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Objectives: This study investigated the association between lung cancer and waterpipe smoking, which is an emerging global public health concern., Study Design: Multicentre case-control study., Methods: This study included 627 cases and 3477 controls from the Iranian Study of Opium and Cancer (IROPICAN) study, which was conducted between 2017 and 2020. One frequency-matched control for each lung cancer patient was selected by age, gender and residential place; however, this study used controls of four cancer types in the analyses. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence intervals (CIs). Additional analyses were performed among 181 lung cancer cases and 2141 controls who were not cigarette smokers or opium or nass/pipe users., Results: The odds of lung cancer were higher among waterpipe smokers than never-smokers (OR = 1.3, 95% CI: 1.0-1.7). Results showed a higher OR of lung cancer for those who smoked the waterpipe daily (OR = 2.1, 95% CI: 1.4-3.0), smoked more than two heads per day (OR = 2.7, 95% CI: 1.8-4.0), had smoked for >20 years (OR = 1.9, 95% CI: 1.3-2.7), smoked more than 20 head-years (OR = 2.8, 95% CI: 1.9-4.1) and initiated smoking before the age of 30 years (OR = 1.7, 95% CI: 1.1-2.5). The association was only statistically significant for squamous cell carcinomas (OR = 1.8, 95% CI 1.2-2.7). Furthermore, this study observed a higher OR of lung cancer among exclusive waterpipe smokers (OR = 2.3, 95% CI: 1.6, 3.5)., Conclusions: Waterpipe smoking was associated with an increased risk of lung cancer. The association was stronger with higher frequency, duration and intensity of exposure to waterpipe smoking. The association increases in exclusive waterpipe smokers, which is likely due to controlling for residual confounding by cigarette smoking and opium consumption, and higher exposure levels in this subpopulation., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: The rates and routes of Helicobacter pylori transmission, in a high-prevalent country like Iran, with gastric cancer as the leading cause of male cancer mortality, are of great essence. Here, we have studied the H. pylori-associated risk factors and the likelihood of interspousal transmission., Methods: In a cohort of 686 young prewed couples, questionnaires were self-administered and serum samples were collected, for assessment of risk factors and H. pylori serostatus, at baseline and follow-up. Of the 475 H. pylori single- or double-seronegative couples, 201 returned for follow-up. The average follow-up duration was 2.2 (SD 0.6) years, with a total of 560.1 person-years. Logistic regression and Cox regression models were used to estimate the odds ratios (ORs) and hazard ratios (HRs)., Results: The risk of infection was higher in men than women (OR: 1.3, 95% CI: 1.0-1.8) and among metropolitan than rural residents (OR = 1.4, 95% CI: 1.1-1.9). It was also significantly higher among those with three (OR = 1.6, 95% CI: 1.1-2.2), and four or more siblings (OR = 1.4, 95% CI: 1.0-1.9), in reference to those with one or no siblings. Adult H. pylori acquisition occurred in 10.9% (27/247) of the seronegative participants. The risk of the acquisition was significantly associated with age (P value for trend=0,000). It was also significantly lower among participants who had various degrees of education as compared to illiterate subjects (HR = 0.2, 95% CI: 0.1-0.9). Nevertheless, our analysis did not find any evidence for interspousal transmission (HR = 1.0, 95% CI: 0.4-2.2)., Conclusion: Whilst H. pylori acquisition was detected in the young adult Iranian population, our findings did not support interspousal transmission, as a mode of acquisition., Competing Interests: Declaration of competing interest Authors declare no conflicts of interest., (Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Male breast cancer (MBC) is a rare and understudied disease. There is limited evidence on association between environmental and occupational agents and MBC. Some similarities in risk factors may be shared with female breast cancer. We evaluated solvents, metals, exhaust gases and other agents in relation to MBC within the large Nordic Occupational Cancer Study (NOCCA)., Methods: The study included 1469 MBC cases and 7345 controls from Finland, Iceland and Sweden, matched for the date of birth, sex and country. Cases were identified through national cancer registries. Data on occupation and other demographic indicators were collected from census records and population registries. Overall, 24 occupational exposures were assessed. Exposure estimates were assigned by linking job titles to job-exposure matrices (NOCCA-JEM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by using conditional logistic regression models., Results: Significantly decreased overall OR was observed for physical workload (OR = 0.78, 95% CI 0.67-0.91). Protective effect of physical workload was stronger by increasing exposure level with significant dose-response relationship (p-trend<0.01). Non-significantly increased ORs were observed for trichloroethylene, iron, lead, chromium, welding fumes and wood dust, and decreased ORs for asbestos, silica dust and perchloroethylene. However, these results were not consistent across all analyses., Conclusions: The current study showed 20-25% protective effect for physical workload at work, while no strong evidence for other agents was observed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Epidemiological studies of autoimmune hepatitis are scarce and often based on single centre registries., Aims: We conducted a nationwide register study of incidence, prevalence, survival, and causes of death of autoimmune hepatitis patients in Finland., Methods: Autoimmune hepatitis cases 1995-2015 were retrieved from the national database of special reimbursements for drugs costs. Data on causes of death were retrieved from Statistics Finland., Results: After incomplete registration of AIH during the first years, the incidence of autoimmune hepatitis stabilised to 1.1/100,000 person-years (1.6 in women and 0.52 in men) in 2008-2015. The prevalence of autoimmune hepatitis at the end of 2015 was 14.3/100,000, 23.0/100,000 in women and 6.6/100,000 in men. The all-cause standardized mortality ratio (SMR) of autoimmune hepatitis patients was 1.81 (95% confidence interval (CI) 1.47-2.20). The SMR was increased in all age groups and in both sexes. The SMR for hepatocellular carcinoma was 20.6 (95% CI 10.3-36.8), and for digestive diseases in overall 13.5 (95% CI 8.2-20.8), constituting mainly from autoimmune hepatitis and liver cirrhosis., Conclusion: Incidence of autoimmune hepatitis has remained stable, with clear female predominance. Autoimmune hepatitis is associated with a markedly increased risk of death with hepatocellular cancer forming the greatest risk., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives: To determine whether occupational exposure to heavy metals (chromium (VI), iron, nickel, lead) and welding fumes is associated with the risk of kidney cancer and to describe whether other occupational exposures included in the Job Exposure Matrix of the Nordic Occupational Cancer (NOCCA) study are associated with the risk., Materials and Methods: Nested case-control study among individuals registered in population censuses in Finland, Iceland, and Sweden in 1960-1990. A total of 59,778 kidney cancer cases, and 298,890 controls matched on sex, age, and country. Cumulative occupational exposures to metals (chromium (VI), iron, nickel, lead), welding fumes, and 24 other occupational exposure covariates, lagged 0, 10, and 20 years., Results: Overall, there was no or very little association between kidney cancer and exposures studied. The risk was elevated in individuals with high exposure to asbestos (OR 1.19, 95%CI 1.08-1.31). The risk was significantly decreased for individuals characterized with high perceived physical workload (OR 0.86, 95%CI 0.82-0.91), high exposure to ultraviolet radiation (OR 0.85, 95%CI 0.79-0.92), and high exposure to wood dust (OR 0.82, 95%CI 0.71-0.94). The risk of kidney cancer under the age of 59 was elevated in individuals with high exposure to nickel (OR 1.49, 95%CI 1.03-2.17). The risk of kidney cancer in age 59-74 years was elevated for individuals with high exposure to iron (OR 1.41, 95%CI 1.07-1.85), and high exposure to welding fumes (OR 1.43, 95%CI 1.09-1.89)., Conclusions: The only markedly elevated risks of kidney cancer were seen for the highest exposures of nickel and iron/welding fumes in specific age strata., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The aim of this case-control study was to assess the effect of occupational benzene exposure on the risk of colorectal cancer, including its subtypes., Methods: The study included 181,709 colon cancer and 109,227 rectal cancer cases diagnosed between 1961 and 2005 in Finland, Iceland, Norway and Sweden. Cases were identified from the Nordic Occupational Cancer Study (NOCCA) cohort. Five controls per case were selected from the same cohort, matched for country, birth year, and sex. Occupational benzene exposure for each study participant was estimated by linking their job titles to country specific job-exposure matrices. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by using conditional logistic regression models. The results were adjusted for physical strain at work, formaldehyde, ionizing radiation and wood dust., Results: Increased risk was observed for all colorectal cancer (OR = 1.12, 95% CI 1.05-1.18) for the high decile of cumulative benzene exposure, indicating a statistically significant dose-response relationship. This excess risk was mainly seen in ascending colon (OR = 1.27, 95% CI 1.13-1.43), and transversal colon (OR = 1.21, 95% CI 1.01-1.41). The ORs in the highest exposure category were markedly higher in women than in men in all subsites of colon and rectum., Conclusion: This study showed an association between workplace benzene exposure and colorectal cancer. The risk was restricted to ascending and transversal colon, and was the strongest among women., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 were extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals of the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95% confidence interval [CI], 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with primary sclerosing cholangitis (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI, 2.47-7.60), the 1990s: 3.17 (95%CI, 2.70-3.71), to the 2000s: 1.76 (95%CI, 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0-12.9-7.53, and for nonmelanoma skin cancer 80.0-29.7-10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: It has been suggested that long-term activation of the body's stress-response system and subsequent overexposure to stress hormones may be associated with increased morbidity. However, evidence on the impact of major life events on mortality from breast cancer (BC) remains inconclusive. The main aim of this study is to investigate whether major negatively or positively experienced life events before or after diagnosis have an effect on BC-specific mortality in women who have survived with BC for at least 2 years., Methods: We conducted a case fatality study with data on life events from a self-administered survey and data on BC from the Finnish Cancer Registry. Cox models were fitted to estimate BC mortality hazard ratios (MRs) between those who have undergone major life events and those who haven't., Results: None of the pre-diagnostic negative life events had any effect on BC-specific mortality. Regarding post-diagnostic events, the effect was greatest in women with moderate scores of events. As for event-specific scores, increased BC mortality was observed with spouse unemployment, relationship problems, and death of a close friend. By contrast, falling in love and positive developments in hobbies were shown to be associated with lower BC mortality (MRs 0.67, 95%CI: 0.49-0.92 and 0.74, 95%CI: 0.57-0.96, respectively). In an analysis restricted to recently diagnosed cases (2007), also death of a child and of a mother was associated with increased BC mortality., Conclusions: Some major life events regarding close personal relationships may play a role in BC-specific mortality, with certain negative life events increasing BC mortality and positive events decreasing it. The observed favorable associations between positive developments in romantic relationships and hobbies and BC mortality are likely to reflect the importance of social interaction and support., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Lay people and health professionals are increasingly interested in health issues in their region. The high-quality cancer and population registries in the Nordic countries allow fine spatial and temporal visualization of mapped data. This article describes - with real-data examples - a mapping method developed in Finland for such visualization but also utilized for data from numerous other countries and non-cancer outcomes. The Finnish smoothing is based on weighting small-area specific observations with population sizes and distance without losing the interpretability of the values. The approach has essentially improved the readability of spatio-temporal trends of incidence and mortality rates of cancers and has been applied in many studies. With help of the tool, decision makers can understand the key message of existing data and use it more effectively in their efforts to provide better health care services., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The evidence for a relationship between colon cancer incidence and physical activity is not fully convincing, and the association between physical activity and rectal cancer is also unclear. We studied the association between perceived physical workload (PPWL) at work and colorectal cancer, stratified by subsite, in a nested case-control setting in the Nordic Occupational Cancer (NOCCA) data from Finland, Iceland, Norway and Sweden. Five population controls were selected for each cancer patient. PPWL showed a bigger protective effect on colon cancer for males (odds ratio [OR] 0.74 in the highest PPWL decile as compared with the lowest PPWL category, 95% confidence interval [95% CI]: 0.72-0.77) than for females (OR 0.87, 95% CI: 0.81-0.95), with a significant trend for different levels of PPWL for both males and females. In males, the OR of cancer in the descending colon for the highest PPWL decile of males was 0.61 (95% CI: 0.54-0.69). For females the protective effect was most notable in the transversal part of the colon (OR 0.83, 95% CI: 0.67-1.03). The OR for rectal cancer in the highest PPWL decile for males was 0.87 (95% CI: 0.85-0.90) and for females 0.93 (95% CI: 0.83-1.04). Inclusion of further agents in multivariate analyses did not alter the ORs for PPWL. The incidence of colon cancer and, to a lesser extent, rectal cancer is lowest in professions with the highest PPWL. The association is clearer in males than in females. The biggest protective effect appears to be in the descending colon in males., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Short and midterm mortality of patients with osteoarthritis (OA) who have undergone total knee arthroplasty (TKA) is generally lower than that of the general population. Due to an increasing number of young patients who undergo TKA the expected lifetime of these patients is increasing. The purpose of this study was to assess the causes of death and long-term mortality among Finnish TKA patients., Methods: Standardized mortality ratios (SMRs) for total and site specific causes of death were calculated for 9443 TKA patients operated on in 1980 to 1996 for OA and followed until 2012., Results: The mean follow-up time was 14 years (maximum 33 years). During follow-up, 77% of the patients had died. The all-cause SMR was 1.00. It was significantly lower than in the reference population (SMR 0.73) during the first 10 years after operation, but higher during the next 10 years (SMR 1.23), and even more after 20 years (SMR 1.95). The SMR for cardiovascular mortality was 1.03 and accounted for 52% of all deaths. Significant excess mortality was observed in diseases of the digestive tract (SMR 1.29). Deaths due to cardiovascular diseases, Alzheimer's disease and dementia comprised 68% of all deaths that took place 10 years or later after TKA., Conclusions: The mortality of TKA patients with OA is significantly reduced during the first 10 postoperative years but exceeds the mortality of the general population after that. This trend should be taken into account when young patients undergo a TKA., Level of Evidence: Observational study, III., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We aimed to provide the familial risk of classical Hodgkin lymphoma (HL) by relationship, histology, age at diagnosis, and sex. A cohort of 57,475 first-degree relatives of 13,922 HL patients diagnosed between 1955 and 2009 in 5 European countries was observed for HL incidence. The overall lifetime cumulative risk (CR) of HL in first-degree relatives of a patient with HL was 0.6%, which represents a threefold (standardized incidence ratio [SIR], 3.3; 95% confidence interval [CI], 2.8-3.9) increased risk over the general population risk. The risk in siblings (6.0-fold; 95% CI, 4.8- to 7.4-fold) was significantly higher than in parents and/or children (2.1-fold; 95% CI, 1.6- to 2.6-fold). Very high lifetime risk of HL was found for those with multiple affected first-degree relatives (13-fold; 95% CI, 2.8- to 39-fold) and for same-sex twins (57-fold; 95% CI, 21- to 125-fold). We found high familial risks between some concordant histologic subtypes of HL such as lymphocyte-rich (81-fold; 95% CI, 30- to 177-fold) and nodular sclerosis (4.6-fold; 95% CI, 2.9- to 7.0-fold) and also between some discordant subtypes. The familial risk in sisters (9.4-fold; 95% CI, 5.9- to 14-fold) was higher than in brothers (4.5-fold; 95% CI, 2.9- to 6.7-fold) or unlike-sex siblings (5.9-fold; 95% CI, 4.3- to 8.1-fold). The lifetime risk of HL was higher when first-degree relatives were diagnosed at early ages (before age 30 years). This study provides tangible absolute risk estimates for relatives of HL patients, which can be used as a sex-, age-, and family history-based risk calculator for classical HL by oncologists and genetic counselors., (© 2015 by The American Society of Hematology.)

