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N Malats

Publications and source records attributed to N Malats.

At least 19 recordsLinked to original sources

Gender-related differences in clinical and pathological characteristics and therapy of bladder cancer.

OBJECTIVE: To confirm the very high male:female ratios previously observed among Spanish bladder cancer patients and to assess gender differences in tumoral characteristics, diagnostic procedures, and treatment in a large series of consecutive bladder cancer patients. PATIENTS AND METHODS: All newly diagnosed bladder cancer patients (n=615) in 17 Spanish hospitals, between 1997-2000, were included. Information was collected both through personal interviews to patients and from medical records using a structured form. RESULTS: Seventy-six percent of tumours were superficial. The male:female ratio was 6.7 and it was similar for superficial and infiltrating tumours. Women were older than men at the diagnosis of bladder cancer (68.2+/-9.4 years versus 65.7+/-9.7 years, p=0.01). Ten percent of superficial tumours in women, versus 3% in men, were classified as "other histological types" (p=0.008). T1GIII tumours were more frequent among men (17% versus 7%, p=0.047). On the other hand, women were more likely to present with 0a-stage tumours (48.6% versus 35.5%, p=0.04), multiple tumours (50% versus 29%, trend test: 0.005), multi-centric tumours (54% versus 38%, p=0.019), and larger infiltrating masses (5.2 cm versus 3.8 cm, p=0.03) than men. Among 0a-stage tumours, only 23% of women compared to 54% of men received transurethral resection (TUR) alone (p=0.002). Women were almost five-fold more likely to receive additional therapies to TUR (p=0.004) after adjusting for age, geographical area, stage, tumoral size, nuclear grade, and multiplicity. CONCLUSION: The study confirms the very high male:female ratio of bladder cancer in Spain. We found substantial differences in the pathological characteristics of tumours from men and women. There was a tendency for women to receive more frequently non-standard, more aggressive, therapy than men.

Adult↗

Meta-analysis of studies on individual consumption of chlorinated drinking water and bladder cancer.

STUDY OBJECTIVE: To evaluate whether consumption of chlorinated drinking water is associated with bladder cancer. DESIGN: A bibliographic search was conducted and the authors selected studies evaluating individual consumption of chlorinated drinking water and bladder cancer. The authors extracted from each study risk estimates for intermediate and long term (>40 years) consumption of chlorinated water, stratified by sex when possible, and performed meta-analysis for the two exposure levels. A meta-analysis was also performed of the dose-response regression slopes. SETTING: Populations in Europe and North America. PARTICIPANTS: Those included in six case-control studies (6084 incident bladder cancer cases, 10,816 controls) and two cohort studies (124 incident bladder cancer cases) fulfilling the inclusion criteria. MAIN RESULTS: Ever consumption of chlorinated drinking water was associated with an increased risk of bladder cancer in men (combined OR=1.4, 95%CI 1.1 to 1.9) and women (combined OR=1.2, 95%CI 0.7 to 1.8). The combined OR for mid-term exposure in both genders was 1.1 (95% CI 1.0 to 1.2) and for long term exposure was 1.4 (95%CI 1.2 to 1.7). The combined estimate of the slope for a linear increase in risk was 1.13 (95% CI 1.08 to 1.20) for 20 years and 1.27 (95% CI 1.15 to 1.43) for 40 years of exposure in both sexes. CONCLUSIONS: This meta-analysis of the best available epidemiological evidence indicates that long term consumption of chlorinated drinking water is associated with bladder cancer, particularly in men. The observed relative risk is only moderately high, but the population attributable risk could be important as the vast majority of the population of industrialised countries is potentially exposed to chlorination byproducts for long time periods.

Chlorine↗

Basic glossary on genetic epidemiology.

This is the second of a series of three glossaries on genetic concepts used in epidemiological research that the journal is publishing with the objective of helping the reader "walk" around the journal.

Humans↗

Advanced glossary on genetic epidemiology.

This is the last of a series of glossaries on terms used in genetic epidemiology published by the journal. This glossary covers the most advanced genetic terms, most of which are related to new study designs and laboratory techniques. It provides the reader with examples and references of real studies that applied each of the study designs defined in the glossary. This should help the reader grasp the subtleties of each of these strategies and will allow the reader to research the literature according to their interest.

Epidemiology↗

Family history of cancer and germline BRCA2 mutations in sporadic exocrine pancreatic cancer.

