Neonila Szeszenia-Dąbrowska

Differences in Risk Factors for Breast Cancer Molecular Subtypes in a Population-Based Study

Analysis of gene expression data suggests that breast cancers are divisible into molecular subtypes which have distinct clinical features. This study evaluates whether pathologic features and etiologic associations differ among molecular subtypes. We evaluated 804 women with invasive breast cancers and 2,502 controls participating in a Polish Breast Cancer Study. Immunohistochemical stains for estrogen receptor α, progesterone receptor, human epidermal growth factor receptors (HER2 and HER1), and cytokeratin 5 were used to classify cases into five molecular subtypes: luminal A, luminal B, HER2-expresing, basal-like, and unclassified. Relative risks were estimated using adjusted odds ratios and 95% confidence intervals. We observed that compared with the predominant luminal A tumors (69%), other subtypes were associated with unfavorable clinical features at diagnosis, especially HER2-expressing (8%) and basal-like (12%) tumors. Increasing body mass index significantly reduced the risk of luminal A tumors among premenopausal women (odds ratios, 0.71; 95% confidence intervals, 0.57-0.88 per five-unit increase), whereas it did not reduce risk for basal-like tumors (1.18; 0.86-1.64; Pheterogeneity = 0.003). On the other hand, reduced risk associated with increasing age at menarche was stronger for basal-like (0.78; 0.68-0.89 per 2-year increase) than luminal A tumors (0.90; 0.95-1.08; Pheterogeneity = 0.0009). Although family history increased risk for all subtypes (except for unclassified tumors), the magnitude of the relative risk was highest for basal-like tumors. Results from this study have shown that breast cancer risk factors may vary by molecular subtypes identified in expression studies, suggesting etiologic, in addition to clinical, heterogeneity of breast cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(3):439–43)

Established breast cancer risk factors by clinically important tumour characteristics.

Breast cancer is a morphologically and clinically heterogeneous disease; however, it is less clear how risk factors relate to tumour features. We evaluated risk factors by tumour characteristics (histopathologic type, grade, size, and nodal status) in a population-based case–control of 2386 breast cancers and 2502 controls in Poland. Use of a novel extension of the polytomous logistic regression permitted simultaneous modelling of multiple tumour characteristics. Late age at first full-term birth was associated with increased risk of large (>2 cm) tumours (odds ratios (95% confidence intervals) 1.19 (1.07–1.33) for a 5-year increase in age), but not smaller tumours (P for heterogeneity adjusting for other tumour features (Phet)=0.007). On the other hand, multiparity was associated with reduced risk for small tumours (0.76 (0.68–0.86) per additional birth; Phet=0.004). Consideration of all tumour characteristics simultaneously revealed that current or recent use of combined hormone replacement therapy was associated with risk of small (2.29 (1.66–3.15)) and grade 1 (3.36 (2.22–5.08)) tumours (Phet=0.05 for size and 0.0008 for grade 1 vs 3), rather than specific histopathologic types (Phet=0.63 for ductal vs lobular). Finally, elevated body mass index was associated with larger tumour size among both pre- and postmenopausal women (Phet=0.05 and 0.0001, respectively). None of these relationships were explained by hormone receptor status of the tumours. In conclusion, these data support distinctive risk factor relationships by tumour characteristics of prognostic relevance. These findings might be useful in developing targeted prevention efforts.

Estimating age-specific breast cancer risks: A descriptive tool to identify age interactions

ObjectiveClarifying age-specific female breast cancer risks and interactions may provide important etiologic clues.MethodUsing a population-based case–control study in Poland (2000–2003) of 2,386 incident breast cancer cases and 2,502 control subjects aged 25–74 years, we estimated age-specific breast cancer incidence rates according to risk factors.ResultsBreast cancer risks were elevated among women with positive family history (FH), younger age at menarche, older age at first full-term birth, nulliparity, exogenous hormonal usage, and reduced physical activity (PA). Notwithstanding overall risks, we observed statistically significant quantitative (non-crossover) and qualitative (crossover) age interactions for all risk factors except for FH and PA. For example, nulliparity compared to parity reduced breast cancer risk among women ages 25–39 years then rates crossed or reversed, after which nulliparity increased relative risks among women ages 40–74 years.ConclusionThough quantitative age interactions could be expected, qualitative interactions were somewhat counterintuitive. If confirmed in other populations, qualitative interactions for a continuous covariate such as age will be difficult to reconcile in a sequential (multistep or monolithic) ‘stochastic’ breast cancer model. Alternatively, the reversal of relative risks among younger and older women suggests subgroup heterogeneity with different etiologic mechanisms for early-onset and late-onset breast cancer types.

Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10−8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2–TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci—9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301–HLA-DQA1*0103–HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10−9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10−6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

Asbestos in Poland: occupational health problems.

The presentation addresses current problems of health risk and health effects associated with exposure to asbestos, including data on historical exposure and on currently valid occupational exposure limits. The quantity and types of the raw material used for the production of various asbestos products have also been discussed in relation to the particular types of asbestos-induced occupational diseases. The authors describe the medical care system for former asbestos workers and those currently exposed during removal of asbestos-containing products. The national system for medical certification of occupational asbestos-related diseases and the compensation procedure have been outlined as well. According to the parliamentary Act of 1997, importing, manufacture and sale of asbestos and asbestos-containing materials are prohibited in Poland. Thus, the assessment of asbestos exposure and the monitoring of health conditions of workers at asbestos-processing plants have become irrelevant. However, the delayed health effects attributable to past exposure continue to be the matter of concern for public health. Likewise, the environmental pollution from asbestos waste landfills in the vicinity of asbestos-processing plants (where high levels of asbestos fibre in ambient air have been recorded) will continue to be a serious public health problem. Presently, two programmes aimed at minimising the adverse effects of asbestos on population health are underway. One of them is the governmental programme for “Elimination of asbestos and asbestos-containing products used in Poland, 2002–2032”. The programme was updated in 2009 to cover the workers contracted to perform demolition works and provide protective covers to asbestos waste landfills. This will be the exposed group who need prophylactic health care. The other is a programme of prophylactic examinations for former asbestos workers and is referred to as the AMIANTUS programme. Both programmes have been briefly described.

Intrauterine environment and breast cancer risk in a population-based case-control study in Poland†

High estrogen exposure in utero may increase breast cancer risk later in life. However, studies of the associations between perinatal factors presumed to affect the fetal hormonal environment and breast cancer risk are inconsistent. We used data from a population‐based case‐control study of 2,386 incident breast cancers and 2,502 controls in Poland to evaluate risks associated with various perinatal characteristics. After adjusting for confounders, we found a significant trend (p = 0.01) of breast cancer risk with birth weight (OR = 1.54, 95% CI 1.08–2.19 for birth weights >4,000 g vs. <2,500 g). Subjects with a high birth order (≥6) were at reduced risk (OR = 0.81, 0.61–1.06) when compared with first born subjects. Birth weight was somewhat a stronger risk predictor among subjects whose cancers were diagnosed at 50 years of age or older (OR = 1.84, 1.19–2.85) than among those with cancers diagnosed at younger ages (OR = 1.14, 0.61–2.12). Subjects whose mothers smoked during their pregnancies were at slightly higher risk than those who never smoked (OR = 1.21, 0.99–1.47), but the risk was similar to mothers who only smoked at other times (OR = 1.22, 0.81–1.84). Breast cancer risk was not related to paternal smoking, maternal age, gestational age or twin status. Our results add support to the growing evidence that some perinatal exposures may relate to breast cancer risk. Additional studies are needed to confirm associations and clarify the biologic mechanisms underlying these associations. Published 2006 Wiley‐Liss, Inc.

Environmental asbestos pollution — Situation in Poland

ObjectivesEnvironmental exposure of the general population to asbestos in Poland is mainly due to degradation of very popular asbestos-cement products and the resultant release of the elementary asbestos fibres into the ambient air. Assessments of environmental pollution by asbestos were based on the volume of the raw material used, amount of manufactured asbestos products, and measuring the concentration of fibres in the air.Material and MethodsUnder the governmental program intended to remove asbestos, measurements of the concentration of asbestos fibres were performed in 2004–2010 in all provinces of Poland. Considering that potential sources of asbestos dust emissions were present in residential areas, 1634 sampling sites were designated. From 2 to 4 air samples were collected at each sampling site. A total of 5962 samples were collected during seven years. A single dose of air collected by 25 mm 0.8 μm pore Sartorius filter was 1,300 litres. The fibres were counted using optical microscopy with phase contrast (PCM) on a polarizing microscope (PLM) at a total magnification of 600×.; method was adapted to determine the concentration of asbestos fibres in non-occupational environment.ResultsMean concentration of asbestos fibres was 492 f/m3 (95% CI: 467–518). In 82% of the sampling sites, the mean concentrations did not exceed 800 f/m3. As much as 25.8% of the samples were found to be below the detection limit of the method. Estimated mean concentrations of fibres in different provinces ranged from 146 (95% CI: 106–203) to 709 f/m3 (95% CI: 591–851). In the areas affected by former asbestos-processing plants, mean concentration was 732 f/m3 (95% CI: 527–1016) and was significantly higher than levels recorded in other areas of Poland.ConclusionAsbestos consumption per capita and the recorded moderate levels of asbestos fibres concentration in atmospheric air point to a relatively low level of environmental asbestos pollution in Poland.