The prevalence of life habits may vary substantially within a country. Incidence maps of strongly related diseases can illustrate the distribution of these life style habits. In this study we explored the spatial variation in Belgium for different cancers related to alcohol and/or tobacco. From the Belgian Cancer Registry, municipality specific World Standardised incidence rates for the years 2004-2011 are used to create detailed smoothed cancer maps by subsite or histology for cancers of oral cavity, pharynx, larynx, oesophagus, liver and lung. Cancer incidence is compared both visually (from incidence maps) and with Poisson regression analysis using mortality from chronic liver disease and chronic obstructive pulmonary disease as a proxy for alcohol and tobacco prevalence, respectively. The incidence rates for oral cavity, pharyngeal and laryngeal cancer were comparable with the alcohol gradient. However, glottic cancer revealed a pattern that was more comparable with lung cancer. These two tumour types resembled more closely to the smoking pattern. Oesophageal cancer showed two patterns: squamous cell carcinoma was highly comparable with the background alcohol consumption, while adenocarcinoma was unrelated to one of our two proxies. Our approach and results are an encouraging example how data from a young cancer registry can be used in studies describing the regional cancer burden. The results can be useful for primary prevention to increase awareness for the public, authorities and health care professionals in specific subpopulations., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to radiation dose and specific chemotherapeutic agents., Patients and Methods: We conducted an international case-control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls., Results: Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5-158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m(2) of procarbazine with nitrogen mustard or ≥3900 mg/m(2) of cyclophosphamide., Conclusion: Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks., (Published by Oxford University Press on behalf of the European Society for Medical Oncology 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Aim: We studied whether incidence of all cancer sites combined was associated with the radiation exposure due to fallout from the Chernobyl accident in Finland. An emphasis was on the first decade after the accident to assess the suggested "promotion effect"., Methods: The segment of Finnish population with a stable residence in the first post-Chernobyl year (2 million people) was studied. The analyses were based on a 250m × 250m grid squares covering all of Finland and all cancer cases except cancers of the breast, prostate and lung. Cancer incidence in four exposure areas (based on first-year dose due to external exposure <0.1 mSv, 0.1-1.3, 0.3-0.5, or ≥ 0.5 mSv) was compared before the Chernobyl accident (1981-1985) and after it (1988-2007) taking into account cancer incidence trends for a longer period prior to the accident (since 1966)., Results: There were no systematic differences in the cancer incidence in relation to radiation exposure in any calendar period, or any subgroup by sex or age at accident., Conclusion: The current large and comprehensive cohort analysis of the relatively low levels of the Chernobyl fallout in Finland did not observe a cancer promotion effect., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use., Design: Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records., Results: The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking)., Conclusions: Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.

