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Biomedical subjects

J Estève

Publications and source records attributed to J Estève.

At least 37 records · Page 2Linked to original sources

Sex- and strain-specific induction of renal tumors by ochratoxin A in rats correlates with DNA adduction.

Ochratoxin A (OTA), a nephrotoxic and carcinogenic mycotoxin, has been implicated as an etiologic agent in the Balkan endemic nephropathy (BEN), a chronic disease affecting populations in the Balkans. Compared with unaffected individuals, patients suffering from BEN and/or urinary tract tumors were more frequently found to have a capacity for rapid debrisoquine (DB) metabolism, a metabolic reaction related mostly to cytochrome P450 (CYP) 2D in humans. Earlier studies, using female DA and Lewis rats phenotyped as poor or extensive DB metabolizers respectively, revealed a parallelism between DB-4 hydroxylation and OTA-4 hydroxylation. To investigate whether genetic polymorphism modifies tumor induction, we have compared both OTA-induced renal carcinogenicity and DNA adducts in DA and Lewis rats of both sexes. OTA induced renal adenocarcinoma, DA male rats being most responsive, while DA females were resistant. Lewis rats showed an intermediate renal tumor response. OTA also induced malignant transitional cell carcinomas of the bladder in DA male rats only. DNA adducts in the kidney, as judged by the nature of spots and prevalence in OTA-treated animals, were significantly correlated with renal carcinogenicity of OTA, being highest in DA males and lowest in DA females. A parallelism between karyomegalies and tumors of the kidney was observed. In conclusion, our results classify OTA as a genotoxic carcinogen in rats, with sex-specific response controlled in part by drug-metabolizing enzymes that convert OTA into reactive intermediates.

Animals↗

Survival of patients with oesophageal and gastric cancers in Europe. EUROCARE Working Group.

The EUROCARE study is a European Union project to collect survival data from population-based cancer registries and analyse them according to standardised procedures. We investigated and compared oesophageal and gastric cancer survival in 17 countries between 1985 and 1989. Time trends in survival over the 1978-1989 period were also investigated in 13 countries. The overall European 1-year relative survival rates were 33% for oesophageal cancer and 40% for gastric cancer. The corresponding 5-year relative survival rates were 10 and 21%, respectively. Important intercountry survival differences exist within Europe for oesophageal and gastric cancer. Taking the European average as the reference, the relative risk (RR) of death at 5 years was at least 30% higher in Denmark, Poland, Estonia and Slovenia for oesophageal cancer and in Denmark, England, Scotland and Poland for gastric cancer. In the other countries survival figures were close to the European average. Gender had little influence on survival, whilst age at diagnosis was inversely related to prognosis. There was a slight improvement between 1978 and 1989 in 5-year overall relative survival rates for both oesophageal cancer (RR = 0.80, 95% confidence interval (CI) 0.72-0.90) and gastric cancer (RR = 0.88, 95% CI 0.82-0.94). Differences in quality of care and stage at diagnosis can explain in part the differences in survival found in the EUROCARE countries. Significant improvement in prognosis has still to be achieved.

Adolescent↗

Survival of patients with primary liver cancer, pancreatic cancer and biliary tract cancer in Europe. EUROCARE Working Group.

The EUROCARE Study is a European Union project to assemble survival data from population-based cancer registries and analyse them according to standard procedures. We investigated and compared liver, pancreatic and biliary tract cancer survival in 17 countries from 1985 to 1989. Time trends in survival over the 1978-1989 period were also investigated in 12 countries. The overall European mean 1 year relative survival was 16% for primary liver cancer, 26% for biliary tract cancer and 15% for pancreatic cancer. The corresponding 5-year relative survival was 5, 12 and 4%, respectively. Taking the European average as the reference, the relative risk (RR) of death was at least 20% higher for the three cancers in Denmark and Estonia. Survival tended to be higher in Spain for primary liver cancer and biliary tract cancer. Gender had little influence on survival whilst age at diagnosis was inversely related to prognosis. There was an improvement in 1-year relative survival rate for primary liver cancer: relative risk (RR) of 0.68 (95% confidence interval (CI) of 0.60-0.77) for 1987-1989 versus 1978-1980 and biliary tract cancer (RR 0.77, 95% CI 0.68-0.87). There was less variation in 5-year relative survival rate over time. Some intercountry survival differences for primary liver, biliary tract and pancreatic cancers exist over Europe. Differences in quality of care, in particular treatment aggressiveness, may explain some of these differences in survival. New approaches to the management of these cancers need to be found.

