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N Malats

Publications and source records attributed to N Malats.

At least 37 records · Page 2Linked to original sources
PubMed1999

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↗
PubMed1999

Strategic issues in the design and interpretation of studies on metabolic polymorphisms and cancer.

This chapter describes in a simple way the most important issues of epidemiological design, with emphasis on studies on metabolic polymorphisms. Different options are offered to the researcher who approaches a molecular epidemiology study. Case-control studies and cohort studies have different and sometimes complementary advantages and disadvantages. The sources of bias and the choice of controls, with specific problems in the context of investigations on metabolic polymorphisms, are key issues. Confounding is an issue that needs further clarification in the field, partly because of the lack of complete biological knowledge on the complex relationships between exposure, markers of susceptibility, and cancer. Metabolic polymorphisms are correctly interpreted as effect modifiers of the exposure-disease relationship. This interpretation implies that studies should be planned in order to have sufficient statistical power and that an interactive term should be modelled in the statistical analysis.

Bias↗
PubMed1998

Learning from case reports: diagnostic issues in an epidemiologic study of pancreatic cancer.

Epidemiologic studies on exocrine pancreatic cancer show a large heterogeneity in diagnostic criteria applied to define "caseness." Reanalyses conducted after review of diagnostic information have yielded substantially different results than those based on more crude classifications of disease. During a multicenter prospective study on mutations in the K-ras gene in pancreatic and biliary diseases, hospital diagnoses from 602 patients were reviewed by a panel of experts. There were two main motivations to do so: a generic interest for the quality of the diagnostic data, and the anticipation that a firm diagnosis could be needed to assess whether patients whose tumors did not harbor the mutation were true negatives or false negatives. In addition, the review of diagnoses was helpful to minimize tissue misclassification, and it had a high educational value for clinicians and epidemiologists. This article illustrates why and how this was so through a brief presentation of the 10 most significant cases. With respect to selection and classification of subjects, the main issues that studies on pancreatic cancer need to address are the differential diagnosis of exocrine pancreatic cancer and pancreatitis, the differential diagnosis of exocrine pancreatic cancer and other abdominal tumors, and the use of survival as a hallmark of pancreatic cancer. In epidemiologic studies of pancreatic cancer, it is warranted that a panel of experts centrally reviews all the existing diagnostic evidence (cytohistological and other) of all patients, regardless of whether they have cytohistological confirmation and of their hospital discharge diagnosis.

Adenocarcinoma↗
PubMed1998

Emergency admission for cancer: a matter of survival?

The objective of this study was to compare the pre-hospital health care process, clinical characteristics at admission and survival of patients with a digestive tract cancer first admitted to hospital either electively or via the emergency department. The study involved cross-sectional analysis of information elicited through personal interview and prospective follow-up. The setting was a 450-bed public teaching hospital primarily serving a low-income area of Barcelona, Catalonia, Spain. Two hundred and forty-eight symptomatic patients were studied, who had cancer of the oesophagus (n = 31), stomach (n = 70), colon (n = 82) and rectum (n = 65). The main outcome measures were stage, type and intention of treatment and time elapsed from admission to surgery; the relative risk of death was calculated using Cox's regression. There were 161 (65%) patients admitted via the emergency department and 87 (35%) electively. The type of physician seen at the first pre-hospital visit had more often been a general practitioner in the emergency than in the elective group (89% vs 75%, P < 0.01). Emergency patients had seen a lower number of physicians from symptom onset until admission, but two-thirds had made repeated visits to a primary care physician. Emergency patients were less likely to have a localized tumour and a diagnosis of cancer at admission, and surgery as the initial treatment. Median survival was 30 months for elective patients and 8 months for emergency patients (P < 0.001), and the relative risk of death (RR) was 1.83 (95% confidence interval, CI, 1.32-2.54). After adjustment for strong prognostic factors, emergency patients continued to experience a significant excess risk (RR = 1.58; CI 1.10-2.27). In conclusion, in digestive tract cancers, admission to hospital via the emergency department is a clinically important marker of a poorer prognosis. Emergency departments can only partly counterbalance deficiencies in the effectiveness of and integration among the different levels of the health system.

Adult↗
PubMed1998

Occurrence, trends and environment etiology of pancreatic cancer.

This review summarizes data on the occurrence, the trends, and the life-style, environmental, occupational and genetic determinants of pancreatic cancer. Epidemiologic evidence implicates tobacco smoking as one cause. The evidence regarding alcohol consumption is inconsistent. Although both positive and inconclusive findings are encountered, the bulk of the evidence on coffee consumption is negative. Fat intake is linked with obesity and diabetes mellitus, which are risk factors for pancreatic cancer. Fruit and vegetable consumption appears to be protective. No occupational or environmental agent has been confirmed to increase the risk, but epidemiologic evidence is inconsistent, Little is known about the role of genetic polymorphisms of metabolic enzymes in pancreas carcinogenesis. Pancreatic cancer shows high rates of mutations of Ki-ras and losses or mutations of tumor suppressor genes (p53, p16INK4A, and SMAD4/DPC-4). Ki-ras mutations have been associated with life-style factors in relation to pancreatic cancer, but the evidence is still scant and inconsistent.

