Opportunistic genetic screening increases the diagnostic yield and is medically valuable for care of patients and their relatives with hereditary cancer.

BACKGROUND: Multigene panel testing by next-generation sequencing (MGP-NGS) enables the detection of germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes beyond those associated with a certain cancer phenotype. Opportunistic genetic screening based on MGP-NGS in patients with suspicion of hereditary cancer reveals these incidental findings (IFs). METHODS: MGP-NGS was performed in patients who fulfilled the clinical criteria to undergo genetic testing according to the Catalan Health Service guidelines. Variants were classified following the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines and the Cancer Variant Interpretation Group UK guidelines. RESULTS: IFs were identified in 10 (1.22%) of the 817 patients who underwent MGP-NGS. The mean age at cancer diagnosis was 49.4±9.5 years. Three IFs (30.0%) were detected in PMS2, two (20.0%) in ATM and TP53 and one (10.0%) in MSH6, NTHL1 and VHL. Seven (70.0%) IFs were single-nucleotide substitutions, two (20.0%) were deletions and one (10.0%) was a duplication. Three (30.0) IFs were located in intronic regions, three (30.3%) were nonsense, two (20.0%) were frameshift and two (20.0%) were missense variations. Six (60.0%) IFs were classified as PVs and four (40.0%) as LPVs. CONCLUSIONS: Opportunistic genetic screening increased the diagnostic yield by 1.22% in our cohort. Most of the identified IFs were present in clinically actionable genes (n=7; 70.0%), providing these families with an opportunity to join cancer early detection programmes, as well as secondary cancer prevention. IFs might facilitate the diagnosis of asymptomatic individuals and the early management of cancer once it develops.

Utility of ctDNA Liquid Biopsies from Cancer Patients: An Institutional Study of 285 ctDNA Samples.

Liquid biopsy has improved significantly over the last decade and is attracting attention as a tool that can complement tissue biopsy to evaluate the genetic landscape of solid tumors. In the present study, we evaluated the usefulness of liquid biopsy in daily oncology practice in different clinical contexts. We studied ctDNA and tissue biopsy to investigate EGFR, KRAS, NRAS, and BRAF mutations from 199 cancer patients between January 2016 and March 2021. The study included 114 male and 85 female patients with a median age of 68 years. A total of 122 cases were lung carcinoma, 53 were colorectal carcinoma, and 24 were melanoma. Liquid biopsy was positive for a potentially druggable driver mutation in 14 lung and colorectal carcinoma where tissue biopsy was not performed, and in two (3%) lung carcinoma patients whose tissue biopsy was negative. Liquid biopsy identified nine (45%) de novo EGFR-T790M mutations during TKI-treatment follow-up in lung carcinoma. BRAF-V600 mutation resurgence was detected in three (12.5%) melanoma patients during follow-up. Our results confirm the value of liquid biopsy in routine clinical oncologic practice for targeted therapy, diagnosis of resistance to treatment, and cancer follow-up.

Identification of germline pathogenic variants in DNA damage repair genes by a next-generation sequencing multigene panel in BRCAX patients.