BACKGROUND: Hereditary factors have been reported in 5-10% of cases with exocrine pancreatic cancer and recent data support a role for BRCA2. AIMS: We have studied the prevalence of germline BRCA2 mutations in two groups of patients with exocrine pancreatic cancer from an unselected series in Spain: group A included 24 cases showing familial aggregation of cancer and group B included 54 age, sex, and hospital matched cases without such evidence. METHODS: Information was obtained by interview of patients and was validated by a telephone interview with a structured questionnaire. In patients from group A, >80% of the coding sequence of BRCA2 was analysed; in patients from group B, the regions in which germline BRCA2 mutations have been described to be associated with pancreatic cancer were screened. RESULTS: Telephone interviews led to reclassification of 7/54 cases (13%). Familial aggregation of cancer was found in 24/165 cases (14.5%); six patients had a first degree relative with pancreatic cancer (3.6%) and nine patients had relatives with breast cancer. Germline BRCA2 mutations were not identified in any patient from group A (0/23). Among group B cases, one germline variant (T5868G>Asn1880Lys) was found in a 59 year old male without a family history of cancer. The 6174delT mutation was not found in any of the 71 cases analysed. CONCLUSIONS: The overall prevalence of BRCA2 mutations among patients with pancreatic cancer in Spain is low and the 6174delT mutation appears to be very infrequent. Our data do not support screening patients with cancer of the pancreas for germline BRCA2 mutations to identify relatives at high risk of developing this tumour.

Adult↗

Cystic fibrosis transmembrane regulator (CFTR) DeltaF508 mutation and 5T allele in patients with chronic pancreatitis and exocrine pancreatic cancer. PANKRAS II Study Group.

BACKGROUND: An increased risk of chronic pancreatitis has been described among carriers of the cystic fibrosis transmembrane regulator (CFTR) mutation. In addition, patients with cystic fibrosis may have a higher risk of exocrine pancreatic cancer. AIMS: To determine the prevalence of the DeltaF508 mutation and 5T allele, the most common CFTR disease related variants, and to assess their association with lifestyle factors in an unselected series of patients with chronic pancreatitis or pancreatic cancer. SUBJECTS: Patients recruited to the multicentre PANKRAS II study with a diagnosis of chronic pancreatitis and pancreatic cancer from whom normal DNA was available. METHODS: The DeltaF508 mutation and 5T allele were analysed using polymerase chain reaction amplified normal DNA. Information on clinical and lifestyle factors was obtained through personal interviews. RESULTS: Among patients with pancreatitis, no DeltaF508 alleles were found and the prevalence of the 5T allele was 10.5%, similar to that described in the general population. Among patients with pancreatic cancer, the prevalence of the DeltaF508 mutation and the 5T allele was 2.4% and 5.5%, respectively. 5T allele carriers with cancer consumed significantly less alcohol than non-carriers (p=0.038). CONCLUSIONS: Our findings do not support the view that the DeltaF508 mutation and 5T allele confer a higher risk of chronic pancreatitis or pancreatic cancer. Nevertheless, our data suggest that interactions between CFTR polymorphism and environmental factors may play a role in the pathogenesis of these diseases. Our study emphasises the need for a multinational study to conclusively establish the role of CFTR variants as genetic susceptibility factors for chronic pancreatitis and pancreatic cancer.

Adenocarcinoma↗

Gene-environment interactions in pancreatic cancer.

Exocrine pancreatic cancer remains a major cause of cancer death in Western populations. Despite many efforts, little is known about its etiology. Tobacco is the only established cause, although the proportion of cases of exocrine pancreatic cancer attributed to it is only 30%. A family history of pancreatic cancer accounts for 10% of the cases of this disease. A large proportion of cases are due to yet unrecognized factors. The combined contribution of genetic susceptibility and environmental factors has rarely been considered. A higher risk of exocrine pancreatic cancer has been observed for patients with hereditary pancreatitis who smoked. It has also been suggested that CFTR mutations and alcohol could interact in the development of exocrine pancreatic cancer. Common variants in a large number of genes could act as low-penetrance alleles. Little is known about their role as susceptibility markers for exocrine pancreatic cancer, except for metabolic enzymes. A few studies have assessed the association between polymorphisms in these genes and exocrine pancreatic cancer. Surprisingly, none of them observed an interaction with tobacco consumption. The reality may be more complex; exocrine pancreatic cancer is genetically heterogeneous and it could involve many somatic and heritable mutations. Gene-gene interactions and endogenous factors, among others, can contribute to tumor development. Future epidemiological studies should consider all of these aspects together.

