Mortality from lung cancer in workers exposed to sulfur dioxide in the pulp and paper industry

Our objective in this study was to evaluate the mortality of workers exposed to sulfur dioxide in the pulp and paper industry. The cohort included 57,613 workers employed for at least 1 year in the pulp and paper industry in 12 countries. We assessed exposure to SO(2) at the level of mill and department, using industrial hygiene measurement data and information from company questionnaires; 40,704 workers were classified as exposed to SO(2). We conducted a standardized mortality ratio (SMR) analysis based on age-specific and calendar period-specific national mortality rates. We also conducted a Poisson regression analysis to determine the dose-response relations between SO(2) exposure and cancer mortality risks and to explore the effect of potential confounding factors. The SMR analysis showed a moderate deficit of all causes of death [SMR = 0.89; 95% confidence interval (CI), 0.87-0.96] among exposed workers. Lung cancer mortality was marginally increased among exposed workers (SMR = 1.08; 95% CI, 0.98-1.18). After adjustment for occupational coexposures, the lung cancer risk was increased compared with unexposed workers (rate ratio = 1.49; 95% CI, 1.14-1.96). There was a suggestion of a positive relationship between weighted cumulative SO(2) exposure and lung cancer mortality (p-value of test for linear trend = 0.009 among all exposed workers; p = 0.3 among workers with high exposure). Neither duration of exposure nor time since first exposure was associated with lung cancer mortality. Mortality from non-Hodgkin lymphoma and from leukemia was increased among workers with high SO(2) exposure; a dose-response relationship with cumulative SO(2) exposure was suggested for non-Hodgkin lymphoma. For the other causes of death, there was no evidence of increased mortality associated with exposure to SO(2). Although residual confounding may have occurred, our results suggest that occupational exposure to SO(2) in the pulp and paper industry may be associated with an increased risk of lung cancer.     

Rare alleles at different VNTR loci among lung-cancer patients with microsatellite instability in tumours

Work in our laboratory has shown a significantly higher frequency of microsatellite mutations in tumours from lung-cancer patients with rare alleles at the Hras1 VNTR locus compared with those with common alleles. In 137 lung-cancer patients, the association between microsatellite instability and rare alleles at the Hras1 VNTR locus was confirmed with 17 microsatellite markers. We found a significant association between LOH in lung tumours of marker D3s966 with microsatellite instability. In samples with LOH at marker D3s966 (3p21.3) 22% of loci tested showed instability, whereas 8% showed instability without LOH at D3s966. To investigate whether rare alleles at the Hras1 locus are linked to rare alleles at other loci, a second minisatellite (D17S4) was genotyped. In a population of 406, 4 individuals with D17S4 rare alleles were detected of whom 3 also had rare alleles at the Hras1 VNTR locus. The probability of this association to occur by chance is low. Thus, rare alleles at the Hras1 locus may be associated with rare alleles at other loci, and could be an indication of germline instability. The findings indicate that microsatellite instability in lung tumours is not strictly associated with features in the Hras1 proto-oncogene, but may be the result of the same mechanism(s) that generate(s) new alleles at the Hras1 and D17S4 loci. Int. J. Cancer, 70:412–415, 1997. © 1997 Wiley-Liss, Inc.     

A pooled analysis of second primary pancreatic cancer

Studies of pancreatic cancer in the setting of second primary malignant neoplasms can provide etiologic clues. An international multicenter study was carried out using data from 13 cancer registries with a registration period up to year 2000. Cancer patients were followed up from the initial cancer diagnosis, and the occurrence of second primary malignant neoplasms was compared with expected values derived from local rates, adjusting for age, sex, and period of diagnosis. Results from individual registries were pooled by use of a fixed-effects model. People were at higher risk of developing pancreatic cancer within 10 years of a diagnosis of cancers of the pharynx, stomach, gallbladder, larynx, lung, cervix, corpus uteri, bladder, and eye and 10 years or later following a diagnosis of cancers of the stomach, colon, gallbladder, breast, cervix, placenta, corpus uteri, ovary, testis, bladder, kidney, and eye, as well as Hodgkin's and non-Hodgkin's lymphomas. Pancreatic cancer was connected with smoking-related cancers, confirming the etiologic role of tobacco. The associations with uterine and ovarian cancers suggest that reproductive factors might be implicated in pancreatic carcinogenesis. The elevated pancreatic cancer risk in young patients observed among several types of cancer implies a role of genetic factors. Radiotherapy is also suggested as a risk factor.     

