Applying recommended definition of aggressive prostate cancer: a validation study using high-quality data from the Cancer Registry of Norway.

BACKGROUND: The Prostate Cancer Cohort Consortium (PC3) Working Group proposed a definition for aggressive prostate cancer (PC) for aetiologic epidemiologic research. We aimed to validate this definition as well as a second approach utilising only information on stage at diagnosis. METHODS: First primary PCs diagnosed 2004 - 2009 in the population-based Janus Serum Bank (JSB) cohort were identified by linkage to the population-based Cancer Registry of Norway (CRN) (n = 3568). The CRN and Norwegian Prostate Cancer Registry provided clinicopathological data for these cases. Approach 1 classified PC as aggressive if it was clinically T4, or N1, or M1, or had a Gleason score ≥8 at diagnosis (as proposed). Approach 2 classified PC as aggressive if CRN stage at diagnosis was 'regional spread' or 'distant metastases'. Both approaches were validated by calculating the sensitivity and positive predictive value (PPV) against PC-death within 10 years of diagnosis. RESULTS: Overall, 555 died from PC within 10 years. Approach 1 classified 24.7% of cases as aggressive and 13.6% were unclassified due to missing information. Approach 2 classified 19.6% as aggressive and 29% were unclassified. Sensitivity was highest for Approach 1 (0.76, 95% CI: 0.72 - 0.80 vs 0.69, 95% CI: 0.64 - 0.73), while PPVs were similar for both approaches (0.43, 95% CI: 0.40 - 0.46 and 0.40, 95% CI: 0.36 - 0.44). We observed similarly high sensitivity and higher PPVs than those reported by the PC3 Working Group. CONCLUSIONS: The proposed definition of aggressive PC was applicable and valid in the JSB cohort. Stage at diagnosis can be useful if data on cTNM or Gleason score is unavailable.

Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

Mortality from non-malignant diseases in a cohort of female pulp and paper workers in Norway.

OBJECTIVES: The objective of the present study was to investigate the risk of death from non-malignant diseases in female pulp and paper workers in Norway. METHODS: A total of 3143 women first employed between 1920-93 were included in the study cohort. Information about each cohort member was obtained from personnel record files in the mills in order to identify employment periods and job categories. Data on cause and date of death were added by linkage to the Cause of Death Register using unique personal identification numbers. The follow up period was 1951-2000. Standardised mortality ratios (SMRs) with 95% confidence intervals (95% CIs) were calculated using the national female mortality rates as reference. Poisson regression analysis was used to examine internal relations between the duration of employment in paper departments and the risk of death from selected causes. Relative risks (RRs) and 95% CIs were calculated. RESULTS: The study showed a significantly increased risk for total non-malignant mortality (SMR = 1.14, 95% CI 1.05 to 1.24), mainly due to increased mortality from ischaemic heart disease (SMR = 1.22, 95% CI 1.03 to 1.43) and cerebrovascular diseases (SMR = 1.16, 95% CI 0.94 to 1.42). Analysis by department showed the highest risk of death in paper department workers with short term employment. Internal analyses showed a 5% and 9% increase in risk of dying from ischaemic heart disease and respiratory diseases, respectively, among paper department workers exposed to paper dust. The risk decreased with increasing duration of employment. CONCLUSION: The increased risk of ischaemic heart diseases and respiratory diseases seen among employees of paper departments may be related to exposure to paper dust.

Cancer incidence among male pulp and paper workers in Norway.