Environment↗

Validity of the hospital discharge diagnosis in epidemiologic studies of biliopancreatic pathology. PANKRAS II Study Group.

BACKGROUND: The aim was to analyse the magnitude, direction and predictors of change in the main hospital discharge diagnosis (HDD) after a clinical expert review, among patients included in a multicentre molecular epidemiologic study of biliopancreatic diseases. METHODS: A total of 602 patients with a suspicion diagnosis of pancreas cancer (PC), cancer of the extrahepatic biliary system (CEBS) or benign biliopancreatic pathologies (BPP) were prospectively recruited at five general hospitals. A structured form was used to collect information from medical records. A panel of experts revised all diagnostic information and established the main clinicopathological diagnosis (CPD) by consensus. RESULTS: Of the 204 cases with a HDD of PC, 176 (86%) were deemed to have a CPD of PC, eight of CEBS, twelve a neoplasm of different origin, four BPP and four syndromic diagnoses. Thus, 28 cases (14%) were false positives. Of the 129 patients with a HDD of CEBS, 15 (12%) were false positives. Nine of the 396 cases with a HDD of non-PC (2%) had a CPD of PC (false negatives), whilst 14 of 471 patients with a HDD of non-CEBS (3%) were deemed to have CEBS. Overall, sensitivity and specificity of HDD for PC were, respectively, 95 and 93%, and for CEBS, 89 and 97%. Cytohistological confirmation and laparotomy were independent predictors of diagnostic change. CONCLUSIONS: Validity of the HDD was high, but its association with some clinical variables suggests that sole reliance on HDD can significantly bias results, and highlights the need to review all HDDs. Alternatively, only patients at high risk of misdiagnosis could be reviewed: primarily, those lacking a cytohistological diagnosis or a laparotomy. No exclusions appear warranted solely on the basis of age, gender or tumour spread.

Aged↗

Occupation and pancreatic cancer in Spain: a case-control study based on job titles. PANKRAS II Study Group.

BACKGROUND: Occupational exposures may increase the risk of exocrine pancreatic cancer. This study aimed to identify occupations that in Spain may be associated with such risk. METHODS: Incident cases of pancreatic cancer and hospital controls were prospectively identified and interviewed during their hospital stay. Occupational history was obtained by direct interview with the patient and was available for 164 (89%) of 185 pancreatic cancer cases and for 238 (90%) of 264 controls. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. RESULTS: A significant increased odds ratio (OR) was observed in men for 'physical, chemistry and engineering science technicians'. Elevated risks were also found for 'metal moulders, sheet-metal workers, structural metal workers, welders and related workers', 'painters and varnishers' and 'machinery mechanics and fitters'. 'Agricultural workers' did not present an increased risk for pancreas cancer in men. In women, however, high OR were observed for 'agricultural workers' and for 'textile and garment workers'. Most associations remained unchanged after considering long duration of the exposure and the period 5-15 years before diagnosis. CONCLUSIONS: Few occupations were at increased risk for pancreatic cancer, and the associations observed are in accordance with previous studies. The increases in risk observed for women in agricultural and textile jobs, and for men in the manufacture of dyes and pigments may deserve further attention.

Acute Disease↗

Risk of pancreatic cancer and occupational exposures in Spain. PANKRAS II Study Group.

The objective of the study was to analyse the relationship between occupational exposures and risk of pancreatic cancer. Incident cases of pancreatic cancer and hospital controls were prospectively identified and interviewed during the hospital stay. Occupational history was obtained by direct interview with the patient, and was available for 164 (89%) of 185 pancreatic cancer cases, and 238 (90%) of 264 controls. Two industrial hygienists evaluated exposures to 22 suspected carcinogens previously associated with pancreatic cancer. Occupational exposures were also assessed using the Finnish job-exposure matrix (FINJEM). For each type of pesticide group, moderately increased odds ratios (OR) were apparent in the high-intensity category, highest for arsenical pesticides (OR=3.4; 95% CI 0.9-12.0), and 'other pesticides' (OR=3.17; 95% CI 1.1-9.2). ORs for aniline derivatives, and dyes and organic pigments, were also higher for high-intensity exposure, and increased when lagged and restricted to long duration of exposure. ORs above 3 were observed for the following agents evaluated by FINJEM: pesticides, benzo[a]pyrene, lead, volatile sulphur compounds, and sedentary work. Whilst generally negative, results lend moderate support to the hypothesis of an association between exposure to some pesticides and pancreatic cancer. Larger studies could address the potential for these compounds to modify the carcinogenic risk of other environmental exposures. Suggestive increases in risk from aniline derivatives, dyes and organic pigments, and benzo[a]pyrene may also deserve further attention.

