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Cancer survival varies widely between countries. The CONCORD study provides survival estimates for 1·9 million adults (aged 15–99 years) diagnosed with a first, primary, invasive cancer of the breast (women), colon, rectum, or prostate during 1990–94 and followed up to 1999, by use of individual tumour records from 101 population-based cancer registries in 31 countries on five continents. This is, to our knowledge, the first worldwide analysis of cancer survival, with standard quality-control procedures and identical analytic methods for all datasets. To compensate for wide international differences in general population (background) mortality by age, sex, country, region, calendar period, and (in the USA) ethnic origin, we estimated relative survival, the ratio of survival noted in the patients with cancer, and the survival that would have been expected had they been subject only to the background mortality rates. 2800 life tables were constructed. Survival estimates were also adjusted for differences in the age structure of populations of patients with cancer. Global variation in cancer survival was very wide. 5-year relative survival for breast, colorectal, and prostate cancer was generally higher in North America, Australia, Japan, and northern, western, and southern Europe, and lower in Algeria, Brazil, and eastern Europe. CONCORD has provided the first opportunity to estimate cancer survival in 11 states in USA covered by the National Program of Cancer Registries (NPCR), and the study covers 42% of the US population, four-fold more than previously available. Cancer survival in black men and women was systematically and substantially lower than in white men and women in all 16 states and six metropolitan areas included. Relative survival for all ethnicities combined was 2–4% lower in states covered by NPCR than in areas covered by the Surveillance Epidemiology and End Results (SEER) Program. Age-standardised relative survival by use of the appropriate race-specific and state-specific life tables was up to 2% lower for breast cancer and up to 5% lower for prostate cancer than with the census-derived national life tables used by the SEER Program. These differences in population coverage and analytical method have both contributed to the survival deficit noted between Europe and the USA, from which only SEER data have been available until now. Until now, direct comparisons of cancer survival between high-income and low-income countries have not generally been available. The information provided here might therefore be a useful stimulus for change. The findings should eventually facilitate joint assessment of international trends in incidence, survival, and mortality as indicators of cancer control. Centers for Disease Control and Prevention (Atlanta, GA, USA), Department of Health (London, UK), Cancer Research UK (London, UK).

This study investigated whether feeding with a highly hydrolyzed milk formula would decrease the incidence of diabetes-associated autoantibodies in genetically susceptible children. The intervention appeared to have a long-lasting effect on markers of beta-cell autoimmunity. Type 1 diabetes is defined by the loss of insulin-producing beta cells in the pancreatic islets in genetically susceptible persons. Overt diabetes is preceded by an asymptomatic period of highly variable duration 1 during which diabetes-associated autoantibodies appear in the peripheral circulation as markers of emerging beta-cell autoimmunity. Five disease-related autoantibodies predict the clinical manifestation of type 1 diabetes: islet-cell antibodies; insulin autoantibodies; and autoantibodies to glutamic acid decarboxylase (GAD), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2), and zinc transporter 8 (ZnT8). 2 , 3 Positivity for two or more antibodies signals a risk of 50 to 100% for the development of type . . .

Objective To examine non-cancer morbidity in the Estonian Chernobyl cleanup workers cohort compared with the population sample with special attention to radiation-related diseases and mental health disorders. Design Register-based cohort study. Setting Estonia. Participants An exposed cohort of 3680 men (cleanup workers) and an unexposed cohort of 7631 men (population sample) were followed from 2004 to 2012 through the Population Registry and Health Insurance Fund database. Methods Morbidity in the exposed cohort compared with the unexposed controls was estimated in terms of rate ratio (RR) with 95% CIs using Poisson regression models. Results Elevated morbidity in the exposed cohort was found for diseases of the nervous system, digestive system, musculoskeletal system, ischaemic heart disease and for external causes. The most salient excess risk was observed for thyroid diseases (RR=1.69; 95% CI 1.38 to 2.07), intentional self-harm (RR=1.47; 95% CI 1.04 to 2.09) and selected alcohol-related diagnoses (RR=1.25; 95% CI 1.12 to 1.39). No increase in morbidity for stress reactions, depression, headaches or sleep disorders was detected. Conclusions No obvious excess morbidity consistent with biological effects of radiation was seen in the exposed cohort, with the possible exception of benign thyroid diseases. Increased alcohol-induced morbidity may reflect alcohol abuse, and could underlie some of the higher morbidity rates. Mental disorders in the exposed cohort were probably under-reported. The future challenge will be to study mental and physical comorbidities in the Chernobyl cleanup workers cohort.