Background: Statins (HMG-CoA-reductase inhibitors) are suggested to act as a predisposing factor for autoimmune diseases, have immunomodulatory effects, and possibly prevent some cancer types - the sum of these effects is unknown in cancers of viral aetiology, such as Merkel cell carcinoma (MCC). Aim of our study was to find out whether statin users in Finland have an increased incidence of MCC., Patients and Methods: A cohort of 224715 male and 230220 female statin users during 1994-2007 was identified from the Prescription Register of the National Social Insurance Institution. This cohort was followed up through the Finnish Cancer Registry for MCC up to 2009., Results: There were altogether 50 cases of MCCs, while the expected number of cases, calculated on the basis of the MCC incidence in comparable Finnish population, was 39.9 (SIR 1.25, 95% CI 0.93-1.65). The standardized incidence ratio (SIR) for MCC in ages <60 years was 3.16 (95% CI 0.65-9.23), in ages 60-74 years 1.94 (95% CI 1.23-2.90) and in ages ≥75 years 0.89 (95% CI 0.57-1.31). The relative risk of MCC decreased significantly, 0.79 fold (95% CI 0.67-0.92), at each 5 year step when moving towards older age groups. There was no significant variation in SIR related to years since starting the statin use, or between the genders., Conclusions: MCC is the first neuroendocrine cancer linked to statin use. The association is statistically significant and biologically plausible through immunomodulatory effects of statins. The excess of MCCs was observed in atypically young patients, a similar phenomenon as noted earlier in patients with immunocompromising states., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Stress has been suggested to reduce survival after cancer, but the results of previous studies have been contradictory. We investigated the hypothesis in a national cohort of adults in Finland. Of those who completed the Stressful Life Events scale and the Stress of Daily Activities scale, 1470 and 1882, respectively, later had cancer and were included in the analysis, covering 23 years of follow-up between 1982 and 2004. In Cox regression analysis, the multivariate hazard ratio (HR) was 0.99 (95% confidence interval [CI], 0.96-1.01) for total number of life events and the HR for the life change score was 0.99 (95% CI, 0.95-1.03). Further, the HR was 0.92 (95% CI, 0.69-1.22) for severe daily stress. Overall, the results of the current study do not support the hypothesis that stress reduces cancer survival., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. MCCs and some other skin cancers, such as basal cell carcinomas, frequently harbour Merkel cell polyomavirus DNA. The purpose of the study was to investigate the frequency of second cancers following the diagnosis of MCC. We studied the incidence of second primary cancers after the diagnosis of MCC from the files of the Finnish Cancer Registry in 1979-2006. Among the 172 MCC patients identified a total of 34 second primary cancers were detected in 30 individuals after the diagnosis of MCC. Female MCC patients were diagnosed with 25 subsequent cancers (SIR, 2.35; 95% CI, 1.52-3.47; p<0.001) and male patients with 9 cancers (SIR, 2.32, 95% CI, 1.06-4.40; p<0.05). The MCC patients had an increased risk for a subsequent cancer (any site) compared to age-, gender- and calendar period-matched general population (standardized incidence ratio [SIR] 2.34; 95% confidence interval [CI], 1.62-3.27). The risks for basal cell carcinoma of the skin (O=11), SIR, 3.48; 95% CI, 1.74-6.22 and chronic lymphocytic leukemia (O=2), SIR, 17.9; 95% CI, 2.16-64.6 were significantly elevated. The SIRs for an overall second primary cancer risk did not change markedly with time since the diagnosis of MCC. We conclude that patients diagnosed with MCC have an increased risk for a second cancer. This risk may in part result from shared etiological factors between MCC and other tumour types, such as immunosuppression or possibly Merkel cell polyomavirus infection.