OBJECTIVES: The study investigated cancer incidence among 23,718 male pulp and paper workers employed continuously for at least 1 year between 1920 and 1993 in Norway. METHODS: The name, date of birth, personal identification number, dates of hire and termination for all employment periods, specific department, and job categories were registered for each worker. Six subcohorts were established (sulfite mill, sulfate mill, paper mill, maintenance department, administrative staff and other departments). Data on the cohort were linked with data in the Norwegian Cancer Register. The follow-up period for cancer incidence, date of death, or emigration was from 1953 through 1993. RESULTS: An excess incidence of lung cancer was found among both short- and long-term employees [standardized incidence ratio (SIR) 1.5, 95% confidence interval (95% CI) 1.13-2.03 and SIR 1.2, 95% CI 1.09-1.34, respectively], especially for workers with the longest latency (SIR 1.3, 95% CI 1.08-1.44) and for sulfite mill workers (SIR 1.5, 95% CI 1.09-1.99). The risk for pleural mesothelioma was also increased (SIR 2.4, 95% CI 1.45-3.75), especially among maintenance workers. The results also showed an increased risk for malignant melanoma (SIR 1.3, 95% CI 1.04-1.60), an unexpected finding. CONCLUSIONS: Almost all the increased risk for lung cancer can be explained by a combination of smoking habits and asbestos use. although an effect of other work-related exposures (sulfur and chloride compounds, wood dust) cannot be excluded. Most of the cases of pleural mesothelioma occurred in departments where asbestos was used. There is no clear explanation for the excess of malignant melanoma, and the finding may be a chance occurrence.

Perineal use of talc and risk of ovarian cancer.

Ovarian cancer is one of the most common gynaecological neoplasms, especially in industrialised countries. The aetiology of the disease is not well understood, except that inherited mutations in the breast cancer genes BRCA-1 and BRCA-2 account for up to 10% of all cases, and child-bearing, oral contraceptive use and breast-feeding reduce the risk. Some environmental exposures, notably talc and asbestos, have been suspected as ovarian carcinogens.

Asbestos fibers in ovarian tissue from Norwegian pulp and paper workers.

An elevated risk of ovarian cancer has been observed in Norwegian pulp and paper workers who were possibly occupationally exposed to asbestos. The present study was initiated to investigate if the increased risk could be associated with asbestos fibers in ovarian tissue from workers in this industry. Normal ovarian tissue specimens from three groups of women were included in the study. The case group included specimens from 46 women diagnosed with ovarian cancer in the period 1953-2000, and who had been working in one or more pulp and paper mills between 1920 and 1993. Normal ovarian tissue specimens from two control groups without occupational history from pulp and paper work were selected from the Cancer Registry database. Tissue blocks were digested and prepared for transmission electron microscopy. Number of fibers per gram wet weight was calculated. Asbestos fibers were found in normal ovarian tissue from two subjects in the case group, while no fibers were found in the control groups. The two asbestos positive cases had been working as paper sorter/packer and chlorine plant worker, respectively. Both were possibly secondary exposed to asbestos from family members working as insulators. We conclude that the findings in this study did not allow drawing any firm conclusion about an association between occupational exposure to asbestos and ovarian cancer in Norwegian pulp and paper workers. Our study confirms that asbestos fibers may reach the ovaries and demonstrates that the applied method is appropriate for identification of the fibers.

Cancer incidence among women in the Norwegian pulp and paper industry.

BACKGROUND: The aim of the present study was to investigate cancer risk among women working in the Norwegian pulp and paper industry. The cohort included a total of 4,247 workers employed for at least one year between 1920 and 1993 (108,095 person-years), 85% of them as paper or administration workers. METHODS: The follow-up period for cancer was from 1953-1993. No data of exposure measurements were available. The analyses were based on comparisons of standard incidence ratios. The expected numbers of cancer cases were calculated using the five-year age-specific incidence rates for the entire female population. RESULTS: During the follow-up period, 380 new cases of cancer were observed vs. 322 expected (SIR = 1.2, 95% CI = 1.07-1.30). An excess risk of ovarian cancer was found (SIR = 1.5, 95% CI = 1.07-2.09). The SIR was highest among those younger than 55 years, and mostly among those working in paper departments. Short-term workers showed increased risk of lung and bladder cancer. CONCLUSIONS: Based on results from the present study, the increased risk of ovarian cancer is difficult to interpret, since existing knowledge of its etiology is limited. However, these women might have been exposed to various work-related agents such as talc, microbes, and different types of paper dust.