BACKGROUND: Approximately 5-10% of breast carcinomas have been related to hereditary conditions and are attributable to pathogenic variants in the BRCA1 and BRCA2 genes, which is referred to as hereditary breast and ovarian cancer (HBOC) syndrome. The inclusion of additional genes that can be related to HBOC syndrome is under intense evaluation due to the high proportion of patients with HBOC criteria who do not present pathogenic mutations in BRCA genes, named BRCAX, despite having high clinical suspicion of hereditary cancer. The main aim is to identify new potentially pathogenic gene variants that may contribute to HBOC to improve the efficiency of routine diagnostic tests in this hereditary condition. METHODS: A retrospective cohort of 77 HBOC BRCAX patients was analyzed by next-generation sequencing using a targeted multigene panel composed of 25 genes related to hereditary cancer and deficiencies in DNA repair pathways. RESULTS: We found 9 variants in 7 different genes, which were confirmed by automated sequencing. Six variants were classified as pathogenic or likely pathogenic. Three of them were located in the PALB2 gene, one in the BRIP1 gene, one in the BARD1 gene and 1 in the RAD50 gene. In addition, three variants of uncertain significance (VUS) were detected in the TP53, CHEK2, and CDH1 genes. CONCLUSIONS: We identified that 8% of BRCAX patients were carriers of pathogenic variants in genes other than BRCA1 and BRCA2. Therefore, wide gene panels, including clinically actionable genes, should be routinely used in the screening of HBOC in our population. We observed differences from other studies in the prevalence of mutated genes, most likely due to differences in the selection criteria of the probands and in the population analyzed. The high incidence of deleterious variant detection in PALB2 supports its significant role in breast cancer susceptibility and reinforces its inclusion in the HBOC genetic diagnostic process.

Metabolomics reveals novel blood plasma biomarkers associated to the BRCA1-mutated phenotype of human breast cancer.

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.

Adipose-Derived Fatty Acid-Binding Proteins Plasma Concentrations Are Increased in Breast Cancer Patients.

BACKGROUND: Adipose tissue is an endocrine organ that could play a role in tumor progression via its secreted adipokines. The role of adipose-derived fatty acid-binding protein (FABP) 4 and FABP5 in breast cancer is presently under study, but their circulating levels in this pathology are poorly known. We analyzed the blood concentrations of FABP4 and FABP5 in breast cancer patients to determine whether there is an association between them and breast cancer. MATERIALS AND METHODS: We studied 294 women in the oncology department with a family history of breast cancer; 198 of the women had breast cancer, and 96 were healthy controls. The levels of FABP4, FABP5, lipid profile, standard biochemical parameter, and high-sensitivity C-reactive protein (hsCRP) were determined. We analyzed the association of FABP4 and FABP5 with breast cancer, while adjusting for demographic, anthropometric, and biochemical parameters. RESULTS: Breast cancer patients had a 24.8% (p < .0001) and 11.4% (p < .05) higher blood concentration of FABP4 and FABP5, respectively. Fatty acid-binding protein 4 was positively associated with age, body mass index (BMI), FABP5, very-low-density lipoprotein cholesterol (VLDLc), non-high-density lipoprote in cholesterol (non-HDLc), Apolipoprotein B 100 (ApoB100), triglycerides, glycerol, glucose, and hsCRP (p < .05), and was negatively associated with HDLc (p < .005) in breast cancer patients. Fatty acid-binding protein 5 was positively associated with BMI, FABP4, VLDLc, triglycerides, glycerol, and hsCRP (p < .05), and was negatively associated with HDLc and Apolipoprotein AI (ApoAI) (p < .05) in breast cancer patients. Using a logistic regression analysis and adjusting for age, BMI, hsCRP, non-HDLc, and triglycerides, FABP4 was independently associated with breast cancer (odds ratio [OR]: 1.091 [95% CI: 1.037-1.149]). Moreover, total cholesterol, VLDLc, non-HDLc, ApoB100, triglycerides, and hsCRP were significantly increased in breast cancer patients (p < .005). In contrast, the non-esterified fatty acids concentrations were significantly decreased in breast cancer patients (p < .05). CONCLUSION: Circulating FABP4 and FABP5 levels were increased in breast cancer patients compared with controls. The positive association of FABP4 with breast cancer was maintained after adjusting for important covariates, while the association with FABP5 was lost. Our data reinforce the role of adipose tissue and their adipokines in breast cancer. Despite these data, further studies must be performed to better explain the prognosis or diagnostic value of these blood parameters and their possible role in breast cancer. IMPLICATIONS FOR PRACTICE: We focus on the effect of adipose tissue on cancer, which is increasingly recognized. The association between adipocyte-derived adipokines and breast cancer opens new diagnosis and therapy perspectives. In this study, we provide original data concerning FABP4 and FABP5 plasma concentrations in breast cancer patients. Compared to control group, breast cancer patients show higher FABP4 and FABP5 blood levels. Our data suggest that, particularly, circulating FABP4 levels could be considered a new independent breast cancer biomarker. Our work translates basic science data to clinic linking the relationship between adipose tissue and lipid metabolism to breast cancer.