Aged↗

Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism.

Glutathione S-transferase (GST) polymorphism may contribute to the individual variability in detoxifying lung carcinogens. This effect might be particularly relevant at low-level exposure to environmental carcinogens, such as in nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case-control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls from eight countries. Information on environmental exposures was obtained through a personal interview. The presence of GSTM1 and GSTT1 genes was determined using multiplex PCR. GSTM1-positive samples were then analyzed for *1A and *1B polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9-2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9-6.1) than for cases with adenocarcinomas. It was also elevated in individuals with long-term exposure to indoor wood combustion (OR, 3.1; 95% CI, 0.9-9.9), in subjects who mainly lived in a rural setting (OR, 3.6; 95% CI, 1.0-13), and in cases exposed to occupational carcinogens (OR, 10.7; 96% CI, 0.4-260) but not in subjects exposed to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in smokers. It does not seem to interact with ETS exposure, although we cannot exclude that it does in association with exposure to other specific environmental carcinogens.

Adenocarcinoma↗

Medical conditions in patients with pancreatic and biliary diseases: validity and agreement between data from questionnaires and medical records. PANKRAS II Study Group.

The aims of the study were to assess the agreement between data from personal interviews and medical records on selected medical conditions, to evaluate the validity of each source of information, and to estimate the prevalence of these conditions in pancreatobiliary pathology. Between 1992 and 1995, 602 patients with pancreatobiliary diseases were included in the PANKRAS II Study. Information from interview and medical records was available in 88% of cases. The agreement between both data sources was poor only for cholecystitis and mental disorders. The validity of both sources of information was high or acceptable for all conditions except for cholecystitis. Prevalence of past medical conditions was similar to that reported previously and varied according to diagnosis, gender, age, educational level, and hospital of admission. Research aimed at assessing the prevalence of less common diseases should consider subject- and health-related factors in collecting information.

Adolescent↗

Association between coffee drinking and K-ras mutations in exocrine pancreatic cancer. PANKRAS II Study Group.

STUDY OBJECTIVE: To analyse the relation between coffee consumption and mutations in the K-ras gene in exocrine pancreatic cancer. DESIGN: Case-case study. Consumption of coffee among cases with the activating mutation in the K-ras gene was compared with that of cases without the mutation. SETTING AND PATIENTS: All cases of pancreatic cancer newly diagnosed at five hospitals in Spain during three years were included in the PANKRAS II Study (n = 185, of whom 121 whose tissue was available for molecular analysis are the object of the present report). Over 88% were personally interviewed in hospital. DNA was amplified from paraffin wax embedded tissues, and mutations in codon 12 of K-ras were detected by the artificial RFLP technique. MAIN RESULTS: Mutations were found in tumours from 94 of 121 patients (77.7%). Mutations were more common among regular coffee drinkers than among non-regular coffee drinkers (82.0% v 55.6%, p = 0.018, n = 107). The odds ratio adjusted by age, sex, smoking and alcohol drinking was 5.41 (95% CI 1.64, 17.78). The weekly intake of coffee was significantly higher among patients with a mutated tumour (mean of 14.5 cups/week v 8.8 among patients with a wild type tumour, p < 0.05). With respect to non-regular coffee drinkers, the odds ratio of a mutated tumour adjusted by age, sex, smoking and alcohol drinking was 3.26 for drinkers of 2-7 cups/week, 5.77 for drinkers of 8-14 cups/week and 9.99 for drinkers of > or = 15 cups/week (p < 0.01, test for trend). CONCLUSIONS: Pancreatic cancer cases without activating mutations in the K-ras gene had drank significantly less coffee than cases with a mutation, with a significant dose response relation: the less they drank, the less likely their tumours were to harbour a mutation. In exocrine pancreatic cancer the K-ras gene may be activated less often among non-regular coffee drinkers than among regular drinkers. Caffeine, other coffee compounds or other factors with which coffee drinking is associated may modulate K-ras activation.

Adolescent↗