Female↗
PubMed1997

Ki-ras mutations in exocrine pancreatic cancer: association with clinico-pathological characteristics and with tobacco and alcohol consumption. PANK-ras I Project Investigators.

The aims of this study were (i) to assess the prevalence and spectrum of codon 12 Ki-ras mutations in patients diagnosed with exocrine pancreatic cancer (EPC) in 2 general hospitals between 1980 and 1990, (ii) to analyze the association of this genetic alteration with clinical and pathological characteristics, and (iii) to determine the association of Ki-ras mutations with tobacco and alcohol consumption. DNA was amplified from paraffin-embedded tissue samples and mutations in codon 12 of Ki-ras were detected using the artificial RFLP technique. Cox proportional-hazards regression and unconditional logistic regression were applied. Codon 12 Ki-ras mutations were detected in 30 of 51 cases for which molecular results were available. The amino-acid substitutions were Asp (8), Val (6), and Arg (3). A double mutation, including always a Val, was detected in 5 cases. None of the 4 nonductal pancreatic neoplasms were mutated. The mutation prevalence was 79% in metastases and 54% in primary tumors. The risk of a mutated tumor was 3 times higher in alcohol drinkers than in non-drinkers, and a linear trend was apparent. When age, gender, hospital, and tobacco and alcohol consumption were taken into account, a high risk for mutations was detected in patients who only smoked and in patients who only drank, but less so in patients who both smoked and drank. These results raise novel hypotheses regarding the role of tobacco and alcohol in EPC.

Adult↗
PubMed1997

Serum anti-p53 antibodies and prognosis of patients with small-cell lung cancer.

BACKGROUND: Some patients with cancer develop antibodies against the p53 tumor suppressor protein. The presence of these antibodies in serum has been associated with the expression of mutant p53 by the tumor and in some studies with a poorer survival. PURPOSE: The goals of this study were to determine the prevalence of anti-p53 antibodies in the serum of patients with newly diagnosed small-cell lung cancer (SCLC) and to assess the clinical relevance of the presence of these antibodies in the serum, particularly their relationship with tumor response to treatment and with patient survival. METHODS: In this prospective study, serum was obtained from 170 patients at the time of diagnosis of SCLC who were to subsequently receive platinum- or doxorubicin-based chemotherapy at any one of four hospitals in Barcelona, Spain, from October 1991 through June 1994. Normal human sera from blood bank donors (n = 50) served as controls. The presence of anti-p53 antibodies was determined by western blot analysis with the use of purified recombinant p53 protein. As of January 1996, 96.5% of the patients had been treated and observed in the study, for a median follow-up time of 33.5 months. Survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression and unconditional logistic regression analyses were conducted. All P values resulted from two-sided tests. RESULTS: Anti-p53 antibodies were detected in the serum of 27 (16%) of the 170 patients studied. None of 50 serum samples from normal individuals contained anti-p53 antibodies. Analysis of pretreatment clinical characteristics demonstrated that a weight loss of less than 5% (P = .025), a serum lactic acid dehydrogenase (LDH) level of less than 450 U/L (P = .002), and limited stage disease (i.e., tumor confined to one hemithorax, with local and regional lymph node positivity for tumor cells and/or ipsilateral pleural effusion allowed) (P < .001) were associated with a statistically significant complete response to therapy. The presence of serum anti-p53 antibodies was not associated with clinical characteristics, such as age (P = .622), functional status (P = 1.0), disease stage (P = .634), complete response to treatment (P = .572), and survival (P = .492) or with any laboratory parameters including known prognostic factors in SCLC, such as serum sodium or LDH concentration (P values of .731 and .246, respectively). CONCLUSIONS AND IMPLICATIONS: The presence of anti-p53 antibodies in the serum of patients with newly diagnosed SCLC was not associated with any clinical characteristics or prognostic markers, suggesting that, in this context, the measurement of anti-p53 antibodies is not a useful prognostic marker.

Aged↗
PubMed1997

Vegetable and fruit intake and the risk of lung cancer in women in Barcelona, Spain.

A case-control study on women was carried out in Barcelona, Spain, to investigate the relationship of lung cancer with the intake of vegetables, fruits and some foods of animal origin. The study included 103 cases and 206 controls matched by age and residence. Diet intake was assessed by means of a food frequency questionnaire. A reduction in risk, adjusted for smoking habit, was found for the intake of yellow/orange vegetables (mainly carrots) and tomatoes. The odds ratio (OR) and 95% confidence interval (CI) for the highest versus lowest tertile of intake were 0.37 (0.19-0.74) for yellow/orange vegetables and 0.45 (0.22-0.91) for tomatoes; both had a significant inverse trend. A tendency to a reduction in risk of lung cancer with increased intake was observed for all vegetables, leafy green vegetables, dark green vegetables and cruciferous, but these associations did not reach statistical significance. No association with lung cancer was found for the intake of fruits or foods of animal origin rich in retinol. Similar patterns were observed for women who never smoked and when the analysis was restricted to adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival.