Trends in net survival from skin malignant melanoma in six European Latin countries: results from the SUDCAN population-based study.

In Europe as a whole, survival from skin malignant melanoma (SMM) has increased constantly since the 1980s. The aim of the SUDCAN collaborative study was to compare the trends in the 5-year net survival from SMM and in related excess mortality rate between six European Latin countries (Belgium, France, Italy, Portugal, Spain, and Switzerland). The data were extracted from the EUROCARE-5 database (end of follow-up: 01 January 2009). First, the net survival was studied over the 2000-2004 period using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain, and Switzerland and from 2000 to 2004 in Belgium and Portugal. The analyses were carried out using a flexible excess rate modeling. Over the 2000-2004 period, the 5-year net survival from SMM ranged from 79 (Portugal) to 90% (Switzerland). In all countries, net survival was higher in women versus men and in young versus old age groups. From 1992 to 2004, the 5-year net survival increased the most in the countries with the lowest survivals in 1992 (+9% in Italy and Spain vs. +2% in Switzerland or +4% in France). The differences between countries decreased between 1992 and 2004. Although survival increased to a lower or higher extent in all countries during the period studied, significant differences in net survival from SMM persisted among the six countries studied. Health policies should mainly enhance early diagnosis by increasing public awareness and with screening campaigns. Furthermore, new immunotherapies, which will be approved soon hopefully, should also be used to improve the outcomes of SMM treatment.

Exogenous FABP4 increases breast cancer cell proliferation and activates the expression of fatty acid transport proteins.

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.

In silico, in vitro and case-control analyses as an effective combination for analyzing BRCA1 and BRCA2 unclassified variants in a population-based sample.

Ascertaining the clinical consequences of BRCA1 and BRCA2 variants of uncertain significance (VUS) is currently indispensable for providing effective genetic counseling and preventive actions for families with hereditary breast and ovarian cancer (HBOC). To this end, we conducted a combination of in silico prediction and cDNA splicing analyses of 13 BRCA1 and 10 BRCA2 VUS identified in our cohort as well as a case-control analysis in a population-based sample of 10 recurrent VUS. We observed consistent results between the in silico predictions and sequencing analyses for all analyzed VUS. An abnormal cDNA pattern was observed for variants c.212+1G>A and c.5278-1G>A in BRCA1 and c.516+2T>A and c.8168A>G in BRCA2 according to in silico splicing prediction. A case-control study of VUS confirmed the polymorphisms of the c.67+62A>G, c.7008-62A>G and c.8851G>A BRCA2 variants previously published. c.4068G>A in the BRCA2 gene can also be considered a polymorphism due to its occurrence at a frequency greater than 1% in our population. Our study shows that employing population-based analysis and a combination of several in silico methods yields highly accurate information, resulting in a reliable tool for selecting variants for cDNA sequencing analysis in routine cancer genetic counseling units.

Correlation between mutational status and survival and second cancer risk assessment in patients with gastrointestinal stromal tumors: a population-based study.

