Mediterranean dietary pattern is associated with lower incidence of premenopausal breast cancer in the Seguimiento Universidad de Navarra (SUN) Project.

OBJECTIVE: Due to the growing interest in the role of dietary patterns (DPs) on chronic diseases, we assessed the association between a posteriori identified DPs in the Seguimiento Universidad de Navarra (SUN) Project - a prospective cohort study in a Mediterranean country - and breast cancer (BC) risk. DESIGN: DPs were ascertained through a principal component analysis based on 31 predefined food groups. BC cases were initially identified through self-report or, if deceased, from death certificates or by notification by the next kin. Women reporting BC were asked to provide a copy of their medical report and diagnoses for confirmation purposes. We fitted Cox regression models to assess the association between adherence to the identified DPs and BC risk. SETTING: Spanish university graduates. PARTICIPANTS: We included 10 713 young and middle-aged - mainly premenopausal - women. RESULTS: After a median follow-up of 10·3 years, we identified 100 confirmed and 168 probable incident BC cases. We described two major DPs: 'Western dietary pattern' (WDP) and 'Mediterranean dietary pattern' (MDP). A higher adherence to a WDP was associated with an increased risk of overall BC (multivariable-adjusted HR for confirmed BC Q4 v. Q1 1·70; 95 % CI 0·93, 3·12; P for trend = 0·045). Contrarily, adherence to a MDP was inversely associated with premenopausal BC (multivariable-adjusted HR Q4 v. Q1 0·33; 95 % CI 0·12, 0·91). No significant associations were observed for postmenopausal BC. CONCLUSIONS: Whereas a higher adherence to the WDP may increase the risk of BC, a higher adherence to the MDP may decrease the risk of premenopausal BC.

Trends in mortality from cutaneous malignant melanoma in Spain (1982-2016): sex-specific age-cohort-period effects.

BACKGROUND: Mortality from malignant cutaneous melanoma increased alarmingly during the second half of the 20th century in Spain and other European countries. OBJECTIVE: The aim was to analyse sex- and age-specific trends in melanoma mortality in Spain in the period 1982-2016. METHODS: European age-standardized melanoma mortality rates during the period 1982-2016 were calculated from mortality figures provided by the National Statistics Institute. Joinpoint regressions were used to identify significant points of change in trends and to compute average annual per cent change (AAPC). Age-cohort-period models were fitted to explore the effect of these variables on mortality. RESULTS: During the period 1982-2016, age-standardized melanoma mortality rates increased in Spain from 0.90 to 1.80 deaths per 100 000 people in men and from 0.64 to 1.11 per 100 000 in women, rising noticeably from 1982 to 1995 in both sexes and in all age groups. From the mid-90s different trends were observed depending on sex and age: there was a decrease in mortality in the population younger than 45 years (AAPC -2 in both sexes) and aged 45-64 years (AAPC -1 among men and -0.2 among women), but in the group over 64 years rates continued to increase (AAPC 1.7 and 0.2, respectively, for men and women). The mortality sex ratio decreased in the younger population but increased in older individuals. A cohort effect was observed with lower mortality in the cohorts born after 1943 in men and 1956 in women. There was also a period effect with decreased mortality rates at the beginning of the 1990s. CONCLUSIONS: Melanoma mortality rates in Spain increased during the last decades of the 20th century; however, later they stabilized in women and began to decrease in younger cohorts and middle-aged men. Promotion of primary and secondary prevention measures should continue, with particular emphasis on males over 65 years.

Spanish Mediterranean diet and other dietary patterns and breast cancer risk: case-control EpiGEICAM study.