Smokeless tobacco use and risk of cancer of the pancreas and other organs

Little information is available on the role of tobacco, alcohol and diet in the survival of upper aero digestive cancers. Our study analysed the survival of 931 laryngeal and hypopharyngeal cancer patients, enrolled in a population based case-control study conducted at 5 centres in southeast Europe during 1979-1982. Age at the time of diagnosis and site of origin of tumour were observed to be predictors of the survival. Cigarette smoking, and to a limited extent alcohol drinking, before the diagnosis of tumour seem to influence the overall survival whereas high intakes of vegetables and vitamin C were observed to favourably affect the prognosis. For mortality from upper aerodigestive cancer protective effects of high intakes of vegetables, fibres and vitamin C were observed. Our results support the hypothesis that there is a role for dietary intervention to improve survival of laryngeal and hypopharyngeal cancer patients.     

Is birth history the key to highly educated women's higher breast cancer mortality? A follow‐up study of 500,000 women aged 35–54

A positive relationship has been found between high levels of education and breast cancer mortality. The aim of our study is to determine if the educational gradient in breast cancer mortality persists after adjustment for reproductive history. Register data including the total adult population in Norway were used. A total of 512,353 Norwegian women 35-54 years of age at the Norwegian Census in 1990 were followed with respect to breast cancer deaths until December 31, 2001. The analysis included 2,052 breast cancer deaths in 5.6 million person years. Educational differences in breast cancer mortality were analysed using Cox regression. The age adjusted relative risk of dying from breast cancer for women with >12 years of education compared to women with <10 years was 1.25 (95% confidence limits [CI] = 1.10-1.41). Adjustment for age at first birth with nulliparous as reference category reduced this difference to 1.08 (95% CI = 0.95-1.23). For parous women, age at first birth explained all the educational difference in breast cancer mortality. Among nulliparous women there was a larger positive educational gradient in breast cancer mortality than among parous women (relative risk [RR] = 1.57, 95% CI = 1.15-2.13), indicating that there were differences in other confounders than birth history among the childless.     

A phase II study of ifosfamide, carboplatin and cisplatin in advanced and recurrent squamous cell carcinoma of the uterine cervix

BACKGROUND:: Discouraging response durations and long-time survivals haveso far been the result of cisplatin-containing combination chemotherapyagainst advanced or recurrent squamous cell carcinoma of theuterine cervix. In order to increase the platinum-based effectupon this tumor without an increase in the specific toxicityof cisplatin, we combined it with carboplatin, added ifosfamide,which has been shown to possess a comparable degree of single-agentactivity. PATIENTS AND METHODS:: Thirty-six patients with advanced or recurrent squamous cellcarcinoma of the uterine cervix not curable by radiation orsurgery were treated with a combination of ifosfamide 1.5 gr/m²i.v. days 1–3, carboplatin 200 mg/m² i.v. day 1, and cisplatin50 mg/ml² Thirty-one patients were evaluable for response and34 patients for toxicity. RESULTS:: Twenty-three patients responded (64%), 11 (31%) of them completely,and 12 (33%) partially. Median response duration was 23 weeks(range 8–107 weeks), reaching 27 weeks and 21 weeks patientswith and without disease in previously irradiated areas, respectively.Median survival is 40 weeks (range 1–114 weeks). Toxicityconsisted mainly of moderate to severe myelosuppression, resultingin 2 toxic deaths. CONCLUSION:: The response rate, also for earlier irradiated areas, comparesfavorably with other known cisplatin-containing regimens. Thecombination deserves investigation in a randomized setting. Uterine cervical cancer, advanced, recurrent, chemotherapy     