BACKGROUND: Gastrointestinal stromal tumors are sarcomas of the digestive tract characterized by mutations mainly located in the c-KIT or in the platelet-derived growth factor receptor (PDGFR)-alpha genes. Mutations in the BRAF gene have also been described. Our purpose is to define the distribution of c-KIT, PDGFR and BRAF mutations in a population-based cohort of gastrointestinal stromal tumors (GIST) patients and correlate them with anatomical site, risk classification and survival. In addition, as most of the GIST patients have a long survival, second cancers are frequently diagnosed in them. We performed a second primary cancer risk assessment. METHODS: Our analysis was based on data from Tarragona and Girona Cancer Registries. We identified all GIST diagnosed from 1996 to 2006 and performed a mutational analysis of those in which paraffin-embedded tissue was obtained. Observed (OS) and relative survival (RS) were calculated according to risk classifications and mutational status. Multivariate analysis of variables for observed survival and was also done. RESULTS: A total of 132 GIST cases were found and we analyzed mutations in 108 cases. We obtained 53.7% of mutations in exon 11 and 7.4% in exon 9 of c-KIT gene; 12% in exon 18 and 1.9% in exon 12 of PDGFR gene and 25% of cases were wild type GIST. Patients with mutations in exon 11 of the c-KIT gene had a 5-year OS and RS of 59.6% and 66.3%, respectively. Patients with mutations in exon 18 of the PDGFR gene had a 5-year OS and RS of 84.6% and 89.7%. In multivariate analysis, only age and risk group achieved statistical significance for observed survival. GIST patients had an increased risk of second cancer with a hazard ratio of 2.47. CONCLUSIONS: This population-based study shows a spectrum of mutations in the c-KIT and PDGFR genes in GIST patients similar to that previously published. The OS and RS of GIST with the exon 18 PDGFR gene mutation could indicate that this subgroup of patients may be less aggressive and have a good prognosis, although less sensitive to treatment at recurrence. In our study, GIST patients have an increased risk of developing a second neoplasm.

Recent changes in breast cancer incidence in Spain, 1980-2004.

BACKGROUND: Since 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. METHODS: Cases 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. RESULTS: A 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). CONCLUSIONS: The recent downturn in breast cancer incidence among Spanish women older than 45 years is best explained by a period effect linked to screening saturation.

Identification of a novel pathogenic mutation in BRCA2 in a Spanish breast-ovarian cancer family.

Germline mutations in the BRCA1/2 genes contribute to most of inherited breast and ovarian cancers. We analyzed a family fulfilling classical criteria of hereditary breast/ovarian cancer. After complete sequencing of coding regions and splice junctions of both genes, a nonpreviously reported mutation in BRCA2 was detected in the index case. Direct mutation detection was performed with their relatives, and three of them were also mutation carriers, two healthy males and a patient afflicted with borderline ovarian cancer. The c.2999delCT, consists of a deletion of two bases in exon 11, in the limits of the ovarian cancer cluster region. This is a frameshift mutation that causes a disruption of the translational reading frame resulting in a stop codon 10 amino acids downstream in the 934 position of the BRCA2 protein, causing a truncation protein. This often causes a loss of function in the protein as critical parts of the amino acid chain are no longer created. Because of it, this mutation must be classified as pathogenic and can be regarded as the cause of the cancers in this family.

Cancer incidence in AIDS patients in Catalonia, Spain.

HIV infected people and AIDS patients develop cancer more frequently than the general population. The objective of this study was to evaluate the risk of developing cancer among 15 to 69 year old AIDS patients from two geographic areas: Tarragona and Girona provinces, in north-eastern Spain. We have studied invasive and in situ cancers (for all sites) among 1659 AIDS patients from +/-5 years around the date of their AIDS diagnosis by matching the population-based Cancer Registries with the AIDS Registry covering these populations. The periods used in the linkage were 1981-1998 for Tarragona and 1994-1999 for Girona. Sex and age-standardised incidence ratios (SIRs) of observed-to-expected cancers were calculated by type of cancer as a measure of risk. For selected types of cancers, SIRs were also calculated for HIV exposure category. Compared with the general population, incidence of cancer among AIDS patients (invasive and in situ) increased 22.9 fold in men (n=142) and 21.0 fold in women (n=45). High statistically significant SIRs were found for Kaposi's sarcoma (KS) (male, 486.4; female, 1030.0), non-Hodgkin's lymphoma (NHL) (male, 126.1; female, 192.8) and invasive cervical cancer (41.8). High risks were also found for Hodgkin's lymphoma (31.1), liver cancer (29.4) and lung cancer (9.4) in men, and in situ cervical cancer (24.4) in women. For all non-AIDS defining malignant neoplasms as a group SIRs were 3.4 in men and 2.5 in women. Among men, homo/bisexuality was strongly related to risk of KS and NHL. The rates of cervical cancer, Hodgkin's lymphoma, liver cancer and lung cancer were among the highest ever reported linked to HIV infection. For the cervical cancer this could be attributable to the low incidence of this cancer in the general population and to the high prevalence of intravenous drug users among HIV women and probably due to poor preventive strategies in this population.