BACKGROUND: Although there are solid findings regarding the detrimental effect of alcohol consumption, the existing evidence on the effect of other dietary factors on breast cancer (BC) risk is inconclusive. This study aimed to evaluate the association between dietary patterns and risk of BC in Spanish women, stratifying by menopausal status and tumour subtype, and to compare the results with those of Alternate Healthy Index (AHEI) and Alternate Mediterranean Diet Score (aMED). METHODS: We recruited 1017 incident BC cases and 1017 matched healthy controls of similar age (±5 years) without a history of BC. The association between 'a priori' and 'a posteriori' developed dietary patterns and BC in general and according to menopausal status and intrinsic tumour subtypes (ER+/PR+ and HER2-; HER2+; and ER-/PR- and HER2-) was evaluated using logistic and multinomial regression models. RESULTS: Adherence to the Western dietary pattern was related to higher risk of BC (OR for the top vs the bottom quartile 1.46 (95% CI 1.06-2.01)), especially in premenopausal women (OR=1.75; 95% CI 1.14-2.67). In contrast, the Mediterranean pattern was related to a lower risk (OR for the top quartile vs the bottom quartile 0.56 (95% CI 0.40-0.79)). Although the deleterious effect of the Western pattern was similarly observed in all tumour subtypes, the protective effect of our Mediterranean pattern was stronger for triple-negative tumours (OR=0.32; 95% CI 0.15-0.66 and Pheterogeneity=0.04). No association was found between adherence to the Prudent pattern and BC risk. The associations between 'a priori' indices and BC risk were less marked (OR for the top vs the bottom quartile of AHEI=0.69; 95% CI 0.51-0.94 and aMED=0.74; 95% CI 0.46-1.18)). CONCLUSIONS: Our results confirm the harmful effect of a Western diet on BC risk, and add new evidence on the benefits of a diet rich in fruits, vegetables, legumes, oily fish and vegetable oils for preventing all BC subtypes, and particularly triple-negative tumours.

Association of breast cancer and obesity in a homogeneous population from Spain.

OBJECTIVE: To evaluate for the first time in Spain if the association between obesity and breast cancer prognosis is similar to that reported in other countries with non Mediterranean dietary patterns. METHODS: Weight and height and other variables of interest, tumor characteristics and current clinical status 3 yr after diagnosis were retrieved from medical files of breast cancer women diagnosed during 2006. A total of 159 cases with complete information were studied and categorized according to the World Health Organization criteria in normal-/under-weight, overweight, and obese. RESULTS: Among breast cancer patients, 70.4% were classified as overweight/ obese and 29.6% as normal weight. Prevalence of obesity was high (38.4%) in comparison with information reported for healthy women of the same region (27.11%) and was higher among post-menopausal patients and in women with low level of alcohol and tobacco consumption. Moreover, overweight/ obese cases (79.5%) tended to have more often human epidermal growth factor receptor 2 status negative when compared with those with normal weight (70.2%; p=0.097) and the survival curves tended to be influenced by body mass index although without statistical significance. CONCLUSIONS: Overweight/obesity in a Mediterranean country is highly prevalent among breast cancer patients. Our results support a putative influence of obesity per se and not the alimentary patterns as a prognostic factor in breast cancer patients justifying the need to perform larger prospective studies.

Vitamin D3 levels in women and factors contributing to explain metabolic variations.

The elucidated metabolism of vitamin D3 in humans has been the support to explain the high involvement of this liposoluble vitamin in physiological functions. Clinical studies have associated levels of vitamin D3 metabolites with several disorders. Despite this knowledge, there is a controversy regarding the estimation of deficiency and the physiological and supraphysiological levels of vitamin D3 metabolites. The association between serum concentrations of vitamin D3 metabolites and several potentially influential factors (namely, age and anthropometric, seasonal, spatial and metabolic factors) is analyzed in this study. For this purpose, 558 women were recruited and interviewed in several Spanish provinces before blood sampling. Serum vitamin D3 and its metabolites were determined using an SPE-LC-MS/MS platform. The concentration range for vitamin D3 was 1.7-21.1 nmol/L and was influenced by body mass index (BMI), waist-to-hip ratio (WHR) and seasonal period. 25-hydroxyvitamin D3 levels were within 4.8-147.2 nmol/L and were related to WHR, season, latitude and calcium intake. The range of 24,25-dihydroxyvitamin D3, 0.3-15.0 nmol/L, was associated to BMI, WHR, season, latitude and calcium intake. Finally, energy intake influenced the vitamin D 25-hydroxylase through the 25-hydroxyvitamin D3/vitamin D3 ratio, which regulates the synthesis of the circulating form. According to these results, it is worth emphasizing the relevance of all these factors to explain the variability in serum levels of vitamin D3 and its metabolites. All these factors should be considered in future studies assessing the alteration of vitamin D3 metabolism.