Purpose: Lycopene is thought to decrease the risk of cancers, although previous epidemiologic studies have produced inconsistent results. The aim of the present study was to evaluate the protective effect of lycopene against the risk of cancer., Methods: The study population consisted of 997 middle-aged Finnish men in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort. During the mean follow-up time of 12.6 years, a total of 141 cancer cases appeared, of which 55 were prostate cancers. The association between the serum concentrations of lycopene and the risk of cancer was studied using the Cox proportional hazard models., Results: An inverse association was observed between serum lycopene and overall cancer incidence. The adjusted risk ratio (RR) in the highest tertile of serum lycopene was 0.55 (95% confidence interval [CI], 0.34-0.89; p=0.015) compared with the lowest serum lycopene group. No association was observed between the lycopene concentrations and a prostate cancer risk. RR for other cancers was 0.43 (95% CI, 0.23-0.79; p=0.007)., Conclusions: These findings suggest that in middle-aged men, the higher circulating concentrations of lycopene may contribute to the lower risk of cancer, with the exception of prostate cancer.

Purpose: The aim of this study is to quantify excess absolute risk (EAR) and excess relative risk (ERR) of secondary leukemia among a large population-based group of testicular cancer survivors., Methods: We identified 42,722 1-year survivors of testicular cancer within 14 population-based cancer registries in Europe and North America (1943-2002). Poisson regression analysis was used to model EAR (per 100,000 person-years [PY]) and ERR of secondary leukemia. Cumulative risks were calculated using a competing risk model., Results: Secondary leukemia developed in 89 patients (EAR = 10.8 per 100,000 PY, 95% confidence interval [CI] = 7.6-14.6; ERR = 1.6, 95%CI = 1.0-2.2). Statistically significantly elevated risks were observed for acute myeloid leukemia (AML) (EAR = 7.2, 95%CI = 4.7-10.2) and acute lymphoblastic leukemia (EAR = 1.3, 95%CI = 0.4-2.8). In multivariate analyses, AML risk was higher among patients whose initial management included chemotherapy compared to those receiving radiotherapy alone (p = 0.1). Excess cumulative leukemia risk was approximately 0.23% by 30 years after testicular cancer diagnosis., Conclusions: Although ERR of leukemia following testicular cancer is large, EAR and cumulative risk, which are better gauges of the population burden, are small.

Water from bedrock frequently contains higher concentrations of natural radionuclides than water from other sources. Bladder and kidneys receive a radiation dose when radioactive isotopes are excreted into urine. The subjects for this case-cohort study were selected from all drilled wells users in Finland. The study comprised 61 bladder cancer and 51 kidney cancer cases diagnosed between 1981 and 1995, as well as a random sample of 274 reference persons, stratified by age and sex. The median activity concentrations of radon in drilled wells used by bladder and kidney cancer cases and the reference cohort were 170, 140, and 130 Bq/L, respectively. The radium concentration was 0.01 Bq/L for all groups and the uranium concentrations were 0.08, 0.07, and 0.06 Bq/L, respectively. The bladder cancer risks associated with radon, radium, and uranium activity concentrations in drinking water were 1.02 (0.68-1.54) per log(100 Bq of radon/L), 0.73 (0.21-2.50) per log(0.1 Bq of radium/L), and 0.77 (0.32-1.89) per log(1 Bq of uranium/L). The corresponding figures for kidney cancer were 0.81 (0.47-1.37), 0.12 (0.01-1.10), and 0.92 (0.36-2.35), respectively. In conclusion, even though ingested radionuclides from drilled wells are a source of radiation exposure, they are not associated with a substantially increased risk of bladder or kidney cancers in concentrations occurring in drilled wells.

Background and Aim: To assess the long-term risks of malignant diseases and mortality in patients with coeliac disease and dermatitis herpetiformis in a centre, where the prevalence of these diseases is high. The risks have probably been overestimated, as patients with subtle forms have earlier remained undetected., Patients: The study comprised 17,245 person-years of follow-up in 1147 patients., Methods: The observed numbers of malignancies and causes of deaths were assessed, and compared to those expected, and standardised incidence ratio and standardised mortality ratio given., Results: The occurrence of all malignant conditions was equal to that in the population both in coeliac disease and dermatitis herpetiformis: standardised incidence ratios of 1.2 (95% confidence intervals 0.9-1.5) and 1.0 (0.6-1.5), respectively. Five patients with coeliac disease and seven with dermatitis herpetiformis had developed non-Hodgkin lymphoma; standardised incidence ratios of 3.2 (1.0-7.5) and 6.0 (2.4-12.4), respectively. Four patients with coeliac disease and one with dermatitis herpetiformis had enteropathy-associated T-cell lymphoma, associated with inadequate dietary compliance. Mortality was increased (standardised mortality ratio 1.26; 1.00-1.55) in coeliac disease, but decreased in dermatitis herpetiformis (standardised mortality ratio 0.52; 0.36-0.72)., Conclusion: The overall prognosis in our patients was good. Non-Hodgkin lymphoma emerged in patients with undiagnosed or poorly treated coeliac disease. The mortality rate in dermatitis herpetiformis was even lower than in the population. Our data support the early diagnosis and dietary treatment of these conditions.

