Biomedical subjects

Marina Pollán

Publications and source records attributed to Marina Pollán.

At least 19 recordsLinked to original sources

PubMed2007

Oesophageal cancer mortality in Spain: a spatial analysis.

BACKGROUND: Oesophageal carcinoma is one of the most common cancers worldwide. Its incidence and mortality rates show a wide geographical variation at a world and regional level. Geographic mapping of age-standardized, cause-specific death rates at a municipal level could be a helpful and powerful tool for providing clues leading to a better understanding of its aetiology. METHODS: This study sought to describe the geographic distribution of oesophageal cancer mortality for Spain's 8077 towns, using the autoregressive spatial model proposed by Besag, York and Mollié. Maps were plotted, depicting standardised mortality ratios, smoothed relative risk (RR) estimates, and the spatial pattern of the posterior probability of RR being greater than 1. RESULTS: Important differences associated with area of residence were observed in risk of dying from oesophageal cancer in Spain during the study period (1989-1998). Among men, excess risk appeared across the north of the country, along a band spanning the length of the Cantabrian coastline, Navarre, the north of Castile & León and the north-west of La Rioja. Excess risk was likewise observed in the provinces of Cadiz and part of Seville in Andalusia, the islands of Tenerife and Gran Canaria, and some towns in the Barcelona and Gerona areas. Among women, there was a noteworthy absence of risk along the mid-section of the Cantabrian seaboard, and increases in mortality, not observed for men, in the west of Extremadura and south-east of Andalusia. CONCLUSION: These major gender- and area-related geographical differences in risk would seem to reflect differences in the prevalence of some well-established and modifiable risk factors, including smoking, alcohol consumption, obesity and diet. In addition, excess risks were in evidence for both sexes in some areas, possibly suggesting the implication of certain local environmental or socio-cultural factors. From a public health standpoint, small-area studies could be very useful for identifying locations where epidemiological research and intervention measures ought to receive priority, given the potential for reducing risk in certain places.

Adult↗

PubMed2006

Municipal mortality due to thyroid cancer in Spain.

BACKGROUND: Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. 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 standardized mortality ratios, smoothed relative risk (RR) estimates, and the posterior probability that RR > 1. RESULTS: From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna) and western areas of Asturias and Orense. CONCLUSION: The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor.

Bayes Theorem↗

PubMed2006

Positive correlation between the expression of X-chromosome RBM genes (RBMX, RBM3, RBM10) and the proapoptotic Bax gene in human breast cancer.

In a recent report, it has been postulated that the ubiquitous RBM proteins might constitute a novel family of apoptosis modulators. We measured the expression of the X-chromosome RBM genes (RBMX, RBM3, and RBM10) in 122 breast cancers by means of differential RT-PCR. Using the same method, we also studied the expression of the apoptosis-related genes Bcl-2 and Bax. Markers of hormone dependence (estrogen and progesterone receptors), proliferation (Ki67 and DNA-ploidy), angiogenesis (VEGF and CD105), as well as oncogene (c-erb-B2), and tumor suppressor gene (p53) expression were also analyzed. The expression of all X-chromosome RBM genes was significantly associated with the expression of the proapoptotic Bax gene (RBMX, P=0.039; RBM3, P<0.001; RBM10 large variant, P<0.001; RBM10 small variant, P<0.001). Furthermore, the expression of both RBM10 variants was significantly associated with the expression of the VEGF gene (large variant, P=0.004; small variant, P=0.003). We also found an association of borderline significance (P=0.05) between the expression of RBM3, the large variant of RBM10 and wild-type p53. Expression of the small RBM10 variant, finally, was associated with high proliferation of the tumors (Ki67>or=20%; P=0.037). The expression of both RBM10 variants seems to be interdependent to a significant degree (r=0.26, P=0.006). From these results, it seems that the X-chromosome, through its RBM genes, plays a formerly unknown role in the regulation of programmed cell death (apoptosis) in breast cancer.

Apoptosis↗

PubMed2006

Association between health information, use of protective devices and occurrence of acute health problems in the Prestige oil spill clean-up in Asturias and Cantabria (Spain): a cross-sectional study.