Social mobility and healthy behaviours from a gender perspective in the Spanish multicase-control study (MCC-Spain).

There is evidence for the influence of socioeconomic status (SES) on healthy behaviours but the effect of social mobility (SM) is not yet well known. This study aims to analyse the influence of origin and destination SES (O-SES and D-SES) and SM on healthy behaviours and co-occurrence, from an integrated gender and age perspective. Data were obtained from the controls of MCC-Spain between 2008-2013 (3,606 participants). Healthy behaviours considered: healthy diet, moderate alcohol consumption, non-smoking and physical activity. SM was categorized as stable high, upward, stable medium, downward or stable low. Binary and multinomial logistic regression models were adjusted. Those aged <65, with a low O-SES, D-SES and stable low SM are less likely to have healthy behaviours in the case of both women (physically active: OR = 0.65 CI = 0.45-0.94, OR = 0.71 CI = 0.52-0.98, OR = 0.61 CI = 0.41-0.91) and men (non-smokers: OR = 0.44 CI = 0.26-0.76, OR = 0.54 CI = 0.35-0.83, OR = 0.41 CI 0.24-0.72; physically active: OR = 0.57 CI = 0.35-0.92, OR = 0.64 CI = 0.44-0.95, OR = 0.53 CI = 0.23-0.87). However, for those aged ≥65, this probability is higher in women with a low O-SES and D-SES (non-smoker: OR = 8.09 CI = 4.18-15.67, OR = 4.14 CI = 2.28-7.52; moderate alcohol consumption: OR = 3.00 CI = 1.45-6.24, OR = 2.83 CI = 1.49-5.37) and in men with a stable low SM (physically active: OR = 1.52 CI = 1.02-1.26). In the case of men, the same behaviour pattern is observed in those with a low O-SES as those with upward mobility, with a higher probability of co-occurring behaviours (three-to-four behaviours: OR = 2.00 CI = 1.22-3.29; OR = 3.13 CI = 1.31-7.48). The relationship of O-SES, D-SES and SM with healthy behaviours is complex and differs according to age and gender.

Breast cancer incidence in Spain before, during and after the implementation of screening programmes.

BACKGROUND: A downturn in breast cancer (BC) incidence among Spanish women has been recently reported and attributed to screening saturation. This article analyses BC trends and their relationship with the introduction of the screening programme in all Spanish regions having available information. MATERIAL AND METHODS: The study covers the period 1980-2004. All Spanish population-based cancer registries with 10 years of uninterrupted registration furnished data on invasive BC. Trends in BC incidence among women aged <45 years and among those aged > or =45 years were assessed using Poisson transition models to estimate the existence of a change-point in the overall trend. Furthermore, in those regions that had registered BC incidence before implementing the screening programme, the annual percentage change in women aged > or =45 years was computed before screening, during the first round of screening and after full coverage had been achieved. RESULTS: The study included 82 699 incident cases. Whereas BC increased during the 1980s and 1990s, from 2001 onwards a decline was observed among women aged > or =45 years. This phenomenon was clearly visible in regions that had implemented BC screening before 2000 and attained high participation rates. In such areas, BC incidence rose sharply during screening implementation, with an overall increase of approximately 20%-30%. BC incidence fell once full coverage was achieved and tended to level off or even increase thereafter, as was the case in Navarre. In women aged <45 years, BC increased by 1.7% per annum across the period. CONCLUSIONS: Screening has strongly influenced recent BC trends among Spanish women aged > or =45 years. Our results support the influence of screening saturation on the recent decline of BC. Among younger women, incidence is still rising, probably reflecting the lifestyle changes observed in younger generations.