The importance of genetic and other risk factors in the development of breast cancer after radiotherapy (RT) for Hodgkin lymphoma (HL) has not been determined. We analyzed data from a breast cancer case-control study (105 patients, 266 control subjects) conducted among 3 817 survivors of HL diagnosed at age 30 years or younger in 6 population-based cancer registries. Odds ratios (ORs) and excess relative risks (ERRs) were calculated using conditional regression. Women who received RT exposure (> or = 5 Gy radiation dose to the breast) had a 2.7-fold increased breast cancer risk (95% confidence interval (CI) 1.4-5.2), compared with those given less than 5 Gy. RT exposure (> or = 5 Gy) was associated with an OR of 0.8 (95% CI, 0.2-3.4) among women with a first- or second-degree family history of breast or ovarian cancer, and 5.8 (95% CI, 2.1-16.3) among all other women (interaction P = .03). History of a live birth appeared to increase the breast cancer risk associated with RT among women not treated with ovarian-damaging therapies. Breast cancer risk following RT varied little according to other factors. The additional increased relative risk of breast cancer after RT for HL is unlikely to be larger among women with a family history of breast or ovarian cancer than among other women.

Objective: Infection with oncogenic human papillomaviruses (HPVs) is the most important cause of cervical cancer worldwide. After infection there is a long latency period of at least 10 to 15 years during which cervical cancer develops in a small proportion of originally infected women. Up to 50% of these women have at diagnosis antibodies to the HPV oncoproteins E6 and E7, which are rarely found among healthy women. Our purpose was to evaluate whether antibodies to HPV16 and HPV18 E6 and E7 proteins are useful for early diagnosis of cervical cancer by measuring the antibody response in women in whom cervical cancer later developed., Study Design: A joint serum bank of 550,000 Swedish, Norwegian, and Finnish women was followed up for 0.5 to 20 years, after which 178 invasive cervical carcinoma (ICC) cases, 150 of whom had squamous cell carcinoma (SCC), and 527 controls were identified. Antibodies to HPV16 and HPV18 E6 and E7 proteins were determined by tag enzyme-linked immunoassays., Results: HPV16/18 E6 and E7 antibodies were detected infrequently (7.0%) in women in whom SCC later developed and yielded a moderately increased estimate of associated relative risk (odds ratio 2.7, 95% CI 1.1-6.4). Sensitivity of the combined antibody tests for the detection of occult SCC varied between 6% and 14% but was not related to time lag between serum sampling and cancer diagnosis., Conclusion: HPV16/18 E6 and E7 antibody responses are not sensitive markers of occult cervical cancer.

Objective: Hysterectomy with bilateral oophorectomy has been suggested to increase the risk of thyroid cancer. We studied the relationship between hysterectomy and thyroid cancer in a population-based setting in Finland., Study Design: Women undergoing hysterectomy between 1986 and 1995 (n = 17,900) were identified from the National Hospital Discharge Registry. The cohort was followed up through the Finnish Cancer Registry until 1997., Results: There were 118 cases of thyroid cancer diagnosed, 103 papillary and 15 follicular or medullar type. The incidence for thyroid cancer was significantly elevated (standardized incidence ratio [SIR] 1.38, 95% CI 1.15-1.64). The increase in the incidence of thyroid cancer was not dependent on the extent of operation but on the length of follow-up. Thyroid cancer incidence was increased 0.5 to 1.4 years after hysterectomy (SIR 2.00, 95% CI 1.31-2.93), but decreased thereafter (SIR 1.30, 95% CI 0.99-1.67). Hysterectomy with and without oophorectomy was associated with a similar increase in the incidence of thyroid cancer., Conclusion: Women who have undergone hysterectomy have an increased risk of thyroid cancer during the first 2 years after the operation. Thyroid cancer and bleeding disorders may share a common background.

Little has been known about the molecular background of familial multiple cutaneous leiomyomatosis (MCL). We report here a clinical, histopathological, and molecular study of a multiple cutaneous leiomyomatosis kindred with seven affected members. This detailed study revealed strong features of a recently described cancer predisposition syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC). The family was compatible with linkage to the HLRCC locus in 1q. Also, all seven cutaneous leiomyomas derived from the proband and analyzed for loss of heterozygosity displayed loss of the wild-type allele, confirming the association with a susceptibility gene in chromosome 1q. One individual had had renal cell cancer at the age of 35 years. This tumor displayed a rare papillary histopathology, which appears to be characteristic for HLRCC. The derived linkage, loss of heterozygosity, and clinical data suggest that MCL and HLRCC are a single disease with a variable phenotype. The possibility that members of leiomyomatosis families are predisposed to renal cell cancer should be taken into account.