BACKGROUND: This paper examines the association between use of protective devices, frequency of acute health problems and health-protection information received by participants engaged in the Prestige oil spill clean-up in Asturias and Cantabria, Spain. METHODS: We studied 133 seamen, 135 bird cleaners, 266 volunteers and 265 paid workers selected by random sampling, stratified by type of worker and number of working days. Information was collected by telephone interview conducted in June 2003. The association of interest was summarized, using odds ratios (OR) obtained from logistic regression. RESULTS: Health-protection briefing was associated with use of protective devices and clothing. Uninformed subjects registered a significant excess risk of itchy eyes (OR:2.89; 95%CI:1.21-6.90), nausea/vomiting/dizziness (OR:2.25; 95%CI:1.17-4.32) and throat and respiratory problems (OR:2.30; 95%CI:1.15-4.61). There was a noteworthy significant excess risk of headaches (OR:3.86: 95%CI:1.74-8.54) and respiratory problems (OR:2.43; 95%CI:1.02-5.79) among uninformed paid workers. Seamen, the group most exposed to the fuel-oil, were the worst informed and registered the highest frequency of toxicological problems. CONCLUSION: Proper health-protection briefing was associated with greater use of protective devices and lower frequency of health problems. Among seamen, however, the results indicate poorer dissemination of information and the need of specific guidelines for removing fuel-oil at sea.

Acute Disease↗

PubMed2006

Occupational exposure to ionizing radiation and electromagnetic fields in relation to the risk of thyroid cancer in Sweden.

OBJECTIVES: This study sought to ascertain the risk of thyroid cancer in relation to occupational exposure to ionizing radiation and extremely low-frequency magnetic fields (ELFMF) in a cohort representative of Sweden's gainfully employed population. METHODS: A historical cohort of 2 992 166 gainfully employed Swedish male and female workers was followed up from 1971 through 1989. Exposure to ELFMF and ionizing radiation was assessed using three job exposure matrices based on industrial branch or occupational codes. Relative risks (RR) for male and female workers, adjusted for age and geographic area, were computed using log-linear Poisson models. RESULTS: Occupational ELFMF exposure showed no effect on the risk of thyroid cancer in the study. However, female workers exposed to high intensities of ionizing radiation registered a marked excess risk (RR 1.85, 95% confidence interval (95% CI) 1.02-3.35]. This trend was not in evidence among the men. CONCLUSIONS: While the study confirms the etiologic role of ionizing radiation, with a higher incidence of thyroid cancer being recorded for the most-exposed female workers, our results do not support the possibility of occupational exposure to ELFMF being a risk factor for the development of thyroid cancer.

Adult↗

PubMed2005

Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis.

Splenic marginal zone lymphoma (SMZL) is a newly recognized lymphoma type whose precise molecular pathogenesis is still essentially unknown. This hampers differential diagnosis with other small B-cell malignancies. With the aim of characterizing this tumor more comprehensively, and of identifying new diagnostic and prognostic markers, we performed cDNA microarray expression profiling and tissue microarray (TMA) immunohistochemical studies in a relatively large series of 44 SMZLs. The results were related to immunoglobulin heavy chain variable region (IgV(H)) mutational status and clinical outcome. SMZLs display a largely homogenous signature, implying the existence of a single molecular entity. Of the genes deregulated in SMZLs, special mention may be made of the genes involved in B-cell receptor (BCR) signaling, tumor necrosis factor (TNF) signaling and nuclear factor-kappaB (NF-kappaB) activation, such as SYK, BTK, BIRC3, TRAF3, and LTB. Other genes observed were SELL and LPXN, which were highly expressed in spleen, and lymphoma oncogenes, such as ARHH and TCL1. In contrast, the genes CAV1, CAV2, and GNG11 located in 7q31, a commonly deleted area, were down-regulated in the entire series. A comparison with the genes comprising the signature of other small B-cell lymphomas identified 3 genes whose expression distinguishes SMZL, namely ILF1, SENATAXIN, and CD40. Shorter survival was associated with CD38 expression, naive IgV(H) genes, and the expression of a set of NF-kappaB pathway genes, including TRAF5, REL, and PKCA.

Biomarkers, Tumor↗

PubMed2005

Cutaneous melanoma in Swedish women: Occupational risks by anatomic site.