Attenuation of the epidemic increase in non-Hodgkin's lymphomas in Spain.

BACKGROUND: Attenuation of the epidemic increase in non-Hodgkin's lymphoma (NHL) incidence has recently been reported in the USA and Nordic European countries. After two decades of steadily increasing NHL, this study sought to ascertain whether a similar stabilisation might have taken place in Spain in recent years. PATIENTS AND METHODS: NHL cases were drawn from 13 population-based Spanish cancer registries with a record of at least 10 years of uninterrupted registration during the period 1975-2004. 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. RESULTS: A total of 21 335 NHL cases (11 531 male and 9804 female) were identified. Although overall age- and registry-adjusted incidence rates rose by 5.74% annually among men and 6.58% among women across the period 1975-95, a statistically significant change-point was nevertheless detected in both sexes in 1996, followed by stabilisation. CONCLUSIONS: In Spain, NHL incidence levelled off in 1996 after a sharp increase during the 1970s and 1980s. This stabilisation is, partially at least, linked to the decrease in incidence of AIDS-related lymphomas among young adults.

Cancer mortality trends in Spain: 1980-2007.

INTRODUCTION: Since the 1990s, there has been a downturn in mortality for specific types of tumour in Spain and other European countries. This article reports on the current situation of cancer mortality in Spain, as well as mortality trends over the period 1980-2007, and provides an overview of cancer mortality trends in Europe in recent years. METHODS: Data were sourced from the National Statistics Institute (Instituto Nacional de Estadística - INE) and the World Health Organization mortality database. Mortality trends were studied using change-point Poisson regression models. RESULTS: All-cancer mortality decreased in both sexes from 1980 to 2007, owing to the fact that the tumours responsible for the highest number of deaths registered declining trends from the mid-1990s onwards. In men, mortality due to stomach and prostate cancer fell by >3% per annum in the last 10 years of the study period. In women, the largest contributions to the fall in cancer mortality were due to breast and colorectal cancers. In contrast, female mortality due to smoking-related cancers rose significantly. Within the European context, Spain's estimated 2005 mortality rates were intermediate for men and low for women. CONCLUSION: Cancer control is progressing in the right direction in Spain. Further interventions directed to reduce tobacco-related cancer mortality remain a priority, particularly for women.

Exercise and cancer: a position statement from the Spanish Society of Medical Oncology.

Due to improvements in the number of cancer survivors and survival time, there is a growing interest in healthy behaviors, such as physical activity (PA), and their potential impact on cancer- and non-cancer-related morbidity in individuals with cancer. Commissioned by the Spanish Society of Medical Oncology (SEOM), in this review, we sought to distill the most recent evidence on this topic, focusing on the mechanisms that underpin the effects of PA on cancer, the role of PA in cancer prevention and in the prognosis of cancer and practical recommendations for clinicians regarding PA counseling. Despite the available information, the introduction of exercise programs into the global management of cancer patients remains a challenge with several areas of uncertainty. Among others, the most effective behavioral interventions to achieve long-term changes in a patient's lifestyle and the optimal intensity and duration of PA should be defined with more precision in future studies.

Compositional analysis of dietary patterns.

Instead of looking at individual nutrients or foods, dietary pattern analysis has emerged as a promising approach to examine the relationship between diet and health outcomes. Despite dietary patterns being compositional (i.e. usually a higher intake of some foods implies that less of other foods are being consumed), compositional data analysis has not yet been applied in this setting. We describe three compositional data analysis approaches (compositional principal component analysis, balances and principal balances) that enable the extraction of dietary patterns by using control subjects from the Spanish multicase-control (MCC-Spain) study. In particular, principal balances overcome the limitations of purely data-driven or investigator-driven methods and present dietary patterns as trade-offs between eating more of some foods and less of others.

Molecular heterogeneity in chronic lymphocytic leukemia is dependent on BCR signaling: clinical correlation.