PURPOSE: Anti-Hu antibodies (HuAb) recognize antigens expressed by neurons and small-cell lung cancer (SCLC). High titers of HuAb were initially reported in serum from patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) and SCLC. Preliminary studies have indicated that some SCLC patients without PEM/SN harbor low titer of HuAb in their serum, and that the SCLC of these patients may grow more indolently. Based on these observations, we conducted a multicenter prospective study of SCLC patients without PEM/SN to determine the incidence and prognostic implications of HuAb. METHODS: Serum samples were collected at diagnosis of SCLC in 196 patients without PEM/SN. HuAb were determined by immunoblot of purified recombinant HuD antigen. RESULTS: HuAb were detected in 32 (16%) of the 196 patients. Of the 170 patients who received treatment for the tumor, 27 (16%) were HuAb positive. HuAb was associated with limited disease stage (59.3% v 38.6%; P = .047), complete response to therapy (55.6% v 19.6%; P < .001), and longer survival (14.9 v 10.2 months; P = .018). In a logistic regression analysis, HuAb status was an independent predictor of complete response induction. The probability of achieving a complete response was more than five times higher in HuAb-positive than in HuAb-negative patients (odds ratio, 5.4; 95% confidence interval, 1.71 to 16.89; P = .004). Cox multivariate analysis indicated that HuAb status was not independently associated with survival. CONCLUSION: The presence of HuAb at diagnosis of SCLC is a strong and independent predictor of complete response to treatment. This feature accounts for the association between HuAb and longer survival.

Antibodies, Neoplasm↗
PubMed1996

Do we believe what patients say about their neoplastic symptoms? An analysis of factors that influence the interviewer's judgement.

In order to analyze factors that influence an interviewer's judgement of the validity of responses given by patients on the duration of their neoplastic signs and symptoms, 183 consecutive symptomatic patients hospitalized for a digestive tract neoplasm were personally interviewed. The validity of the answers was judged by the interviewers to be high in 156 cases (85%), and low in 27 (15%). The subjective validity of the interview (SVI) was inversely related to the time elapsed from first medical symptom to interview (TFMSI), even after adjusting for the duration of the interview (p < 0.05). SVI was not influenced by whether patient and interviewer agreed on the first symptom. SVI was inversely related to educational level (p < 0.01) and to occupational class (p = 0.04). Patients whose Karnofsky's Index (KI) was > or = 80 were over twice as likely to yield valid responses (TFMSI-adjusted odds ratio [OR] = 2.82, p = 0.037). Multivariate analyses selected education, TFMSI and KI as independent predictors of the interviewer assessment. The SVI of patients admitted to the hospital through the Emergency Department was lower than that of subjects whose admission was planned (OR = 6.49, p = 0.005). In this study SVI related in a logical manner to the characteristics of the interview, of the subjects and of their clinical course. It hence appeared to reasonably estimate the validity of data collected. Identifying factors that affect the reliability of patients' responses would help increase the validity of studies on the duration of cancer symptoms.

Aged↗
PubMed1996

Sex as a prognostic factor in gastric cancer.

The aim of this study was to assess whether survival of gastric cancer patients differed between males and females. Although it is well known that the incidence of gastric cancer is higher for men than for women, the existence of a sex-specific prognosis has seldom been addressed. Studies based on population registries have not assessed the role of stage and histology. Cases of histologically confirmed gastric carcinoma were obtained from three Spanish hospitals in Soria (n = 405), Barcelona (n = 249) and Mataró (n = 197). Differences in possible confounders were tested between men and women and survival analyses were performed separately by hospital. Cox's proportional hazards models were used to account for age, tumour stage, histology and tumour sub-location. Only in Mataró was a significant difference in the stage distribution observed between women and men, with a lower proportion of local stage tumours among women (P = 0.047). No statistically significant differences of histological type between men and women were observed in any of the centres. After adjusting for tumour stage and age, women were observed to have significantly better survival in Barcelona (female to male hazard ratio (HR) = 0.578, P < 0.001); this effect was marginal in Soria (HR = 0.788, P = 0.092) and non-significant in Matar-o (HR = 0.895, P = 0.54). Age-adjusted hazard ratios were calculated within each tumour stage. For Barcelona, the effect of better prognosis among women was most marked at local stage (HR = 0.320, P = 0.013), and in Soria at the regional stage (HR = 0.426, P = 0.002). Although in Mataró all HRs were below unity, none were statistically significant. Little effect was observed at the disseminated stage. The other covariables exerted no influence. Women appear to have a better prognosis than men, and the difference could be tumour stage dependent. Confirmation of these findings would give a valuable insight into gastric cancer growth and ultimately be of use in planning treatment.

Aged↗