Liver cancer (LC) ranks fifth in frequency in the world with an estimated number of 437,000 new cases in 1990. In developing countries, incidence rates are two- to three-fold higher than in developed countries. The geographic areas at highest risk are located in Eastern Asia, with age-adjusted incidence rates (AAIRs) ranking from 27.6 to 36.6 per 100,000 in men; Middle Africa, with AAIRs ranking from 20.8 to 38.1 per 100,000 in men; and some countries of Western Africa, with AAIRs ranking from 30 to 48 per 100,000 in men. The geographic areas at lowest LC risk are Northern Europe, Australia, New Zealand, and the Caucasian populations in North and Latin America, with AAIRs below 5.0 per 100,000 in men. Excess of LC incidence among men compared to women is universal, with sex ratios between 1.5 and 3.0. Significant variations in LC incidence among different ethnic groups living in the same geographical area and among migrants of the same ethnic groups living in different areas have been extensively described. The variability of LC incidence rates between countries and within countries, strongly suggests differences in exposure to risk factors. The role of chronic infection with the Hepatitis B and hepatitis C viruses (HBV and HCV) in the etiology of LC is well established. The attributable risk estimates for LC for each of these hepatotropic viruses vary among countries but the combined effects of persistent HBV or HCV infections account for well over 80% of LC cases worldwide. Other documented risk factors such as aflatoxin exposure in diets, cigarette smoking, alcohol consumption, and oral contraceptives may explain the residual variation between and within countries. Interactions between some risk factors have been postulated, and are subject of active research. New laboratory techniques and biological markers such as polymerase chain reaction detection of HBV DNA and HCV RNA, as well as specific mutations related to aflatoxin exposure may help to provide quantitative estimates of the risk related to each these factors.

CEA, CA 125, SCC, CYFRA 21-1 and NSE were prospectively studied in 211 patients with non-small cell lung cancer and compared with clinical parameters (age, sex, Karnofsky Index, symptoms and smoking status), histopathological parameters (stage, histology, tumor size and nodal involvement), biological parameters (LDH and albumin) and the therapy used (surgery, chemotherapy or radiotherapy). Tumor marker sensitivity was CYFRA 21-1: 76%, CA 125: 55%, CEA: 52%, SCC: 33% and NSE: 22%. One of the tumor markers was abnormally high in 87% of the patients with locoregional disease and in 100% of the patients with metastases. Except for NSE, all tumor markers showed a clear relationship with tumor stage and histology and therefore enabled a better histological diagnosis. Abnormal CEA serum levels were mainly found in adenocarcinomas, CA 125 in large-cell lung cancers (LCLC) and adenocarcinomas and SCC in squamous tumors. Eighty-five percent of the patients with SCC levels >2 ng/ml had squamous tumors. Likewise, CA 125 levels <60 U/ml or CEA <10 ng/ml excluded adenocarcinoma or LCLC with a probability of 82 and 91%, respectively.

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Adipose tissue plays an important role in tumor progression, because it provides nutrients and adipokines to proliferating cells. Fatty acid binding protein 4 (FABP4) is a key adipokine for fatty acid transport. In metabolic pathologies, plasma levels of FABP4 are increased. However, the role of this circulating protein is unknown. Recent studies have demonstrated that FABP4 might have a role in tumor progression, but the molecular mechanisms involved are still unclear. In this study, we analysed the role of eFABP4 (exogenous FABP4) in breast cancer progression. MCF-7 and MDA-MB-231 breast cancer cells did not express substantial levels of FABP4 protein, but intracellular FABP4 levels increased after eFABP4 incubation. Moreover, eFABP4 enhanced the proliferation of these breast cancer cells but did not have any effect on MCF-7 and MDA-MB-231 cell migration. Additionally, eFABP4 induced the AKT and MAPK signaling cascades in breast cancer cells, and the inhibition of these pathways reduced the eFBAP4-mediated cell proliferation. Interestingly, eFABP4 treatment in MCF-7 cells increased levels of the transcription factor FoxM1 and the fatty acid transport proteins CD36 and FABP5. In summary, we showed that eFABP4 plays a key role in tumor proliferation and activates the expression of fatty acid transport proteins in MCF-7 breast cancer cells. © 2016 Wiley Periodicals, Inc.

BackgroundSince the 1980s, Spain experienced two decades of sharply increasing breast cancer incidence. Declines in breast cancer incidence have recently been reported in many developed countries. We examined whether a similar downturn might have taken place in Spain in recent years.MethodsCases of invasive female breast cancer were drawn from all population-based Spanish cancer registries that had at least 10 years of uninterrupted registration over the period 1980–2004. Overall and age-specific changes in incidence rates were evaluated using change-point Poisson models, which allow for accurate detection and estimation of trend changes. All statistical tests were two-sided.ResultsA total of 80 453 incident cases of invasive breast cancer were identified. Overall age- and registry-adjusted incidence rates rose by 2.9% (95% confidence interval [CI] = 2.7% to 3.1%) annually during the 1980s and 1990s; there was a statistically significant change in this trend in 2001 (95% CI = 1998 to 2004; P value for the existence of a change point <.001), after which incidence declined annually by 3.0% (95% CI = 1.8% to 4.1%). This trend differed by age group: There was a steady increase in incidence for women younger than 45 years, an abrupt downturn in 2001 for women aged 45–64 years, and a gradual leveling off in 1995 for women aged 65 years or older. Separate analyses for registries that had at least 15 years of uninterrupted registration detected a statistically significant interruption of the previous upward trend in breast cancer incidence in provinces that had aggressive breast cancer screening programs and high screening participation rates, including Navarra (change point = 1991, P < .001), Granada (change point = 2002, P = .003), Bizkaia (change point = 1998, P < .001), Gipuzkoa (change point = 1998, P = .001), and Araba (change point = 1997, P = .002).ConclusionsThe recent downturn in breast cancer incidence among Spanish women older than 45 years is best explained by a period effect linked to screening saturation.