Chronic lymphocytic leukemia (CLL), the most frequent form of adult leukemia in Western countries, is characterized by a highly variable clinical course. Expression profiling of a series of 160 CLL patients allowed interrogating the genes presumably playing a role in pathogenesis, relating the expression of functionally relevant signatures with the time to treatment. First, we identified genes relevant to the biology and prognosis of CLL to build a CLL disease-specific oligonucleotide microarray. Second, we hybridized a training series on the CLL-specific chip, generating a biology-based predictive model. Finally, this model was validated in a new CLL series. Clinical variability in CLL is related with the expression of two gene clusters, associated with B-cell receptor (BCR) signaling and mitogen-activated protein kinase (MAPK) activation, including nuclear factor-kappaB1 (NF-kappaB1). The expression of these clusters identifies three risk-score groups with treatment-free survival probabilities at 5 years of 83, 50 and 17%. This molecular predictor can be applied to early clinical stages of CLL. This signature is related to immunoglobulin variable region somatic hypermutation and surrogate markers. There is a molecular heterogeneity in CLL, dependent on the expression of genes defining BCR and MAPK/NF-kappaB clusters, which can be used to predict time to treatment in early clinical stages.

The small variant of the apoptosis-associated X-chromosome RBM10 gene is co-expressed with caspase-3 in breast cancer.

BACKGROUND: There are very few studies on the final triggers of apoptosis, the caspases, in breast cancer. MATERIALS AND METHODS: Caspase-3 expression was studied by means of reverse transcript polymerase chain reaction (RT-PCR) in a series of 108 previously untreated patients with breast cancer. Expression levels were correlated with those obtained using the same technique of the apoptosis-associated X-chromosome genes RBMX, RBM3, RBM10 small and RBM10 large variant; Bcl-2 and Bax; the angiogenesis-associated genes VEGF and CD105 (endoglin); hMAM and Nup88. The correlation with the expression of hormone receptors, c-erb-B2, mutant p53 and Ki-67, all measured by means of immunohistochemistry, was also studied, as well as that with standard clinical parameters such as histological type, tumor size, axillary metastasis and DNA-ploidy. RESULTS: The only statistically significant correlations observed between caspase-3 mRNA expression and the parameters tested were a direct one with both the Bax (p = 0.007) and the small variant of the X-chromosome RBM10 gene (p = 0.018), and an inverse one with the angiogenesis-associated CD105 (endoglin) gene (p = 0.044). CONCLUSION: These results indicate that very few genes are involved in the last steps of the apoptotic cascade in breast cancer, among them one of the X-chromosome RBM family. They also support the relatively unexplored link between apoptosis and angiogenesis.

Identification of genes involved in imatinib resistance in CML: a gene-expression profiling approach.

The use of the tyrosine kinase inhibitor imatinib, which blocks the enzymatic action of the BCR-ABL fusion protein, has represented a critical advance in chronic myeloid leukemia (CML) treatment. However, a subset of patients initially fails to respond to this treatment. Use of complementary DNA (cDNA) microarray expression profiling allows the identification of genes whose expression is associated with imatinib resistance. Thirty-two CML bone marrow samples, collected before imatinib treatment, were hybridized to a cDNA microarray containing 6500 cancer genes, and analyzed using bootstrap statistics. Patients refractory to interferon-alpha treatment were evaluated for cytogenetic and molecular responses for a minimum of 12 months. A set of 46 genes was differentially expressed in imatinib responders and non-responders. This set includes genes involved in cell adhesion (TNC and SCAM-1), drug metabolism (cyclooxygenase 1), protein tyrosine kinases and phosphatases (BTK and PTPN22). A six-gene prediction model was constructed, which was capable of distinguishing cytogenetic response with an accuracy of 80%. This study identifies a set of genes that may be involved in primary resistance to imatinib, suggesting BCR-ABL-independent mechanisms.

A haplotype containing the p53 polymorphisms Ins16bp and Arg72Pro modifies cancer risk in BRCA2 mutation carriers.

