Occupation and breast cancer risk in Polish women: a population-based case-control study

BACKGROUND: The etiology of breast cancer is not well understood and the role of occupational exposures in breast carcinogenesis is still uncertain. METHODS: The population-based case-control study included 2,386 incident breast cancer cases diagnosed in 2000-2003, and 2,502 controls. Lifetime occupational histories and information on other potential breast cancer risk factors were obtained through personal interviews. Conditional logistic regression analyses calculated odds ratios (ORs) associated with various occupations and industries after control for potential confounders. RESULTS: We found statistically significant excesses of breast cancer among engineers (OR=2.0; 95% CI: 1.0-3.8), economists (2.1; 1.1-3.8), sales occupations-retail (1.2; 1.0-1.5), and other sales occupations (1.2; 1.0-1.5). Industries showing significantly elevated risks included special trade contractors (2.2; 1.2-4.3), electronic and electric equipment manufacturers (1.7; 1.1-2.7); and public administration/general government n.e.c. (2.7; 1.3-5.7). Each of these findings was supported by a statistically significant positive trend for duration of employment (P<0.05). A decreased breast cancer risk was observed in janitors and cleaners (0.7; 0.5-0.8). CONCLUSIONS: In this study, we found few associations for breast cancer and occupations or industries. The suggestive findings for the electronic and electric equipment manufacturing industry and for the occupations with potential exposure to magnetic fields deserve further evaluation.     

Lung cancer and occupation in nonsmokers: a multicenter case-control study in Europe

BACKGROUND: Tobacco smoking is the main cause for lung cancer worldwide, making it difficult to examine the carcinogenic role of other risk factors because of possible confounding by smoking. Therefore, the present study aimed to investigate the association between lung cancer and occupation independent of smoking. METHODS: A case-control study of lung cancer was carried out between March 1998 and January 2002 in 16 centers from 7 European countries, including 223 never-smoking cases and 1039 controls. Information on lifestyle and occupation was obtained through detailed questionnaires. Job and industries were classified as entailing exposure to known or suspected carcinogens; in addition, expert assessment provided exposure estimates to specific agents. RESULTS: The odds ratio of lung cancer among women employed for more than 12 years in suspected high-risk occupations was 1.75 (95% confidence interval = 0.63-4.85). A comparable increase in risk was not detected for employment in established high-risk occupations or among men. Increased risk of lung cancer was suggested among individuals exposed to nonferrous metal dust and fumes, crystalline silica, and organic solvents. CONCLUSION: Occupations were found to play a limited role in lung cancer risk among never-smokers. Jobs entailing exposure to suspected lung carcinogens should receive priority in future studies among women. Nonferrous metal dust and fumes and silica may exert a carcinogenic effect independently from smoking.     

Tobacco smoking, NAT2 acetylation genotype and breast cancer risk

The role of active and passive cigarette smoking in breast cancer etiology remains controversial. Using data from a large population-based case-control study in Poland (2386 cases, 2502 controls) conducted during 2000-2003, we examined the associations between active and passive smoking overall and for different age categories. We also evaluated differences in risk by estrogen receptor (ER) and progesterone receptor (PR) status in tumors, and the potential modification of the smoking association by N-acetyl transferase 2 (NAT2) genotype. Women ever exposed to passive smoking at home or at work had a risk of breast cancer similar to those never exposed to active or passive smoking (OR (95%CI) = 1.11 (0.85-1.46), and no trends were observed with increasing hours/day-years of passive smoking exposure. Active smoking was associated with a significant increase in risk only among women younger than 45 years of age (OR (95%CI) = 1.95 (1.38-2.76); 1.15 (0.93-1.40); 0.91 (0.77-1.09) for < 45, 45-55 and > 55 years of age, respectively; p-heterogeneity < 0.001 for < 45 vs. > 55 years) and prevailed for both ER+ and ER- tumors. The smoking association among women < 45 years was stronger for current than former smokers, and a significant trend was observed with duration of smoking (p = 0.04). NAT2 slow vs. rapid/intermediate acetylation genotype was not related to breast cancer risk (0.99 (0.87-1.13)), and did not significantly modify the smoking relationships. In conclusion, our data indicate that passive smoking is not associated with breast cancer risk; however, active smoking might be associated with an increased risk for early onset breast cancers.     