Adolescent↗

Inducible nitric oxide synthase, anti-oxidant enzymes and Helicobacter pylori infection in gastritis and gastric precancerous lesions in humans.

Chronic inflammation induced by Helicobacter pylori infection has been associated with an increased risk of stomach cancer. We have analysed 167 stomach biopsies from 99 patients for H. pylori infection and immunohistochemically for the expression of inducible nitric oxide synthase (iNOS), catalase and superoxide dismutases (SODs) as markers of oxidative stress. Biopsies were graded as follows on the basis of histology: normal, superficial gastritis, variable severity of atrophic gastritis with or without intestinal metaplasia, and dysplasia. iNOS was detected in inflammatory cells in all types of gastritis with or without H. pylori infection and independently of its severity. In foveolar cells, iNOS was observed in approximately 25% of all biopsies showing any type of gastritis, but in a markedly higher proportion of dysplastic samples. Catalase and Mn-type SOD in inflammatory cells and catalase in foveolar cells were more frequently observed in marked atrophic gastritis biopsies than in less severe gastritis. Individual differences were found in the expression of these enzymes within groups with the same severity of gastritis. Prolonged oxidative stress in severe gastritis and dysplasia may play an important role in gastric carcinogenesis, through increased damage of DNA and tissue by reactive oxygen and nitrogen species.

Adult↗

Tumors associated with p53 germline mutations: a synopsis of 91 families.

Although inherited p53 mutations are present in all somatic cells, malignant transformation is limited to certain organs and target cells. The analysis of 475 tumors in 91 families with p53 germline mutations reported since 1990 shows that breast carcinomas are most frequent (24.0%), followed by bone sarcomas (12.6%), brain tumors (12.0%), and soft tissue sarcomas (11.6%). The sporadic counterparts of these tumors also carry a high incidence of p53 mutations, suggesting that in these tissues p53 mutations are capable of initiating the process of malignant transformation. Hematological neoplasms (acute lymphoblastic leukemia and Hodgkin's lymphoma) and adrenocortical carcinomas occurred at a frequency of 4.2 and 3.6%, respectively. One-half of the families fulfilled the diagnostic criteria of the Li-Fraumeni syndrome. There were marked organ-specific differences in the mean age at which carriers of p53 germline mutations present with neoplastic disease: 5 years for adrenocortical carcinomas, 16 years for sarcomas, 25 years for brain tumors, 37 years for breast cancer, and almost 50 years for lung cancer. Analysis of the mutational spectrum showed a predominance of G:C-->A:T transitions at CpG sites, suggesting an endogenous formation, eg, by deamination of 5-methylcytosine, rather than a causation by environmental mutagenic carcinogens. The location of mutations within the p53 gene was found to be similar to that of somatic mutations in sporadic tumors. There is no evidence of an organ or target cell specificity of p53 germline mutations; the occasional familial clustering of certain tumor types is more likely to reflect the genetic background of the respective kindred or the additional influence of environmental and nongenetic host factors.

Disease Susceptibility↗

Diet and cancers of the larynx and hypopharynx: the IARC multi-center study in southwestern Europe.

The main causes of cancer of the larynx and hypopharynx are smoking cigarettes and drinking alcohol. However, for these as well as for other cancers of the upper aerodigestive tract, some dietary components, mainly low consumption of fruit and vegetables, have been observed to be associated with increased cancer risk. We report results from a multicenter case-control study carried out in six regions of Europe located in northern Spain, northern Italy, Switzerland, and France. A total of 1,147 males with cancer (cases) and 3,057 population controls were interviewed on usual diet, lifelong drinking and smoking habits, and occupational history. Cancer cases had histologically verified epidermoid carcinomas. The cancers were classified in two anatomic sub-entities: the epilarynx (hypopharynx and upper part of the larynx), which enters into contact with the bolus and the air; and the endolarynx, through which air and tobacco smoke pass, but not the bolus. A previous report from this study found that alcohol drinking presents a greater risk factor for cancer of the epilarynx than for cancer of the endolarynx. The main results regarding diet indicate that high intake of fruit, vegetables, vegetable oil, fish, and low intake of butter and preserved meats were associated with reduced risk of both epilaryngeal and endolaryngeal cancers, after adjustment for alcohol, tobacco, socioeconomic status, and non-alcohol energy intake. Among nutrients, a reduced risk was found for high intake of vitamins C and E and for a high polyunsaturated/saturated fatty acids (P/S) ratio. While these variables are relevant in scoring nutritional behaviour, it remains unresolved whether the biologic properties of these nutrients play a role in the apparent protective effect.