Cosmetic outcome of breast conservative treatment for early stage breast cancer

Purpose. To evaluate the cosmetic outcome of breastconservative therapy and to examine the degree ofagreement between the patients’ and oncologists’ratings. We also analyze the influence of severalfactors on cosmesis.Methods and materials.We retrospectively evaluated145 patients with primary breast cancer treatedby local excision and radiotherapy between January2000 and May 2001. Cosmetic outcome wasevaluated by doctors and patients and was scoredas excellent, good, fair or poor.Results. 73% of patients rated cosmesis as excellentor good while the percentage was 71% when ratedby radiation oncologists. The degree of cosmesisconcordance evaluated by oncologists and patientswas low (kappa = 0.3). In our study the variableswhich significantly influence on the cosmetic outcomewere concomitant adjuvant chemotherapy(p = 0.04) and radiation therapy boost, either byelectron beam or brachytherapy (p = 0.013).Conclusion. The cosmetic outcome of breast conservingtherapy was good. There was a similar ratingby the patient and radiation oncologist, but thelevel of concordance between patients and doctorswas low. Factors that significantly influence thecosmesis appear to be concomitant adjuvant chemotherapyand radiation therapy boost

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[Time trend of breast cancer incidence in Catalonia]. / Incidencia del cáncer de mama en Cataluña: análisis de la tendencia.

BACKGROUND AND OBJECTIVE: Time trend of breast cancer incidence in Catalonia in the last 20 years is evaluated by a age-period-cohort model. POPULATION AND METHOD: Women older than 25 years diagnosed with breast cancer between 1980 and 1999 in the population covered by Tarragona and Girona population-based cancer registries. To investigate the age, period and birth cohort effect in the time trends of breast cancer incidence, Decarli and La Vecchia and Holdford's methods were used. RESULTS: The world age-standardized rate (25 to > or = 85 years old) has increased from 53.9 cases per 100,000 women-year in the period 1980-1984 to 83.9 per 100,000 women-year in the period 1995-1999. The annual percentage change was 2.2% (95% confidence interval, 1.8-2.6). According to age-period-cohort model an increment of the incidence exists depending on age and birth cohort, being the period effect less important. CONCLUSIONS: Breast cancer incidence has significantly increased in Catalonia. The birth cohort seems to be more important than the period effect in this increment, which supposes a change on the prevalence of the risk factor, although the use of screening diagnosis techniques might explain a part of the period effect.

Incidencia del cáncer de mama en Cataluña: análisis de la tendencia / Time trend of breast cancer incidence in Catalonia