BACKGROUND: Few occupational studies have addressed melanoma in women. Accordingly, our aim was to identify occupations with higher risk of cutaneous melanoma, overall and by site, in Swedish female workers. METHODS: All gainfully employed Swedish women were followed-up from 1971 to 1989, using Death/Cancer Registers. Occupational risk ratios adjusted for age, period, town size, and geographic zone were computed for each site. Risk patterns for different sites were then compared. RESULTS: High risks were observed among educators, bank tellers, dental nurses, librarians/archivists/curators, horticultural workers, and hatmakers/milliners. Telephone operators and textile workers had increased risk, mainly in the leg. Other occupation-specific site excesses were also found. Upper-limb risks were correlated with head/neck and thorax, though these two sites were not associated. Legs registered a special pattern, with a moderate correlation with upper limbs or thorax, and no correlation with head/neck. CONCLUSIONS: Some occupations with possible exposure to arsenic/mercury displayed increased risk. The generalized excess risk among hatmakers/milliners warrants further attention. The weak correlation between legs and other sites suggests site specificity in melanoma risk factors.

Adult↗

PubMed2005

[Variation in the prognostic value of p53 protein in relation to tumoral stage in patients with colorectal adenocarcinoma].

OBJECTIVE: To analyze the prognostic value of p53 protein as a marker of recurrence risk in each tumoral stage. PATIENTS AND METHOD: A prospective study of a cohort of 288 patients who underwent surgery for colorectal adenocarcinoma was performed. Stage 1 of the tumor-node-metastasis (TNM) classification was found in 42 patients (14.6%), stage II in 144 (50%) and stage III in 102 (35.4%). Histopathological variables were examined in tumor samples fixed in formol and embedded in paraffin and p53 (DO7 antibody) and proliferative cell nuclear antigen (PC-10 antibody) proteins were determined using immunohistochemistry. The results of p53 were analyzed in each of the categories of clinical and histopathological variables. Recurrence-free survival was calculated using the Kaplan-Meier method. The value of each variable as a predictive marker for tumoral recurrence was analyzed using Cox regression analysis. Hazard ratios and 95% confidence intervals were calculated as indicators of relative risk. The analysis was applied to the whole cohort and was subsequently repeated in each TNM tumoral stage separately. RESULTS: Tumors with p53 protein overexpression more frequently recurred and showed lower recurrence-free survival at 5 years. However, the association between p53 expression and postoperative outcome was statistically significant in stage III tumors only. In this subgroup of patients, recurrence-free survival at 60 months was 60% in p53-negative tumors and was 26% in p53-positive tumors (p=0.010). In the multivariate analysis, p53 was an independent prognostic factor associated with a high risk of recurrence in stage III tumors (hazard ratio=2.76; 95% CI, 1.29-5.9; p=0.009). Overexpression of p53 showed prognostic value as a marker of high risk of recurrence in the form of metastases (hazard ratio=2.23; 95% CI, 1.04-4.75), but not as a prognostic marker of locoregional recurrence. No relationship was found between the state of p53 protein and the effect of postoperative adjuvant therapy. CONCLUSION: The p53 protein does not have the same prognostic value in all tumoral stages. This protein is only predictive of high recurrence risk in the subgroup of patients with stage III tumors.

Adenocarcinoma↗

PubMed2005

Occupation and thyroid cancer risk in Sweden.

OBJECTIVE: The objective of this study was to identify occupations and industries with increased incidence of thyroid cancer in Swedish workers. METHOD: Standardized incidence ratios were computed for each job and industry for the period 1971-1989 through record-linkage with the Swedish National Cancer and Death Registers. Age-, period-, geographically adjusted relative risks were calculated using Poisson models. RESULTS: Increased risks were found for teachers, construction carpenters, policemen, and prison/reformatory officials in men, and medical technicians, shop managers, tailors, and shoecutters among women. Industries with risk excess are manufacture of agricultural machinery, manufacture of computing/accessories, and public administration/police among men; and manufacture of prefabricated wooden buildings, electric installation work, and wholesale of live animals/fertilizers/oilseed/grain among women. CONCLUSIONS: Our results corroborate some previously reported increased risks. Further research is needed to assess the influence of specific chemical agents related with some of the highlighted work environments.

Adult↗

PubMed2004

The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer.

Several non-hypercalcemic analogs of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)) show antitumor activity in a subset of cancer patients. High vitamin D receptor (VDR) expression, which is associated with good prognosis but is lost during tumor progression. We show that the SNAIL transcription factor represses VDR gene expression in human colon cancer cells and blocks the antitumor action of EB1089, a 1,25(OH)(2)D(3) analog, in xenografted mice. In human colon cancers, elevated SNAIL expression correlates with downregulation of VDR.

Animals↗

PubMed2004

The variant E233G of the RAD51D gene could be a low-penetrance allele in high-risk breast cancer families without BRCA1/2 mutations.