Our aim was to estimate the prevalence of mutations in the BRCA1 and BRCA2 genes among unselected incident cases of breast cancer in young women. We identified 158 incident breast cancer cases diagnosed before age 46 years in predefined geographic areas in Girona and Tarragona, Spain, during 1995-1997. Of these, 136 (86%) provided information on family history of cancer and were screened for BRCA1 and BRCA2 mutations. Nine of the 136 (6.6%) were found to carry BRCA deleterious mutations (MUT) (1 BRCA1 and 8 BRCA2), and 20 were detected with rare BRCA variants of unknown significance (UV). Both MUT and US BRCA alterations were more frequent in younger patients: 7 (11.6%) MUT and 12 (19.3%) UV carriers were found in the group of 62 patients younger than 40 years, whereas 2 (2.7%) MUT and 9 (12%) US carriers were identified in the group of 74 patients aged 40 -45. Family history of breast and ovarian cancers suggestive of hereditary condition (at least 2 first-or second-degree relatives affected with breast cancer or at least 1 relative affected with ovarian cancer or early-onset breast cancer) was absent for 5 of 9 MUT carriers. This suggests that BRCA screening policies based on family history of cancer would miss a considerable proportion of BRCA mutations. Mutations in the BRCA1 and BRCA2 genes explain at least 10% of breast cancer cases diagnosed before age 40 years. The contribution of these genes to early-onset breast cancer is likely to be even higher given that certain UV cases might be disease-associated. © 2003 Wiley-Liss, Inc. Key words: BRCA; breast cancer; SpainBreast cancer is the most frequent cancer type among women in the world, affecting up to 12% of all women in Europe and North America. 1 Germline mutations of the BRCA1 and BRCA2 genes substantially increase the lifetime risk of developing breast and ovarian cancers. 2,3 The estimated cumulative risk for breast cancer by age 70 in carriers of these mutations is about 80%. 2-5 Estimates of penetrance and contribution of BRCA1 and BRCA2 to cancer incidence have been mainly based on data from high-risk families and might not reflect the situation in all BRCA1/2 carriers. Several studies on founder mutations in populations like Ashkenazi Jews or Icelanders have provided penetrance estimates that were lower than those obtained in high-risk families. 4,5 The same trend was observed in Australian and UK studies on outbred populationbased series of breast cancers, estimating breast cancer penetrance to be 40 -50% by age 70. 6,7 Several reports estimating the prevalence of BRCA1 and BRCA2 mutations in large population-based samples of breast cancer cases have been published. 6 -11 However, all but the study of Loman et al. 11 confronted the problems of a relatively low proportion of incident cases included in the analysis and limited mutation screening protocols.Our aim was to evaluate in the Spanish population the prevalence of mutations in the BRCA1 and BRCA2 genes among unselected incident cases of breast cancer diagnosed before the age of 46 years....

HPRC can occur in an early onset form. The median age for renal tumor development in these 3 HPRC families was 46 to 63 years. HPRC associated papillary renal tumors may be aggressive and metastasize, leading to mortality. Median survival age was 60 to 70 years. Families with identical germline mutations in MET do not always share a common ancestor. HPRC is characterized by germline mutations in MET and papillary type 1 renal tumor histology.

Hereditary breast and ovarian cancer syndrome (HBOC) is partly due to the presence of mutations in the BRCA genes. Triple-negative (TN) breast cancer (BC) shares histological characteristics with germline BRCA1 mutation-associated tumours. We have investigated the metabolic profiles of human breast cancer (BC) cell lines carrying BRCA1 pathogenic mutations by non-targeted liquid chromatography coupled to mass spectrometry technology. Based on our in vitro results, we performed a targeted metabolomic analysis of plasma samples from TN HBOC patients taking into account their BRCA1 genotype. BRCA1 promoter hypermethylation and the BRCAness phenotype of BC cell lines were also studied. The purpose of this study was to determine the metabolic signature of HBOC syndrome and TNBC patients and to evaluate the potential contribution of the metabolites identified to the genetic diagnosis of breast cancer. The present results show the existence of a differential metabolic signature for BC cells based on the BRCA1 functionality. None of the studied BC cell lines presented hypermethylation of the BRCA1 promoter region. We provide evidence of the existence of free methylated nucleotides capable of distinguishing plasma samples from HBOC patients as BRCA1-mutated and BRCA1 non-mutated, suggesting that they might be considered as BRCA1-like biomarkers for TNBC and HBOC syndrome.