Fundamento y objetivo: Se analiza la incidencia del cáncer de mama en Cataluña en estos últimos 20 años llevando a cabo un análisis de edad, período y cohorte. Población y método: Casos de cáncer de mama diagnosticados en mujeres de más de 25 años de edad entre 1980 y 1999 en la población cubierta por los registros de cáncer de Tarragona y Girona. Para investigar el efecto de la edad, el período y la cohorte de nacimiento en la incidencia se utilizaron los modelos de edad, período y cohorte propuestos por Decarli y La Vechia y el método de Holdford. Resultados: La tasa de incidencia (en mujeres de entre 25 y >= 85 años), ajustada por edad a la población estándar mundial, ha pasado de 53,9 nuevos casos por 105 en el período 1980-1984 a 83,9 por 105 en el período 1995-1999. El porcentaje de incremento anual fue del 2,2% (intervalo de confianza del 95%, 1,8-2,6). Según el modelo de edad, período y cohorte, existe un incremento de la incidencia en función de la edad y la cohorte de nacimiento, siendo menos importante el efecto del período. Conclusiones: La incidencia del cáncer de mama ha aumentado significativamente en Cataluña. En este aumento, el efecto cohorte es más importante que el efecto período, lo que indica un cambio en la prevalencia de los factores de riesgo, aunque el mayor empleo de las técnicas de diagnóstico precoz, como la mamografía, explicaría en parte el efecto período encontrado

Background and objective: Time trend of breast cancer incidence in Catalonia in the last 20 years is evaluated by a age-period-cohort model. Population and method: Women older than 25 years diagnosed with breast cancer between 1980 and 1999 in the population covered by Tarragona and Girona population-based cancer registries. To investigate the age, period and birth cohort effect in the time trends of breast cancer incidence, Decarli and La Vecchia and Holdford's methods were used. Results: The world age-standardized rate (25 to >= 85 years old) has increased from 53.9 cases per 100,000 women-year in the period 1980-1984 to 83.9 per 100,000 women-year in the period 1995-1999. The annual percentage change was 2.2% (95% confidence interval, 1.8-2.6). According to age-period-cohort model an increment of the incidence exists depending on age and birth cohort, being the period effect less important. Conclusions: Breast cancer incidence has significantly increased in Catalonia. The birth cohort seems to be more important than the period effect in this increment, which supposes a change on the prevalence of the risk factor, although the use of screening diagnosis techniques might explain a part of the period effect

[Probability of developing and dying of cancer in Catalonia during the period 1998-2001]. / Probabilidad de desarrollar y morir por cáncer en Cataluña en el período 1998-2001.

BACKGROUND AND OBJECTIVE: We intended to estimate the probability of developing and dying from cancer in Catalonia during the period 1998-2001. PATIENTS AND METHOD: We used a Bayesian model which incorporates data from the Tarragona and Girona Cancer Registries and from the Catalonia Mortality Registry. The probability of developing and dying from cancer has been calculated using a competitive risk-based methodology. RESULTS: Lifetime probability of developing cancer in Catalonia is almost 1 out of 2 (43.7%) for men and 1 out of 3 (32.1%) in women. The probability of dying from cancer is 29.1% for men and 17.9% in women. 67% of men and 56% of women diagnosed with cancer will die from this disease. One out of 14 men will develop a lung cancer during his life and 1 out of 11 women will develop breast cancer. CONCLUSIONS: The observed rising in the probability of developing cancer in Catalonia over the last ten years highlights even more than ever the importance of this health problem.

Probabilidad de desarrollar y morir por cáncer en Cataluña en el período 1998-2001 / Probability of developing and diying of cancer in Catalonia during the period 1998-2001

Fundamento y objetivo: Estimar la probabilidad de desarrollar y morir por cáncer en Cataluña durante el período 1998-2001. Pacientes y método: La incidencia en Cataluña se ha estimado mediante un modelo bayesiano que incorpora los datos de los Registros de Cáncer de Tarragona y Girona y los del Registro de Mortalidad de Cataluña. La probabilidad de desarrollar y morir por cáncer se ha calculado mediante una metodología basada en riesgos competitivos. Resultados: La probabilidad, a lo largo de la vida, de desarrollar un cáncer en Cataluña es casi 1 de cada 2 en los varones (43,7%) y 1 de cada 3 en las mujeres (32,1%). La probabilidad de morir por cáncer es del 29,1% en los varones y del 17,9% en las mujeres. Un 67% de los varones enfermos de cáncer y un 56% de las mujeres morirán a causa de esta enfermedad. Uno de cada 14 varones desarrollará un cáncer de pulmón durante su vida, y 1 de cada 11 mujeres uno de mama. Conclusiones: El aumento en la probabilidad de desarrollar cáncer en Cataluña observado en la última década resalta aún más la importancia de este problema de salud