Incidence of cancer among male waiters and cooks: two Norwegian cohorts

Previous occupational survey studies have identified waiter and cook as possible high risk occupations for cancer. However, few cohort studies have been performed among persons in the restaurant business, and we therefore have analyzed cancer incidence in two cohorts of Norwegian waiters and cooks. The cohorts consisted of skilled male workers, 1,463 waiters and 2,582 cooks, who received their craft certificate between 1958 and 1983. The cohorts were followed from 1959 through 1991. The standardized incidence ratio (SIR) for all causes of cancer was 1.4 (95 percent confidence interval [CI]=1.2–1.7] for waiters, and 1.1 (CI=0.9–1.4) for cooks. Cancers of the tongue, mouth, pharynx, larynx, esophagus, and liver were grouped together as alcohol-associated cancers. SIR for these cancers combined was 5.1 (CI=3.4–-7.4) for waiters and 4.2 (CI=2.2–7.2) for cooks. For lung cancer, SIR was 2.0 (CI=1.3–2.9) for waiters and 0.7 (CI=0.2–1.7) for cooks. For alcohol-associated cancers, the analysis carried out according to number of years since first employment showed a larger number of cases than expected for both occupations in all time-periods. The excess of lung cancer cases among waiters appeared after 30 years or more of employment. The study shows that waiters and cooks are at high risk of cancers associated with alcohol consumption, and that waiters, in addition, show high rates for lung cancer. The hypothesis of an occupational lung-cancer risk in cooks was not supported by this study.Dr Kjerheim and Mr Andersen are with The Cancer Registry of Norway. Address crrespondence to Dr Kjerheim, The Cancer Registry of Norway, Institute for Epidemiological Cancer Research, Montebello, 0310 Oslo, Norway. This project was supported by grants from the Confederation of Norwegian Business and Industry.     

Estrogen receptor expression and gene promoter methylation in non-small cell lung cancer - a short report

Purpose

In the past, anomalous estrogen receptor (ER) regulation has been associated with various lung pathologies, but so far its involvement in lung cancer initiation and/or progression has remained unclear. Here, we aimed at assessing in vivo and in vitro ER expression and its possible epigenetic regulation in non-small cell lung cancer (NSCLC) samples and their corresponding normal tissues and cells.

Methods

ERα and ERβ gene expression levels were assessed using real time quantitative PCR (RT-qPCR), whereas ERα and ERβ gene promoter methylation levels were assessed using DNA bisulfite conversion followed by pyrosequencing. We included NSCLC (n = 87) and adjacent histologically normal lung tissue samples from lung cancer patients (n = 184), primary normal bronchial epithelial-derived cell cultures (n = 11), immortalized bronchial epithelial-derived cell lines (n = 3) and NSCLC derived cell lines (n = 9).

Results

Using RT-qPCR we found significantly lower ERα and ERβ expression levels in the NSCLC tissue samples compared to their normal adjacent tissue samples. These lower ER expression levels were confirmed in vitro using primary normal bronchial epithelial-derived cell cultures, immortalized bronchial epithelial-derived cell lines and NSCLC-derived cell lines. By using this latter panel of cells, we found that ER gene promoter hypermethylation was associated with decreased ER expression. In addition we found that in tumor and normal lung tissues, smoking was associated with decreased ER expression and that normal lung tissues with a low ERβ expression level exhibited increased smoking-related DNA adducts.

Conclusions

Taken together, our results indicate that decreased ER expression mediated by DNA methylation may play a role in NSCLC development.

     

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non-melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.     

Cancer of the gastrointestinal tract and exposure to asbestos in drinking water among lighthouse keepers (Norway)

Objective Previous studies of predominantly ecological design have indicated a possible elevation of gastrointestinal cancer risk in population groups exposed to drinking water contaminated with asbestos from natural sources or asbestos–cement containing water pipes. In the present study the possible effect of ingested asbestos fibers on gastrointestinal cancer risk was investigated in an occupational group where a proportion of the employees was exposed to asbestos in their drinking water.Method A cohort of 726 lighthouse keepers first employed between 1917 and 1967 were followed up for cancer incidence from 1960 to 2002. The standardized incidence ratio (SIR) was calculated as the number of new cancer cases divided by the expected number based on five-year age and sex specific incidence rates in the general rural population of Norway. A 95% confidence interval (CI) was calculated for all SIR values assuming a Poisson distribution of the cancer cases.Results Risk of stomach cancer was elevated in the whole cohort (SIR: 1.6, CI: 1.0–2.3), in the subgroup with definite asbestos exposure (SIR: 2.5, CI: 0.9–5.5), and when the group was followed for 20 years and more after first possible exposure (SIR: 1.7, CI: 1.1–2.7). Less consistent results were found for colon cancer; SIR was 1.5 (CI: 0.9–2.2) overall, 0.8 (CI: 0.1–2.9) among the exposed, and 1.6 (CI: 1.0–2.5) twenty years and more after first possible exposure.Conclusion The results support the hypothesis of an association between ingested asbestos and gastrointestinal cancer risk in general and stomach cancer risk specifically.