Predictors of lung cancer among former asbestos-exposed workers.

OBJECTIVES Despite extensive literature concerning the risk of lung cancer incidence among asbestos workers there is still lack of data specifying the association between the level of exposure and the frequency of cancer occurrence. The aim of the analysis was to assess the influence of smoking and selected factors related to occupational exposure on the risk of the incidence of lung cancer among the workers who were exposed to asbestos dust in the past. MATERIAL AND METHODS The assessment was performed based on the case-control studies carried out within a cohort including 7,374 former workers of asbestos processing plants, examined over the years 2000-2013. Analysis of the material was based on the calculation of the odds ratio (OR) using conditional logistic regression modeling, adjusted for cigarette smoking, cumulative exposure, branch and time since last exposure. RESULTS During the survey period there were 165 cases of lung cancer. Among the individuals who smoked, the relative risk of lung cancer incidence was twice as high in the persons smoking more than 20 pack-years (OR=2.23; 95% CI: 1.45-3.46) than it was in the case of the non-smokers. Analysis revealed that the risk of lung cancer in the group with the highest exposure was two times higher in comparison with the low cumulative asbestos exposure (OR=1.99; 95% CI: 1.22-3.25). The risk continued to increase until 30 years after cessation of asbestos exposure and started to decline many years after the last exposure. Influence of the mentioned above characteristics is particularly visible for tumors located in the lower parts of the lungs. CONCLUSION Our findings confirm the strong evidence that the lung cancer risk is associated with asbestos exposure and it increases along with the increasing exposure. A strategy of smoking cessation among the individuals exposed to asbestos dust would potentially have health promoting effects.

Medical monitoring of asbestos-exposed workers: experience from Poland.

Abstract In Poland, the use of asbestos was banned in 1997 and asbestos plants have been closed since then. Despite their closure, cases of asbestos-related occupational diseases among former asbestos workers are still being recorded in the Central Register of Occupational Diseases. Between 2001 and 2014, there were 2726 asbestos-related illnesses, classified and reported as diseases associated with occupational exposure to asbestos. In 2000, Poland introduced a programme called Amiantus, targeted at former asbestos-processing plant workers. The programme provided periodic medical examinations to workers and free access to medications for treatment of asbestos-related illnesses. Introduction of the programme provided additional data to generate a reliable estimation of the number of asbestos-related occupational diseases, including cancer. The average latency period for asbestosis, lung cancer and mesothelioma is about 40 years so there may still be some health impact to former workers necessitating follow-up. We present the Polish experience of implementing a medical examination programme for asbestos-exposed workers and provide a list of activities to consider when planning for such a programme.

Occupational diseases in Poland — An overview of current trends

IntroductionThe number of occupational diseases (OD) recorded in Poland in the 1990’s rapidly increased, and the number of recognized cases has steadily decreased until now. Hence, it was decided to demonstrate the trends of selected pathologies which in Poland are “underestimated” in comparison to other countries. The presented data may constitute a basis for further research into the dependence of OD on socio-economic factors.Materials and MethodsOccupational Disease Reporting Forms, completed and sent obligatorily by the state health inspectors to the Central Register of Occupational Diseases were used as source documents for analysis. This work analyzes changes in the incidence of chronic poisonings, asbestosis, voice organ diseases, cancers, viral hepatitis, asthma and the musculoskeletal disorders over the years 1998–2011.ResultsIn 1998, the total number of registered diseases reached the maximum — 12,017 cases, which fell in the subsequent years to 2,562 cases in 2011. During that period, the incidence rate decreased by 6 cases per year per 100,000 employees. A considerable decrease, exceeding 90% of cases, was observed in voice organ disorders, hearing loss, chronic poisonings and viral hepatitis. The abovementioned changes, as well as improved detection of asbestos-related diseases through implementing a medical examination program of former asbestos processing plant workers, are advantages of the current situation in the epidemiology of OD. However, the disadvantages include underestimation, in comparison to other countries, of asthma, cancer and pathologies of the musculoskeletal system.ConclusionThe reported data indicates the need to assess the occupational fraction of the underestimated pathologies present in the work environment in Poland, as well as the need for studies aimed at clarifying the effect of systemic factors on identifying their occupational background.