Germline mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of developing breast and other cancers; however, remarkable differences exist regarding disease manifestation in mutation carriers. It has been suggested that other genetic and/or environmental factors modify not only the appearance but also the age of onset and type of tumor in BRCA1/2-associated cases. The aim of the present study was to investigate the role of two p53 polymorphisms (c.97-147ins16bp and c.215c>g, p.Arg72Pro) as potential modifiers. For this purpose we investigated the possible association between the two polymorphisms and disease status in 447 BRCA1/2 mutation carriers belonging to 170 Spanish breast and/or ovarian cancer families. Genotype and haplotype analyses revealed that the presence of a specific haplotype carrying the allele without the 16-bp insertion and the variant allele for the Arg72Pro (No Ins-72Pro haplotype) was associated with an earlier age of onset in BRCA2 mutation carriers. We found an increased risk of developing a first primary tumor (breast or ovarian) before 35 years of age for individuals who carried at least one No Ins-72Pro haplotype (OR: 2.69; 95% CI: 1.15-6.29; P=0.022). We confirmed these data by a functional study in which we compared different p53 genotypes in relation to their apoptotic response after cell treatment with a cytotoxic drug (AraC). Our results revealed a decrease in p53 apoptotic rate associated with the No Ins-72Pro haplotype.

Epidemiological characteristics of a Spanish cohort of patients diagnosed with squamous cell carcinoma of head and neck: distribution of risk factors by tumor location.

PURPOSE: Head and neck cancer is a highly heterogeneous disease comprising a large number of tumors located in the cervicofacial area. This study aimed to determine the epidemiological characteristics of squamous-cell carcinomas of the head and neck in the Spanish population, and the distribution of risk factors based on tumor locations. METHODS/PATIENTS: A cohort of 459 patients (75 oral cavity, 167 oro-/hypopharyngeal and 217 laryngeal cancers) recruited in 19 hospitals participating in the Spanish head and neck cancer cooperative group were included over 3 years (2012-2014). Epidemiological parameters and risk factors were obtained from a self-administered questionnaire, and tumor characteristics were obtained from clinical records. Multivariate multinomial logistic regression was used to assess factors associated with tumor location. RESULTS: Most patients were males (88.4 %), smokers (95 %) and drinkers (76.5 %). Relative to laryngeal cancer, pharyngeal cancer and oral cancer were more common in women than men (OR 3.58, p = 0.003 and 4.33, p = 0.001, respectively); pharyngeal cancer was more associated with rural environment (OR 1.81, p = 0.007) and weekly alcohol intake (10-140 g: OR 2.53, p = 0.012; 141-280 g: OR 2.47, p = 0.023; >280 g: OR 3.20, p = 0.001) and less associated with pack-years of smoking (21-40 packs: OR 0.46, p = 0.045; 41-70 packs: OR 0.43, p = 0.023; ≥71 packs: OR 3.20, p = 0.015). CONCLUSIONS: The distribution of these tumors differs between the sexes, with a higher proportion of oral cavity and pharyngeal tumors in women than in men. Oro-/hypopharyngeal cancers were more strongly associated with rural areas and with alcohol consumption, although less strongly associated with smoking than laryngeal tumors.

Municipal pleural cancer mortality in Spain.

BACKGROUND: Pleural cancer is a recognised indicator of exposure to asbestos and mesothelioma mortality. AIMS: To investigate the distribution of municipal mortality due to this tumour, using the autoregressive spatial model proposed by Besag, York, and Mollie. METHODS: It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardised mortality ratios, smoothed relative risk (RR) estimates, and the distribution of the posterior probability that RR >1. RESULTS: There was a higher risk of death due to pleural cancer in well defined towns and areas, many of which correspond to municipalities where asbestos using industries once existed for many years, the prime example being the municipal pattern registered for Barcelona Province. The quality of mortality data, the suitability of the model used, and the usefulness of municipal atlases for environmental surveillance are discussed.