A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23

Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D?' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10(-10) and P = 6.07 × 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.     

Spirometry: a predictor of lung cancer among asbestos workers

Objective: The significance of lung function as an independent risk factor for lung cancer remains unclear. The objective of the study is to answer the question if spirometry can identify patients at risk for lung cancer among people occupationally exposed to asbestos dust in the past.

Methods: In order to identify a group of individuals with the highest risk of lung cancer incidence based on lung function levels of FEV₁% predicted value, we examined 6882 subjects enrolled in the health surveillance program for asbestos related diseases over the years 2000–2014. We found a total of 110 cases confirmed as primary lung cancer.

Results: Using Cox's proportional hazards model after adjustment for age, gender, number of cigarettes, duration of smoking and cumulative asbestos exposure, we estimated that compared with the subjects with FEV₁ ≥90% pred, the HR of lung cancer was 1.40 (95%CI: 0.94–2.08) for the subjects with FEV₁ less than 90% and 1.95 (HR?=?1.86; 95%CI: 1.12–3.08) for those with FEV₁ less than 70%. In addition, probability of the occurrence of lung cancer for FEV₁ <90% of the predicted value was HR?=?2.19 (95%CI: 1.04–4.61) in the subjects whose time since spirometry and cancer diagnosis was three years or less.

Conclusions: The results strongly support the hypothesis that spirometry can identify patients at a risk of lung cancer development. Regular spirometry should be offered to all patients with a history of asbestos exposure, at least once every three years.     

Recombinant alpha-fetoprotein C-terminal fragment: the new recombinant vector for targeted delivery

The specific receptor of alpha-fetoprotein (AFP) is a universal tumor marker, being expressed on the surface of many tumor cells, but not in normal human tissues. AFP enters the cell by receptor-mediated endocytosis; its receptor-binding site is hypothetically localized in the third domain of AFP. A recombinant C-terminal AFP fragment, which contains all the third and a part of the second domains of hAFP, was produced. This AFP fragment was bound specifically to the AFP receptor on the surface of tumor cells and was accumulated by them with the same efficiency as the full-size hAFP. Similar to hAFP, the recombinant C-terminal fragment inhibited the estradiol-induced growth of hormone-dependent MCF-7 cells in vitro. Hence, the recombinant C-terminal AFP fragment can be used as a protein vector for the targeted delivery of cytostatic drugs to tumor cells.     

Vitamin D receptor polymorphisms and renal cancer risk in Central and Eastern Europe

Previous studies investigated the role of vitamin D intake and cancer risk. The kidney is a major organ for vitamin D metabolism, activity, and calcium homeostasis; therefore, it was hypothesized that dietary vitamin D intake and polymorphisms in the vitamin D receptor (VDR) gene may modify renal cell carcinoma (RCC) risk. Three common VDR gene polymorphisms (BsmI, FokI, TaqI) were evaluated among 925 RCC cases and 1192 controls enrolled in a hospital-based case-control study conducted in Central and Eastern Europe. Overall associations with RCC risk were not observed; however, subgroup analyses revealed associations after stratification by median age of diagnosis and family history of cancer. Among subjects over 60 yr, reduced risks were observed among carriers of the f alleles in the FokI single-nucleotide polymorphism (SNP) (odds ratio [OR] = 0.61 for Ff and OR = 0.74 for ff genotypes) compared to subjects with the FF genotype (P trend = 0.04; P interaction = 0.004). Subjects with the BB BsmI genotype and a positive family history of cancer had lower risk compared to subjects with the bb allele (OR = 0.60; 95% CI: 0.33-1.1; P trend = 0.05). Genotype associations with these subgroups were not modified when dietary sources of vitamin D or calcium were considered. Additional studies of genetic variation in the VDR gene are warranted.     