Background and objective: We intended to estimate the probability of developing and dying from cancer in Catalonia during the period 1998-2001 Patients and method: We used a Bayesian model which incorporates data from the Tarragona and Girona Cancer Registries and from the Catalonia Mortality Registry. The probability of developing and dying from cancer has been calculated using a competitive risk-based methodology. Results: Lifetime probability of developing cancer in Catalonia is almost 1 out of 2 (43.7%) for men and 1 out of 3 (32.1%) in women. The probability of dying from cancer is 29.1% for men and 17.9% in women. 67% of men and 56% of women diagnosed with cancer will die from this disease. One out of 14 men will develop a lung cancer during his life and 1 out of 11 women will develop breast cancer. Conclusions: The observed rising in the probability of developing cancer in Catalonia over the last ten years highlights even more than ever the importance of this health problem

Early onset hereditary papillary renal carcinoma: germline missense mutations in the tyrosine kinase domain of the met proto-oncogene.

PURPOSE: Hereditary papillary renal carcinoma (HPRC) is characterized by a predisposition to multiple, bilateral papillary type 1 renal tumors caused by inherited activating missense mutations in the tyrosine kinase domain of the MET proto-oncogene. In the current study we evaluated the clinical phenotype and germline MET mutation of 3 new HPRC families. We describe the early onset clinical features of HPRC. MATERIALS AND METHODS: We identified new HPRC families of Italian (family 177), Spanish (family 223) and Cuban (family 268) descent. We evaluated their clinical features, performed MET mutation analysis by denaturing high performance liquid chromatography and DNA sequencing, and estimated age dependent penetrance and survival using Kaplan-Meier analysis. We characterized renal tumors by histology and fluorescence in situ hybridization. RESULTS: Identical germline MET c.3522G --> A mutations (V1110I) were identified in families 177 and 268 but no evidence of a founder effect was found. Affected members of family 223 carried a germline c.3906G --> C.3522G --> A MET mutation (V1238I). Age dependent penetrance but not survival was significantly earlier for the c.3522G -->A mutation than for the c.3906G --> A mutation in these HPRC families. Trisomy of chromosome 7 and papillary renal carcinoma type 1 histology were detected in papillary renal tumors. CONCLUSIONS: 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.

Time trends in incidence and mortality for chronic liver disease and liver cancer in the interval 1980-1997 in Catalonia, Spain.

BACKGROUND AND AIMS: It has been reported that the incidence of liver cancer and intrahepatic bile duct tumours might be increasing in some developed countries. The purpose of this study was to examine time trends of incidence and mortality rates of liver cirrhosis and liver cancer for the period 1980-1997 in Catalonia, Spain. METHODS: Data were obtained from the Catalan Mortality Registry and the Tarragona Cancer Registry. Joinpoint analysis was used to detect time-related changes in incidence and mortality of liver diseases. The cohort effect on mortality and incidence rates was explored by an age-period-cohort model. RESULTS: Mortality from liver cirrhosis decreased during the study period for both sexes and all age groups, with the exception of men aged between 25 and 35 years. No changes in incidence or mortality rates were observed for liver cancer. Mortality rates for intrahepatic bile duct tumours increased in men and women, while incidence rates remained stable. CONCLUSIONS: This study identified in Catalonia an increase in mortality due to liver cirrhosis among 25-35-year-old men. Mortality rates for intrahepatic bile duct tumours increased for all age groups and both sexes. The former could be related to hepatitis C or B viruses and human immunodeficiency virus co-infection, while the latter remains unexplained.