Levels and predictors of persistent organic pollutants in an adult population from four Spanish regions.

This research aimed to assess serum concentrations of a group of persistent organic pollutants (POPs) in a sample of adults recruited in four different regions from Spain and to assess socio-demographic, dietary, and lifestyle predictors of the exposure. The study population comprised 312 healthy adults selected from among controls recruited in the MCC-Spain multicase-control study. Study variables were collected using standardized questionnaires, and pollutants were analyzed by means of gas chromatography with electron capture detection. Multivariable analyses were performed to identify predictors of log-transformed pollutant concentrations, using combined backward and forward stepwise multiple linear regression models. Detection rates ranged from 89.1% (hexachlorobenzene, HCB) to 93.6% (Polychlorinated biphenyl-153 [PCB-153]); p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) showed the highest median concentrations (1.04ng/ml), while HCB showed the lowest (0.24ng/ml). In the multivariable models, age was positively associated with HCB, p,p'-DDE, and PCB-180. BMI was associated positively with p,p'-DDE but negatively with PCB-138. Total accumulated time residing in an urban area was positively associated with PCB-153 concentrations. The women showed higher HCB and lower p,p'-DDE concentrations versus the men. Notably, POP exposure in our study population was inversely associated with the breastfeeding received by participants and with the number of pregnancies of their mothers but was not related to the participants' history of breastfeeding their children or parity. Smoking was negatively associated with HCB and PCB-153 concentrations. Consumption of fatty foods, including blue fish, was in general positively associated with POP levels. Although POP environmental levels are declining worldwide, there is a need for the continuous monitoring of human exposure in the general population. The results of the present study confirm previous findings and point to novel predictors of long-term exposure to persistent organic pollutants.

Elevated mammaglobin (h-MAM) expression in breast cancer is associated with clinical and biological features defining a less aggressive tumour phenotype.

BACKGROUND: Mammaglobin (h-MAM) is expressed mainly by breast epithelial cells, and this feature has been used to detect circulating breast cancer cells and occult metastases in sentinel axillary lymph nodes of breast cancer patients. However, the biological role of mammaglobin is completely unknown. METHODS: We studied 128 fresh-frozen breast cancer specimens by means of reverse transcriptase-polymerase chain reaction and quantified their h-MAM mRNA expression. This was then correlated with histological and nuclear grade, oestrogen and progesterone receptor expression, c-erb-B2 and mutant p53 expression, as well as with cellular proliferation measured by means of the Ki67 labelling index, DNA ploidy and S-phase, and finally with the presence or not of invaded axillary nodes in the mastectomy specimen. RESULTS: In the univariate analysis, high h-MAM expression (above the median for the whole group) correlated significantly (P < 0.05) with oestrogen and progesterone receptor expression, diploid DNA content, low Ki67 labelling index, low nuclear grade and almost significantly (P = 0.058) with the absence of axillary nodal invasion in the mastectomy specimen. In a final, multivariate model, only progesterone receptor expression, diploid DNA content and absence of nodal invasion were found to be independently associated with high h-MAM expression. CONCLUSION: All of the features associated with mammaglobin expression reflect, without exception, a less aggressive tumour phenotype. Further studies are needed to clarify whether this is attributable to h-MAM expression itself, or to another mechanism of which mammaglobin expression forms part.

Mortality trends in cutaneous malignant melanoma in Spain, 1967-1986.

The effect of age, cohort, and year of death on the mortality of cutaneous malignant melanoma is determined by the use of a Poisson log-linear model. During the period of the study, mortality due to this tumor increased exponentially (an annual rise of 11% in both sexes). The model attributes this rise to a cohort effect. The relative risk for the 1952 cohort as compared to the 1892 cohort is 530 for men and 280 for women. In the younger generations, no signs of leveling off are to be seen. The sharp increase in mortality due to malignant melanoma of the skin has also been witnessed in other countries and suggests a real increase in incidence. One explanation for this epidemic phenomenon lies in the progressive rise in exposure to UV radiation.