Objectives The study demonstrates the application of a hierarchical Bayesian meta-analysis of epidemiologie studies that show an association between pancreatic cancer risk and job titles, using a job-exposure matrix to estimate risks for occupational exposure agents. Methods Altogether 261 studies published from 1969 through 1998 on pancreatic cancer and job titles were identified. When proportional studies were excluded, 77 studies were informative for 9 selected occupational agents. These studies included more than 3799 observed pancreatic cancer cases. Hierarchical Bayesian models were used for job titles (lower-level data) and agents (higher-level data), the latter from a Finnish job-exposure matrix. Non-Bayesian random effects models were applied for job titles to check consistency with the Bayesian results. Results The results suggest that occupational exposures to chlorinated hydrocarbon compounds may increase the risk of pancreatic cancer; the meta-relative risk (MRR) was 2.21 [95% credible interval (CrI) 1.31-3.68]. A suggestive weak excess was found for exposure to insecticides (MRR 1.95, 95% CrI 0.51-7.41). Conclusions Hierarchical models are applicable in meta-analyses when studies addressing the agent(s) under study are lacking or are very few, but several studies address job titles with potential exposure to these agents. Hierarchical meta-analytic models involving durations and intensities of exposure to occupational agents from a job-exposure matrix should be developed.

Objectives. The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design. The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300-500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979-2009 was compared with that of the Finnish patients outside the cohort. Methods. The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan-Meier method and Cox regression modelling. Results. There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85-1.30) and for non-Sami 1.02 (0.86-1.20), indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion. Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland.

Objectives In the 1970s and 1980s, people in a village in southern Finland had been exposed to high concentrations of chlorophenols in the drinking water and in fish from a nearby lake. An ecological analysis and a case-control study conducted around 1990 indicated significant excess in the incidence of non-Hodgkin's lymphoma and soft-tissue cancer in the municipality and a relationship between the chlorophenol exposure and the incidence of these cancers. The present article reports a follow-up of cancer risk in the same study area during a 20-year period after the closing of the old water intake plant, which was contaminated by chlorophenols. Methods The observed and expected numbers of cancer were obtained for three periods, 1953-1971 (before exposure), 1972-1986 (during exposure) and 1987-2006 (after exposure), for all cancers combined and separately for cancers potentially related to chlorophenols. Results The present study demonstrates that all of the cancer risks returned to the average population level during the 20-year period after the old water intake plant was closed and chlorophenol exposure stopped. Conclusions The rapid changes in cancer risk after changes in chlorophenol exposure suggest that chlorophenols may have a promotion effect in the carcinogenic process.