Background: Dermatomyositis and polymyositis are associated with cancer, but previous nationwide studies have not had sufficient cases to test the association between myositis and specific cancer types. Our aim was to investigate the risk of specific cancer types in individuals with dermatomyositis and polymyositis., Methods: We did a pooled analysis of published national data from Sweden, Denmark, and Finland. All patients with dermatomyositis and polymyositis (> or =15 years old) were identified by discharge diagnosis from the Swedish National Board of Health (1964-83), Danish Hospital Discharge Registry (1977-89), and Finnish National Board of Health (1969-85). Personal details were matched to national cancer registries, to identify all cases of cancer up to 1987 in Sweden, 1995 in Denmark, and 1997 in Finland, and to national death registries for the same periods. We calculated standardised incidence ratios (SIR) for individual cancer sites for dermatomyositis and polymyositis separately, using national cancer rates by country, sex, age, and date., Findings: We identified 618 cases of dermatomyositis, of whom 198 had cancer. 115 of the 198 developed cancer after diagnosis of dermatomyositis. This disease was strongly associated with malignant disease (SIR 3.0, 95% CI 2.5-3.6), particularly ovarian (10.5, 6.1-18.1), lung (5.9, 3.7-9.2), pancreatic (3.8, 1.6-9.0), stomach (3.5, 1.7-7.3), and colorectal (2.5, 1.4-4.4) cancers, and non-Hodgkin lymphoma (3.6, 1.2-11.1). 137 of the 914 cases of polymyositis had cancer, which developed after diagnosis of polymyositis in 95. Polymyositis was associated with a raised risk of non-Hodgkin lymphoma (3.7, 1.7-8.2), and lung (2.8, 1.8-4.4) and bladder cancers (2.4, 1.3-4.7). In both dermatomyositis and polymyositis, risk of malignant disease was highest at time of myositis diagnosis., Interpretation: Our results provide evidence that dermatomyositis is strongly associated with a wide range of cancers. The overall risk of malignant disease is also modestly increased among patients with polymyositis, with an excess for some cancers.

As putative etiologic factors of primary cutaneous T cell lymphomas may have a general cancerogenic effect, we wanted to assess the risk of secondary malignancies in 319 patients diagnosed with histopathologically verified cutaneous T cell lymphomas and reported to the Finnish Cancer Registry during the years 1953-95. Standardized incidence ratios were defined as the ratio of observed to expected numbers of cases. To obtain the expected numbers of cancer, age-, sex-, and period-specific Finnish incidence rates were applied to the appropriate person-years under observation. Ninety-five percent confidence intervals were calculated assuming a Poisson distribution. For the whole period, we detected 36 secondary cancers whereas 26 were expected (standardized incidence ratios 1.4, 95% confidence intervals 1.0-1.9). The overall risk of lung cancer was significantly increased (standardized incidence ratio was 2.7, 95% confidence intervals were 1.4-4.8); and in particular small-cell lung cancer showed high standardized incidence ratios (standardized incidence ratio was 8.5, 95% confidence intervals were 2.8-20). Also, the risk of lymphomas was elevated (standardized incidence ratios for Hodgkin and non-Hodgkin lymphomas combined were 7.0, 95% confidence intervals were 1.9-18). The incidence of other cancers was similar to the national ratios. An increased risk of secondary cancers and in particular small-cell cancer of the lung and lymphomas among patients with primary cutaneous T cell lymphoma is demonstrated. In clinical practice, lung cancer and lymphomas must be kept in mind when following up patients with cutaneous T cell lymphomas.

This study was designed to estimate the relative cancer risk of patients with moderate to severe psoriasis, with reference to different treatments. A cohort of 5687 hospitalized patients with psoriasis obtained from the Finnish Hospital Discharge Register in 1973-84 was linked with the records of the Finnish Cancer Registry. Standardized incidence ratios for cancer were calculated by dividing the observed number of cases by the expected cases, which were based on the national sex-specific and age-specific cancer incidence rates. By the end of 1995, 533 cancer cases were observed in the cohort. The overall cancer incidence was increased (standardized incidence ratio 1.3, 95% confidence interval 1.2-1.4). The estimated relative risks were highest for Hodgkin's disease (standardized incidence ratio 3.3, 95% confidence interval 1.4-6.4), squamous cell skin carcinoma (standardized incidence ratio 3.2, 95% confidence interval 2.3-4.4), non-Hodgkin's lymphoma (standardized incidence ratio 2.2, 95% confidence interval 1.4-3.4), and laryngeal cancer (standardized incidence ratio 2.9, 95% confidence interval 1.5-5.0). The role of prior oral antipsoriatic medications or phototherapy on the development of these cancers was assessed in a nested case-control study, for which 67 cases and 199 sex and age matched controls were selected from the psoriasis cohort. The relative risks were estimated using conditional logistic regression analysis. Oral 8-methoxy-psoralen plus ultraviolet-A radiation therapy and the use of retinoids were associated with an increased risk of squamous cell skin carcinoma (relative risk adjusted for the other treatment variables 6.5, 95% confidence interval 1.4-31, and 7.4, 95% confidence interval 1.4-40, respectively), whereas none of the treatments could be linked with the occurrence of non-Hodgkin's lymphoma.