Alcohol Drinking↗

Nutrition and laryngeal cancer.

The main etiologic factors of cancers of the larynx and hypopharynx are alcohol and tobacco, and their prevalence in different populations explains, to a large extent, the wide variations in incidence observed around the world. Besides these two main risk factors, however, diet also seems to play a role in determining the risk of these cancers. There is consistent evidence that low consumption of fruit and vegetables is associated with higher risk, after statistical adjustment for alcohol and tobacco. Consumption of vegetable oils and fish and a moderately high polyunsaturated/saturated fatty acid ratio (P/S ratio) were reported to be associated with reduced risk. Low intake of vitamin C, beta-carotene and vitamin E were reported consistently to be associated with higher laryngeal cancer risk, but there was no clear evidence that these micronutrients are better predictors of cancer risk than the principal food groups from which their intake levels were estimated, i.e., fruits, vegetables, vegetable oils, and fish. Given the overwhelming role of tobacco and alcohol in the etiology of these cancers and the extremely low incidence among nonsmokers/nondrinkers, the available studies provide no estimate of the role of diet in subjects not exposed to these factors. The evidence indicates, however, that, in the presence of tobacco and/or alcohol, low intake of fruit and vegetables may account for 25 to 50 percent of the cases among men.

Alcohol Drinking↗

Multiple primary cancers and estimation of the incidence rates and trends.

The use of different registration rules from one registry to another, both generally and also for paired organs, leads to variations in the proportion of multiple primary cancers: in men, from 0.4 to 4.9% for the colon, 0.1 to 2.7% for the lung, and 4.1 to 8.6% for the mouth and pharynx. Subjective factors, often impossible to verify, contribute to these variations. The impact on the estimation of incidence rates and trends is not negligible for cancers of the mouth and the pharynx and for all the cancers taken together. The trend towards an increase of cancers of the mouth and pharynx in the Bas-Rhin disappeared when the incidence was expressed taking only the first cancer (incidence by individual) into consideration, and the differences in incidence between the Calvados and the Bas-Rhin registries for the same site also disappeared. In the absence of harmonisation of the rules and methods followed for registration, incidence by individual is the only approach which makes it possible to compare incidence rates and trends between registries.

Breast Neoplasms↗

Is neuroblastoma screening evaluation needed and feasible?

Despite the five million children who have been screened for neuroblastoma in Japan through detection of catecholamine metabolites, it is still uncertain whether screening for this disease is beneficial. The Japanese study has clearly indicated that screening at 6 months or earlier leads to heavy overdiagnosis. It is shown in this paper that screening at a later age may give the same reduction in mortality with possibly less overdiagnosis. However, it is estimated that, even with two screens at 12 and 18 months, the reduction in mortality would not greatly exceed 25%, under realistic hypotheses on the length of the preclinical phase of the disease. The evaluation of the efficacy of this screening strategy would need the recruitment of half a million children per year over 5-7 years and the follow-up of an equal number of controls. Such a trial would improve our knowledge of the natural history of the disease and might help to answer some questions raised recently regarding its biological heterogeneity.

Age Factors↗

Estimating the accuracy of dietary questionnaire assessments: validation in terms of structural equation models.

The validity and precision of questionnaire assessments of the habitual intake of individuals are usually evaluated by comparison with reference measurements that are supposed to provide a best possible substitute for the individuals' true intake values. In the present paper, a measurement error model is presented, defining different types of error--random or systematic, and within or between individuals--that may occur in dietary intake measurements. It is then discussed how simple latent variable models (structural equation models) can be used to estimate the average magnitude of these various types of error. So far, approaches described for the analysis of dietary validity studies have all been based on the assumption that the random errors of repeat reference measurements, taken by the same method on different occasions, are uncorrelated, so that the average of a sufficiently large number of repeat reference measurements will provide an accurate ranking of individuals by true intake level. In the present paper it is described how, by additional comparison with a third type of measurement such as a biochemical marker, the validity of dietary questionnaire measurements can be evaluated even in situations where the random errors of repeat reference measurements can no longer be assumed to be independent.

Ascorbic Acid↗

Adjustment for bias due to errors in exposure assessments in multicenter cohort studies on diet and cancer: a calibration approach.