Kiuru, A., Auvinen, A., Luokkamäki, M., Makkonen, K., Veidebaum, T., Tekkel, M., Rahu, M., Hakulinen, T., Servomaa, K., Rytömaa, T. and Mustonen, R. Hereditary Minisatellite Mutations among the Offspring of Estonian Chernobyl Cleanup Workers. Radiat. Res. 159, 651–655 (2003). A single accidental event such as the fallout released from the Chernobyl reactor in 1986 can expose millions of people to non-natural environmental radiation. Ionizing radiation increases the frequency of germline mutations in experimental studies, but the genetic effects of radiation in humans remain largely undefined. To evaluate the hereditary effects of low radiation doses, we compared the minisatellite mutation rates of 155 children born to Estonian Chernobyl cleanup workers after the accident with those of their siblings born prior to it. All together, 94 de novo paternal minisatellite mutations were found at eight tested loci (52 and 42 mutants among children born after and before the accident, respectively). The minisatellite mutation rate was nonsignificantly increased among children born after the accident (0.042 compared to 0.036, OR 1.33, 95% CI 0.80–2.20). Furthermore, there was some indication of an increased mutation rate among offspring born after the accident to workers who had received doses of 20 cSv or above compared with their siblings born before the accident (OR 3.0, 95% CI 0.97–9.30). The mutation rate was not associated with the father's age (OR 1.04, 95% CI 0.94–1.15) or the sex of the child (OR 0.95, 95% CI 0.50–1.79). Our results are consistent with both no effect of radiation on minisatellite mutations and a slight increase at dose levels exceeding 20 cSv.

Chlorination of water rich in organic material is known to produce a complex mixture of organochlorine compounds, including mutagenic and carcinogenic substances. A historical cohort study of 621,431 persons living in 56 towns in Finland was conducted in order to assess the relation between historical exposure to drinking water mutagenicity and cancer. Exposure to quantity of mutagenicity was calculated on the basis of historical information of raw water quality and water treatment practices using an empirical equation relating mutagenicity and raw water pH, KMnO4value and chlorine dose. Cancer cases were derived from the population-based Finnish Cancer Registry and follow-up time in the study started in 1970. Age, gender, time period, social class, and urban residence were taken into account in Poisson regression analysis of the observed numbers of cases using expected numbers of cases standardized for age and gender as a basis. Excess risks were calculated using a continuous variable for mutagenicity for 3,000 net rev/l exposure representing an average exposure in a town using chlorinated surface water. After adjustment for confounding, a statistically significant excess risk was observed for women in cancers of the bladder (relative risk [RR] = 1.48, 95 percent confidence interval [CI] = 1.01-2.18), rectum (RR = 1.38, CI = 1.03-1.85), esophagus (RR = 1.90, CI = 1.02-3.52), and breast (RR = 1.11, CI = 1.01-1.22). These results support the magnitude of excess risks for rectal and bladder cancers found in earlier epidemiologic studies on chlorination by-products and give additional information on exposure-response concerning the mutagenic compounds. Nevertheless, due to the public health importance of water chlorination, uncertainty related to the magnitude of observed risks, and the fact that excess risks were observed only for women, the results of the study should be interpreted with caution.

Period analysis provides more up-to-date estimates of cancer patient survival than traditional methods, but there is a trade-off between up-to-dateness and precision. Our objective was to compare the performance of period and complete analysis in terms of up-to-dateness and precision of survival estimates. Five-year relative survival data actually observed for patients diagnosed with 1 of 20 common forms of cancer in Finland in 36 overlapping 5-year periods between 1958–1962 and 1993–1997 were compared with period estimates and various variants of complete estimates of 5-year relative survival potentially available during these periods. At comparable levels of up-to-dateness, survival estimates from period analysis were more precise than survival estimates from complete analysis. At comparable levels of precision, period analysis provided more up-to-date survival estimates than did complete analysis. These results further encourage more widespread use of period analysis as a standard tool for up-to-date monitoring of cancer patient survival by population-based cancer registries.

Survival from cancer over a certain time period is often measured by the 'relative survival rate'. This is the ratio of the observed survival rate in the group of patients to the survival rate expected in a group of people in the general population, who are similar to the patients with respect to all of the possible factors affecting survival at the beginning of the period, except for the disease under study. When patterns of patient withdrawal differ for a number of subgroups of patients with equal relative survival rates, the current method of derivation of the relative survival rate is biased. A method based on the concept of an 'expected life table' is proposed for removal of the bias. Examples based on material from the Finnish Cancer Registry suggest that the practical performance of the proposed method is better than that of other alternatives, even when the relative survival rates in the subgroups are not equal.