Six SNPs have been detected in the DNA repair genes RAD51C and RAD51D, not previously characterized. The novel variant E233G in RAD51D is more highly represented in high-risk, site-specific, familial breast cancer cases that are not associated with the BRCA1/2 genes, with a frequency of 5.74% (n = 174) compared to a control population (n = 567) and another subset of breast cancer patients (n = 765) with a prevalence of around 2% only (comparison to controls, OR = 2.6, 95% CI 1.12-6.03; p < 0.021). We found that the immunohistochemical profile detected in available tumors from these patients differs slightly from those described in non-BRCA1/2 tumors. Finally, the structural prediction of the putative functional consequence of this change indicates that it can diminish protein stability and structure. This suggests a role for E233G as a low-penetrance susceptibility gene in the specific subgroup of high-risk familial breast cancer cases that are not related to BRCA1/2.

Age of Onset↗

PubMed2004

Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer.

The nuclear pore complex protein Nup88 is overexpressed in tumor cells. Immunohistochemical studies have shown that this overexpression is linked to higher aggressiveness of colorectal carcinoma and to enhanced metastatic potential of melanoma cells. However, the antibodies so far developed against Nup88 have the drawback of recognizing a number of other, up to now unspecified antigens besides Nup88. For this reason, we devised the present study on Nup88 expression at the mRNA level. RNA was extracted from fresh tumor tissue corresponding to 122 breast cancer patients. Nup88 mRNA expression was measured by means of differential RT-PCR, standardizing against a constitutive internal control gene (beta-actin). The results were dichotomized into "high" and "low" expression levels, using the median value as cut-off. High Nup88 mRNA expression levels correlated significantly with ductal and tubular histology (p = 0.012), histologic and nuclear grade 3 of tumors (p < 0.001), absence of hormone receptor expression (p < 0.001), expression of the c-erb-B2 oncogene (p < 0.001), expression of mutant p53 protein (p < 0.001), high proliferation (defined by Ki67 labeling index >20%, p < 0.001), DNA aneuploidy (p < 0.001) as well as the most important ominous clinical prognostic factor, axillary node invasion (p < 0.001). We also found an inverse correlation (p < 0.001) with expression of the H-MAM (mammaglobin) gene, a marker of low biologic and clinical aggressiveness of breast cancer. All of these factors, without exception, define a highly aggressive tumor phenotype. These findings appear to be specific to Nup88 and not to nuclear pore proteins in general. Indeed, analysis of Nup107 (which is a limiting component of the nuclear pore complex) under the same conditions in the same tumors did not yield comparable results.

Adenocarcinoma↗

PubMed2004

Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissue microarray-based study.

Cutaneous malignant melanoma remains the leading cause of skin cancer death in industrialized countries. Clinical and histological variables that predict survival, such as Breslow's index, tumor size, ulceration, or vascular invasion have been identified in malignant melanoma. Nevertheless, the potential relevance of biological variables still awaits an in-depth exploration. Using tissue microarrays (TMAs), we retrospectively analyzed 165 malignant melanoma samples from 88 patients corresponding to distinct histological progression phases, radial, vertical, and metastases. A panel of 39 different antibodies for cell cycle, apoptosis, melanoma antigens, transcription factors, DNA mismatch repair, and other proteins was used. Integrating the information, the study has identified expression profiles distinguishing specific melanoma progression stages. Most of the detected alterations were linked to the control of cell cycle G1/S transition; cyclin D1 was expressed in radial cases 48% (12 of 25) with significant lost of expression in vertical cases 14% (9 of 65), P = 0.002; whereas p16(INK4a) (89% in vertical versus 71% in metastatic cases, P = 0.009) and p27(KIP1) (76% in radial versus 45% in vertical cases, P = 0.010) were diminished in advanced stages. The study also defines a combination of biological markers associated with shorter overall survival in patients with vertical growth phase melanoma, that provided a predictor model with four antibodies (Ki67, p16(INK4a), p21(CIP1), and Bcl-6). This predictor model was validated using an independent series of 72 vertical growth phase melanoma patients.