Lung and bladder cancer in a Norwegian municipality with iron and steel producing industry: population based case-control studies.

OBJECTIVES: To investigate the influence of occupation on the rising incidence of lung and bladder cancer among men in a Norwegian municipality where an iron and steel plant constituted the key industry between 1955 and 1989. METHODS: Based on the lung cancer cases reported to the Cancer Registry of Norway from 1980 to 1992 a population based case-control study was performed, including 86 cases and 196 controls. Information on occupations and smoking habits was collected through interviews and from the personnel files from the industrial plants. A case-control study on bladder cancer with 52 cases and 156 controls was carried out to cast light on the role of polycyclic aromatic hydrocarbons (PAHs). RESULTS: An odds ratio (OR) for lung cancer of 2.9 (95% confidence interval (95% CI) 1.2 to 6.7) was associated with exposure to PAHs. Based on data from personnel files, increased risk of lung cancer (OR 2.8 95% CI 1.1 to 7.0) was associated with work experience in the pig iron department at the ironworks. A non-significant OR of 1.8 was associated with exposure to asbestos. Bladder cancer was not associated with exposure to PAHs at the iron, steel, and coke plant, or with experience from any of the production departments at the plant. CONCLUSIONS: One fifth of the lung cancer cases were attributed to exposure to PAHs or asbestos. More than 80% of the cases of lung cancer were attributed to tobacco smoking. The cancer risk in the pig iron department may be due to a combination of exposures to PAH, asbestos, or dust of mixed composition.

[Pulmonary function in Norwegian farmers keeping domestic animals]. / Lungefunksjon blant norske husdyrbønder.

In a group of farmers keeping domestic animals, all pulmonary function tests, except for PEF, showed lower values than in a Norwegian reference population. Spirometric values for FVC, FEV1, and PEF were higher among pig farmers than among other farmers. Poultry farmers had lower values of PEF compared to other farmers. One third of all farmers had values of FEF25-75% that were depressed more than 20%, possibly indicating that the smaller, more peripheral airways more frequently are affected than the central airways. No single causal factor for the reduced lung function was found, but farmers that worked in newer cow-stables had a lower lung function than other farmers, especially if the houses were built in the interval 1975-84.

BRCA1 mutations in ovarian cancer and borderline tumours in Norway: a nested case-control study.

The aims of the present study were to find the frequency of the most common BRCA1 mutations in women with ovarian tumours identified from a population-based cancer registry and in the general population, to estimate the relative risk of ovarian tumours among the mutation carriers, and to explore the value of using CA125 as a prediagnostic test. The study was designed as a nested case-control study within a cohort mainly consisting of participants in population-based health examinations. The data files of The Cancer Registry of Norway and the Janus serum bank were linked to identify cases with ovarian cancer and borderline tumours. Hereditary BRCA1 mutations were determined using archived serum samples and capillary electrophoresis. Altogether 478 ovarian cancer patients and 190 patients with borderline tumours were identified, and 1421 and 568 matching controls were selected. Odds ratios (OR) of developing ovarian cancer and borderline tumours in the presence of BRCA1 mutations and CA125 level were derived from conditional logistic regression models. Among the 478 ovarian cancer patients, 19 BRCA1 mutations were identified (1675delA, 1135insA, 816delGT and 3347delAG), none among the patients with borderline tumours. Only two of the 1989 controls were BRCA1 mutation carriers (0.10%). The risk of ovarian cancer among the mutation carriers was strongly elevated (OR=29, 95% CI=6.6-120). CA125 was a marker for ovarian cancer, but the sensitivity was low. This study showed that BRCA1 mutation carriers have a very high risk of ovarian cancer. However, since the prevalence of BRCA1 mutations in the Norwegian population was low, the proportion of ovarian cancers due to BRCA1 mutations seemed to be low, about 4%. The sensitivity of using CA125 only as a screening test for ovarian cancer was low.