risk cancer families could be due to low penetrance susceptibility genes distinct from BRCA1 or BRCA2. © 2000 Cancer Research Campaign

Multiple endocrine neoplasia type 1 (MEN 1) is characterised by the combination of tumours of the parathyroid, endocrine pancreas and anterior pituitary glands. In 1988 the MEN 1 gene was mapped to chromosome 11q13 and it was cloned in 1997. This gene contains 10 exons and extends across 9 Kb of genomic DNA; it encodes for a product of 610 amino acid named menin whose function is unknown. We have studied 10 unrelated MEN 1 kindreds by a complete sequencing analysis of the entire gene; mutations were identified in nine of them: five deletions, one insertion, two nonsense mutation and a complex alteration consisting of a deletion and an insertion that can be explained by a hairpin loop model. Two of the mutations have been previously described; the other seven were novel, and they were scattered throughout the coding sequence of the gene. As in previous series, no correlation was found between phenotype and genotype.

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Objective To evaluate the benefit in terms of self-esteem, quality of life (QoL) and health perception, in a physical activity (FA) prescription intervention from Primary Care, after three months. Methods Quasi-experimental study before (T0) -after (T1) without a control group, for the evaluation of the pilot phase of the CAS program, implemented (December 2017-May 2018) in 5 primary health centers in Valencia. The questionnaire (T0) was completed with social information, self-esteem (Rosemberg), and QoL (Euroqol-5D, including health perception (HP)). The FA was prescribed with specific hours and days and the participation was monitorized. Three months after starting the FA, the participants completed the same cuestionaire (T1). An descriptive analysis was made, by intention to treat, T0 n = 82 and T1 n = 78, and the scales were compared before and after, using the Wilcoxon Test for related samples. Results The FA prescription was offered to 185 people, acceptance n = 82 (44.3%) and there were 14 dropouts, adherence (83%). The sample at T0 n = 82, people who completed the 3 months, n = 68, and n = 10 people who droppout but answered the questionnaire, (4 not be located them), total analysis T1 n = 78. There were a significant improvement in the QoL (26,5% p ≤ 0.002), the HP (16% p ≤ 0.000) and self-esteem (4,7%p ≤ 0.000) in women when comparing the median of the referred score before and after the intervention. Qol improved more in the low educational level (26.55% p < 0.001), while the perception of health (16% p < 0.000), and self-esteem (9.3% p < 0.038) improved more in the high educational level. Discussion The prescription of FA has an important benefit in improving health with only 3 months of prescription. It also has a greater positive benefit in women and in the population of low educational level, who are those who perform less FA. This study helps build evidence of the positive impact on the health of the social prescription from primary care. Key messages After 3 months of the physical activity prescription the QoL and self-steem improved mainly in women and low educated people. The acceptance to participate was 50% but the adherence was more than 80%.

Background Malignant mesothelioma is a rare type of cancer. The estimated incidence in Spain is 535 cases per year, being more frequent in men and reaching the highest rate of incidence between the ages of 60-70. Objective: to determine the characteristics of those affected by the mesothelioma in the Valencian Region during the period 2005-2016 and identify the temporary evolution. Methods A cross-sectional study was performed. Cases were identified through the Valencian Region’s Cancer Registry (VCR), those registered between 2005-2015 were identified by the ICD9-CM (code 163*) and 2016’s by the ICD10 (code C45). Cases were validated through the review of clinical documentation. The incidence and mortality were calculated and a descriptive analysis was developed including clinical, demographic and social characteristics. Results 379 cases were identified and confirmed. 58.4% of the cases were men and the average age of diagnosis was 67 years. 85.1% were Spanish. 87.3% of cases had died and the average age of death was 70 years. An increasing incidence has been observed, being 11.4/1000000 inhabitants (CI95%:8.4-14.3) in 2016. The malignant mesothelioma morphology distribution was: 45.1% epithelial, 43.8% non-specified, 6.6% fibrous and 4.5% in two-phase. In 90.8% of the cases the assessment used to confirm the diagnosis was the primary tumour’s histology, in 3.7% was a cytology or hematologic analysis, in 2.6% was metastatic tissue histology, in 1.3% were clinical signs, in 0.5% was other clinical test like MRI/CT scan, in 0.3% was a postmortem histology and in 0.8% assessment was unknown. Conclusions The data about mesothelioma included in the VCR could be considered solid due to the results obtained through the validation. The mesothelioma’s malignancy it is evident, despite its low incidence, its mortality rate is high. The increasing trend observed is in agreement with those experts who estimate that the highest rate of incidence will be between the years 2020-2040. Key messages The data about mesothelioma recorded in the Valencian Region’s Cancer Registry could be considered solid due to the results obtained through the validation of information procedure. The increasing trend of malignant mesothelioma observed is in agreement with those experts who estimate that the highest rate of incidence will be between the years 2020-2040.

Colorectal cancer (CRC) is the third major cause of cancer related deaths worldwide. 5-fluorouracil (5-FU) is widely used for the treatment of colorectal cancer but as a single-agent renders low response rates. Despite the achieved improvements over the past years in cancer treatment, the design of novel targeted and combined therapies is still necessary. Choline kinase alpha (ChoKα), a phospholipid-related enzyme that plays a role in cell proliferation and transformation, has been found overexpressed in many different tumors, including colorectal tumors. ChoKα specific inhibitors, MN58b and TCD717, have potent antitumoral activity both in vitro and in vivo against several tumor-derived cell lines including CRC-derived tumour cells. TCD717 has recently entered clinical trials (http://clinicaltrials.gov/ct2/show/NCT01215864). We have evaluated the effect of ChoKα inhibitors in combination with 5-FU as a new alternative for the treatment of colon tumors. The sequential combination of ChoKα inhibitors with 5-FU resulted in a synergistic effect in vitro in three different human colon cancer cell lines, and in vivo against human colon xenografts in nude mice. Key enzymes in the metabolic pathway of 5-FU such as Thymidylate synthase (TS) and Thymidine kinase (TK1) have been related to drug resistance, one of the major problems for the lack of success of 5-FU chemotherapy. TS is a key enzyme in the synthesis of DNA and the target enzyme of 5-FU. Several studies have demonstrated that the expression of TS mRNA or protein, predicts overall survival for colon cancer and correlates with resistance to 5-FU. Acquired resistance to 5-FU can also be caused by overproduction of TS that results from gene amplification. Regarding to 5-FU developed resistance, a salvaged pathway has been reported in which TK1 plays an important role. Thus, both TS and TK1 are directly involved in resistance to 5-FU therapy. To elucidate the mechanism of the observed synergistic effect, we examined the modulation of ChoKα inhibitors on the expression levels of TS and TK1. CRC cell lines treated with the sequential combination of ChoKα inhibitors and 5-FU show both mechanisms of TS inactivation, a formation of ternary complex due to 5-FU mechanism and a significant down-regulation of TS active due to ChoKα inhibitors, resulting in a total depletion of TS protein. We also observed that ChoKα inhibitors affects the levels of TK1, and provide the basis to support a new therapy focused on the combination of ChoKα inhibitors and 5-FU as a new approach for colorectal cancer patients. In addition, we suggest a promising role for ChoKα inhibitors as a new treatment for patients who had failed 5-FU chemotherapy or display high expression levels of TS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3514. doi:10.1158/1538-7445.AM2011-3514