Adult↗

PubMed2004

Building an outcome predictor model for diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) patients are treated using relatively homogeneous protocols, irrespective of their biological and clinical variability. Here we have developed a protein-expression-based outcome predictor for DLBCL. Using tissue microarrays (TMAs), we have analyzed the expression of 52 selected molecules in a series of 152 DLBCLs. The study yielded relevant information concerning key biological aspects of this tumor, such as cell-cycle control and apoptosis. A biological predictor was built with a training group of 103 patients, and was validated with a blind set of 49 patients. The predictive model with 8 markers can identify the probability of failure for a given patient with 78% accuracy. After stratifying patients according to the predicted response under the logistic model, 92.3% patients below the 25 percentile were accurately predicted by this biological score as "failure-free" while 96.2% of those above the 75 percentile were correctly predicted as belonging to the "fatal or refractory disease" group. Combining this biological score and the International Prognostic Index (IPI) improves the capacity for predicting failure and survival. This predictor was then validated in the independent group. The protein-expression-based score complements the information obtained from the use of the IPI, allowing patients to be assigned to different risk categories.

Adolescent↗

PubMed2003

Clinical value of p53, c-erbB-2, CEA and CA125 regarding relapse, metastasis and death in resectable non-small cell lung cancer.

The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), loco-regional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung-cancer recurrence. They can add useful information regarding the complex nature of prognosis.

Adenocarcinoma↗

PubMed2003

Polymorphisms G691S/S904S of RET as genetic modifiers of MEN 2A.

Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germ-line missense mutations in the RET proto-oncogene. Only a minor fraction of human disorders are simple monogenic diseases, and the identification of polymorphisms that increase susceptibility, including variations in pathological phenotypes, to human diseases is one of the key problems in medical genetics. To explore this idea, we analyzed the polymorphisms G691S (exon 11) and S904S (TCC-TCG, exon 15) of RET in 198 individuals corresponding to 35 unrelated Spanish MEN 2A families (104 patients with oncogenic MEN 2A mutation and 94 healthy relatives). We found strong cosegregation between both polymorphisms (100% Fisher's exact test, P < 0.001) using a control population containing 653 healthy individuals (362 females and 291 males). Interestingly, we found that the homozygous for these polymorphisms were, on average, 10 years younger at diagnosis compared with heterozygous and wild-type homozygous (P = 0.037). Taken together, all these findings could indicate that the G691S and S904S variants of RET have a modifier effect on the age at onset of MEN 2A. Moreover, compared with the control population, the homozygote status was significantly more prevalent in a series of 110 sporadic thyroid carcinoma (odds ratio = 2.36), suggesting that these polymorphisms may play a role as a low penetrance risk factor.

Adolescent↗

PubMed2002

Genetic analysis of RET, GFR alpha 1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A.

Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germline missense mutations in the RET proto-oncogene. This locus encodes a receptor tyrosine kinase whose activation requires the formation of a multimeric receptor complex including GDNF as a ligand and GFR alpha 1 as a coreceptor. In order to explore the role of RET, GFR alpha 1 and GDNF genes in the variation of phenotypes observed in MEN2A families, we analysed germline mutations of these genes in 4 unrelated Spanish MEN2A families (23 cases studied). We found 2 novel variants corresponding to a single change in position + 47 (intron 12) of RET and position +22 (intron 7) of GFR alpha 1. Furthermore, we observed strong co-segregation between 2 polymorphisms of RET [G691S (exon 11) and S904S (TCC-TCG, exon 15) (100%, Fisher's exact test, p< 0.001)]. More interestingly, we found that these polymorphisms occurred at a significantly high frequency in patients with age at onset < 20 years old (Kruskal-Wallis's and Fisher's exact test, p = 0.007). These findings suggest that the G691S and S904S variants of RET may somehow play a role on the age of onset of MEN 2A.

Alleles↗

PubMed2002

Occupation, exposure to chemicals and risk of gliomas and meningiomas in Sweden.

BACKGROUND: Occupational exposures may be related to the development of brain cancer. The objective was to estimate occupational-specific risk of gliomas and meningiomas among Swedish men and women gainfully employed in 1970 over the period 1971-1989, and the influence of occupational exposure to chemical substances. METHODS: A dataset linking cancer diagnoses from the Swedish national cancer register to occupational and demographical data obtained in the 1970 census was used to fit log-linear Poisson models, in order to obtain relative risks adjusted by age, period, geographical area and town size. Exposure to 13 chemicals was assessed using a Swedish job-exposure matrix. RESULTS: The main findings of this study among men were the increased risk of glioma with occupational exposure to arsenic, mercury, and petroleum products and of meningioma with lead. Women in occupational sectors with a higher socio-economic status showed an increased incidence of both, gliomas and meningiomas. CONCLUSIONS: Occupational exposure to some chemicals appeared to be related with an increased risk of glioma and meningioma in men. Exposures involved in glioma and meningioma development seemed to be different.

Adult↗