Occupational exposure to dusts and risk of renal cell carcinoma

Background:

Occupational exposures to dusts have generally been examined in relation to cancers of the respiratory system and have rarely been examined in relation to other cancers, such as renal cell carcinoma (RCC). Although previous epidemiological studies, though few, have shown certain dusts, such as asbestos, to increase renal cancer risk, the potential for other occupational dust exposures to cause kidney damage and/or cancer may exist. We investigated whether asbestos, as well as 20 other occupational dust exposures, were associated with RCC risk in a large European, multi-center, hospital-based renal case–control study.

Methods:

General occupational histories and job-specific questionnaires were reviewed by occupational hygienists for subject-specific information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) between RCC risk and exposures were calculated using unconditional logistic regression.

Results:

Among participants ever exposed to dusts, significant associations were observed for glass fibres (OR: 2.1; 95% CI: 1.1–3.9), mineral wool fibres (OR: 2.5; 95% CI: 1.2–5.1), and brick dust (OR: 1.5; 95% CI: 1.0–2.4). Significant trends were also observed with exposure duration and cumulative exposure. No association between RCC risk and asbestos exposure was observed.

Conclusion:

Results suggest that increased RCC risk may be associated with occupational exposure to specific types of dusts. Additional studies are needed to replicate and extend findings.     

Asthma and lung cancer risk: a systematic investigation by the International Lung Cancer Consortium

Asthma has been hypothesized to be associated with lung cancer (LC) risk. We conducted a pooled analysis of 16 studies in the International Lung Cancer Consortium (ILCCO) to quantitatively assess this association and compared the results with 36 previously published studies. In total, information from 585?444 individuals was used. Study-specific measures were combined using random effects models. A meta-regression and subgroup meta-analyses were performed to identify sources of heterogeneity. The overall LC relative risk (RR) associated with asthma was 1.28 [95% confidence intervals (CIs) = 1.16-1.41] but with large heterogeneity (I(2) = 73%, P < 0.001) between studies. Among ILCCO studies, an increased risk was found for squamous cell (RR = 1.69, 95%, CI = 1.26-2.26) and for small-cell carcinoma (RR = 1.71, 95% CI = 0.99-2.95) but was weaker for adenocarcinoma (RR = 1.09, 95% CI = 0.88-1.36). The increased LC risk was strongest in the 2 years after asthma diagnosis (RR = 2.13, 95% CI = 1.09-4.17) but subjects diagnosed with asthma over 10 years prior had no or little increased LC risk (RR = 1.10, 95% CI = 0.94-1.30). Because the increased incidence of LC was chiefly observed in small cell and squamous cell lung carcinomas, primarily within 2 years of asthma diagnosis and because the association was weak among never smokers, we conclude that the association may not reflect a causal effect of asthma on the risk of LC.     

Adulthood lifetime physical activity and breast cancer

BACKGROUND: Epidemiologic studies have shown that breast cancer risk is reduced 30% to 40% in highly physically active compared with inactive women. However, the effects of moderate activities, timing of activities, and intervening effects of other risk factors remain less clear. METHODS: We analyzed data on physical activity patterns in 2176 incident breast cancer cases and 2326 controls in a population-based breast cancer case-control study in Poland conducted in 2000-2003. Using unconditional logistic regression analyses, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) associated with physical activity levels (measured by average metabolic equivalents of energy expenditure hours per week), controlling for potential confounders. RESULTS: Total adult lifetime activity reduced risk of breast cancer, with individuals in the highest quartile having an OR of 0.80 (CI = 0.67-0.96) compared with the lowest quartile. Reduced risks were most consistent for the highest quartiles of moderate-to-vigorous activities: moderate/vigorous recreational activities (OR = 0.74; CI = 0.62-0.89), outdoor activities (0.81; 0.68-0.97), heavy physical work (0.60; 0.42-0.87), and combined high intensity (metabolic equivalent >6.0) activities (0.75; 0.63-0.90). These relations were not modified by body mass index, menopausal status, or family history of breast cancer. Reductions in risk with moderate/vigorous recreational activities were stronger for larger tumors and those with nodal involvement. Women who increased their recreational activity in their 50s had significantly reduced risk, with those in the highest tertile of change being at a 27% lower risk. CONCLUSIONS: Leisure-time moderate-to-vigorous activities reduce breast cancer risk irrespective of underlying host characteristics.