Study Objectives: To explore whether the progression of asbestosis correlates with the risk of lung cancer among patients with asbestosis., Design: A group of 85 asbestosis patients (78 men and 7 women) were radiographically followed up between 1979 and 1987. Two or three posteroanterior radiographs taken from each patient in 1978 to 1979, 1983 to 1984, and 1986 to 1987 were classified according to the International Labour Office 1980 classification and were used to divide the patients into progressors and nonprogressors. Follow-up for cancer was done automatically through the files of the Finnish Cancer Registry from the time of determination of the progression status to December 31, 1994. Predictors of lung cancer risk were studied with a logistic regression model, and the standardized incidence ratio (SIR) was calculated for lung cancer., Results: Of the 24 male patients with progressive small opacity profusion, 11 (46%) developed lung cancer, as opposed to 5 (9%) of the 54 male patients without progression. The SIR for lung cancer was 37 (95% confidence interval, 18 to 66) for the progressors and 4.3 (1.4 to 9.9) for the nonprogressors. In both groups, all the lung cancer cases occurred among smokers or ex-smokers. None of the seven female patients showed progressive small opacity profusion. One of them developed lung cancer. In the logistic regression model including all 85 asbestosis patients, radiographic progression of small opacity profusion (p=0.0009) and current smoking (0.0021) were significant predictors of lung cancer morbidity., Conclusions: Asbestosis patients with radiographic progression of small opacity profusion over a few years are at a higher risk of lung cancer than those with a less aggressive course of the disease. The progression of pulmonary fibrosis may be an independent risk factor that, in addition to smoking history and the intensity of asbestos exposure, could be used to estimate lung cancer risk.

The aim of the study was to create a rapid method for estimating cancer risk in areas defined by exact map coordinates and to test it using as an example incidence of leukemia near an oil refinery. The method can be used to investigate possible local excesses of cancer of suspected environmental origin in Finland. Map coordinates with an accuracy of 10 m for the place of residence of each Finn were obtained from national registers. Based on this data set, numbers of inhabitants and expected number of cancer cases by sex and age in squares of 500 x 500 m were calculated for all of Finland. Observed number of cancer cases in each square were obtained based on record linkage of the map coordinates with the Finnish Cancer Registry. The ratio of observed and expected number of cancer cases was modeled using Poisson regression. The example analysis included all 23 leukemia and 531 any cancer cases registered in an area around an oil refinery in 1983-1986. There was no significant association between distance from the oil refinery and risk of leukemia or any cancer. The method proved fast and efficient in comparing areal differences in cancer incidence in Finland. In cases of environmental concern, geographical analyses of existing registers is a rapid method to perform first analyses when evaluating the need for further studies.

It is not clear whether screening for breast cancer works as public health policy and whether early indicators of effect predict an ultimate reduction in mortality. The malignant potentials of 248 breast cancers detected by the screening service in Finland were compared with those of 490 control cancers diagnosed before the screening service was established. Aggressiveness was assessed by DNA flow cytometry and clinical status by cancer size and node involvement. After the first screening round, the results of DNA flow cytometry were the same in cancers diagnosed by screening and in controls; these findings are consistent with the hypothesis that the biological aggressiveness of breast cancer remains constant as the cancer progresses. The proportion of patients with node-negative and small T1 cancers after the first screening was higher among the screened population than among controls, indicating earliness of diagnosis among those screened. Cancers diagnosed in the first round had a low malignant potential, as indicated by the DNA flow-cytometry and by clinical stage. Lower aggressiveness of cancers found by screening than of control cancers would indicate overdiagnosis or length-biased sampling, but not earliness of diagnosis. Screening with mammography is practised as a public-health policy in Finland. The results predict that the mortality reduction found in randomised trials can be repeated with a screening service.

The incidence of hereditary nonpolyposis colorectal cancer (HNPCC) is not precisely known. Common estimates are 4 to 6% of all colorectal cancers (CRCs), but lower figures have been published. In an attempt to obtain an independent new estimate of this proportion and to identify more HNPCC families, we designed a new method. Based on the fact that age at diagnosis is considerably lower in hereditary than in sporadic CRC, a cohort of 227 CRC patients aged 44 years or younger diagnosed during the years 1985-1989 and reported to the Finnish Cancer Registry was chosen as probands. Pedigrees of the probands were constructed by combining information from the Finnish Population Register Center and Finnish Cancer Registry using only automatically processed data. Sixteen pedigrees were extended further by the help of parish registers. Six of these turned out to be new possible HNPCC families but none met the stringent criteria of the cancer syndrome. Our results can be interpreted to suggest that the proportion of HNPCC of all CRCs is between 0.5 and 0.9%, depending on the diagnostic criteria used. Modifications of our method should be useful in other research projects dealing with diseases in which a subset is due to genetically or environmentally determined susceptibility.

The relationship between dietary fat and subsequent risk of breast cancer was studied in 3988 initially cancer-free Finnish women aged 20-69 y. During a follow-up period of 20 y, 54 breast-cancer cases were diagnosed. Risk of breast cancer was significantly inversely related to energy intake and nonsignificantly inversely related to absolute fat intake. A positive association between energy-adjusted total fat intake and occurrence of breast cancer was also observed. The relative risk in the highest tertile as compared with the lowest tertile was 1.7 (95% confidence limits 0.6-4.8). The corresponding relative risks were 1.4 (0.5-3.7) for saturated fatty acids, 2.7 (1.0-7.4) for monounsaturated fatty acids, 1.2 (0.6-2.8) for polyunsaturated fatty acids, and 2.2 (1.0-5.0) for cholesterol intake. Adjustment for different potential confounding factors did not alter the results. The present data suggest that breast cancer is associated inversely with energy intake and weakly positively with energy-adjusted fat intake.