An advantage of multicenter cohort studies on diet and cancer is that these may include populations over a wide range of dietary exposure. With some simplifying assumptions, the information from such multicenter studies may be divided into 1) estimated relationships within each of the separate cohorts, between individual-level measurements of dietary exposure and disease outcome, and 2) an estimated between-cohort relationship, between the mean intake measurements and mean incidence rates. Errors in the dietary exposure measurements may lead to different amounts of bias in each of these estimated relationships, in particular when dietary questionnaire methods cannot easily be standardized. A calibration approach can be used to adjust for such differences in bias. This will improve the relative weighting of within- and between-cohort components of evidence for a diet-disease association.

Cohort Studies↗

Trends in cancer incidence and mortality.

Time trends in cancer risk have often been summarised by the observation that mortality from cancers associated with tobacco is increasing rapidly, while mortality from all other cancers is either stable or falling slightly, this slight decline being dominated by the decrease in mortality from stomach cancer. Until recently, and with some variation between the sexes, this simple summary of cancer mortality trends would have been broadly correct for a number of developed countries, and it remains useful in dismissing claims of an impending and unexplained epidemic of cancer, but it does not apply to all countries, and in some there have recently been striking changes in the trends in mortality from cancers associated with tobacco. Cancer mortality has been widely accepted as the most important measure of progress against cancer, since it reflects the impact of cancer on people, and has been considered less subject to distortion than incidence or survival, although this is open to question. Cancer mortality also reflects trends in incidence and survival to a greater or lesser extent. There has been controversy, however, over how cancer mortality trends should be interpreted, as well as over which measures should be used to assess progress in cancer control. An overall summary of trends in mortality from all cancers combined is of limited value in assessing progress against cancer, in any case. Increases in a common lethal cancer may numerically dominate overall mortality trends, perhaps concealing declines in less common or less lethal cancers, while opposite trends in cancers of the lung and stomach, for example, might lead to an overall impression that little has changed. Further, up to a third of cancer patients will not die of cancer, and cancer mortality statistics do not reflect their experience at all. Cancer mortality trends only indirectly reflect trends in the number of people who are diagnosed with cancer in a given year, and those who do die of cancer in a given year may have been diagnosed more than 3 years previously, even though many die earlier: this blurs the responsiveness of routine cancer mortality statistics as a measure of recent progress, and alternative measures have been proposed. Trends in competing risks of death, especially at higher ages, may also complicate the interpretation of cancer mortality trends. The chance of developing cancer, and in that event, the chances of surviving it, are of direct interest to individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Detecting spatial autocorrelation of cancer risk when population density is heterogeneous].

Several studies have shown that cancer incidence and cancer mortality are spatially autocorrelated. Implicit to the demonstration of this characteristic is the assumption of similar variability of risk estimates in all geographic units. As this assumption is often incorrect in the context of most geographical studies of cancer incidence and mortality, we propose a simulation method which takes into account the heterogeneity of population density to study the distributions of the Moran I and Smans D statistics under the correct hypothesis. The results are compared with the classical approach using incidence data from the "Département" of Isère.

Female↗

Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies.

BACKGROUND: Colorectal cancer is a major public health problem in both North America and western Europe, and incidence and mortality rates are rapidly increasing in many previously low-risk countries. It has been hypothesized that increased intakes of fiber, vitamin C, and beta carotene could decrease the risk of colorectal cancer. PURPOSE: The objective of this study was to examine the effects of fiber, vitamin C, and beta-carotene intakes on colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. The study was designed to estimate risks in the pooled data, to test the consistency of the associations across the studies, and to examine interactions of the effects of the nutrients with cancer site, sex, and age. METHODS: Original data records for 5287 case subjects with colorectal cancer and 10,470 control subjects without disease were combined. Logistic regression analysis was used to estimate relative risks and confidence intervals for intakes of fiber, vitamin C, and beta carotene, with the effects of study, sex, and age group being adjusted by stratification. RESULTS: Risk decreased as fiber intake increased; relative risks were 0.79, 0.69, 0.63, and 0.53 for the four highest quintiles of intake compared with the lowest quintile (trend, P < .0001). The inverse association with fiber is seen in 12 of the 13 studies and is similar in magnitude for left- and right-sided colon and rectal cancers, for men and for women, and for different age groups. In contrast, after adjustment for fiber intake, only weak inverse associations are seen for the intakes of vitamin C and beta carotene. CONCLUSION: This analysis provides substantive evidence that intake of fiber-rich foods is inversely related to risk of cancers of both the colon and rectum. IMPLICATIONS: If causality is assumed, we estimate that risk of colorectal cancer in the U.S. population could be reduced about 31% (50,000 cases annually) by an average increase in fiber intake from food sources of about 13 g/d, corresponding to an average increase of about 70%.

Adolescent↗