Subsequent malignant neoplasms after primary hematological malignancy in adult patients.

Patients with primary hematological malignancy (HM) are at an elevated risk of subsequent malignant neoplasms (SMNs), which is a common concern after treatment of primary cancer. We identified 45,533 patients aged ≥20 years and diagnosed with primary HM in Finland from 1992 to 2019 from the Finnish Cancer Registry and estimated standardized incidence ratios (SIR) and excess absolute risks per 1000 person-years (EAR) for SMNs. A total of 6076 SMNs were found (4604 solid and 1472 hematological SMNs). The SIRs were higher for hematological SMNs (SIR 4.9, 95% confidence interval [CI] 4.7-5.2) compared to solid SMNs (SIR 1.5, 95% CI 1.4-1.5). The SIRs for hematological SMNs were highest in the young HM patients aged 20-39 years (SIR 9.2, 95% CI 6.8-12.2 in males and SIR 10.5, 95% CI 7.2-14.7 in females) and decreased by age of first primary HM. However, EARs for hematological SMNs were highest in the older patients, aged 60-79 years at their first primary HM (EAR 5.7/1000 and 4.7/1000 in male and female patients, respectively). In conclusion, the incidence of both hematological and solid SMNs were increased in hematological cancer patients. The relative risk (SIR) was highest among younger HM patients with hematological SMNs. The absolute second cancer burden reflected by high EAR arises from solid malignancies in older patients. Our results accentuate the need for vigilance in the surveillance of HM patients.

Familial aggregation of early-onset cancers in early-onset breast cancer families.

The risk of early-onset (EO) breast cancer is known to be increased in relatives of EO breast cancer patients, but less is known about the familial risk of other EO cancers. We assessed familial risks of EO cancers (aged ≤40 years) other than breast cancer in 54 753 relatives of 5562 women with EO breast cancer (probands) by using a population-based cohort from Finland. Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) were estimated by using gender-, age- and period-specific cancer incidences of the general population as reference. The risk of any cancer excluding breast cancer in first-degree relatives was comparable to population cancer risk (SIR 0.99, 95% CI: 0.84-1.16). Siblings' children of women with EO breast cancer were at an elevated risk of EO testicular and ovarian cancer (SIR = 1.74, 95% CI: 1.07-2.69 and 2.69, 95% CI: 1.08-5.53, respectively). The risk of EO pancreatic cancer was elevated in siblings of the probands (7.61, 95% CI: 1.57-22.23) and an increased risk of any other cancer than breast cancer was observed in children of the probands (1.27, 95% CI: 1.03-1.55). In conclusion, relatives of women with EO breast cancer are at higher familial risk of certain discordant EO cancers, with the risk extending beyond first-degree relatives.

Risk of induced abortions in childhood cancer survivors.

BACKGROUND: The relative probability of pregnancy and parenthood in cancer survivors is reduced. Studies have shown that cancer survivors are concerned about the health of their offspring and the recurrence of their own cancer. This could lead to an increased risk of induced abortion. The aim of this study was to examine whether pregnancies of childhood cancer survivors (CCSs) who were 0 to 14 years old at diagnosis in 1971-2012 were more likely to result in induced abortions in comparison with population controls. METHODS: Data from Finnish registries for cancer, births, and induced abortions were merged to identify 420 first pregnancies of CCSs and 2508 first pregnancies of age-matched population controls in 1987-2013. Poisson regression and logistic regression modeling were used to estimate incidence rates and relative risks (RRs) with 95% confidence intervals (CIs) of first pregnancies and induced abortions in CCSs in comparison with population controls. RESULTS: The risk of first pregnancy was reduced in CCSs in comparison with population controls (RR, 0.72; 95% CI, 0.64-0.80), whereas the risk of a first pregnancy resulting in an induced abortion was similar in CCSs and population controls (RR, 1.01; 95% CI, 0.77-1.33). In subanalyses stratifying by decade of diagnosis and cancer treatment, the risk of induced abortion was similar in CCSs and population controls. CONCLUSIONS: Female CCSs do not have an overall increased risk of induced abortions. The reduced probability of pregnancy among CCSs highlights the continued need for interventions to preserve fertility at the time of a cancer diagnosis.

Cancer Incidence and Mortality in the Oldest Old: A Nationwide Study in Finland.

The world's population is aging rapidly. This study reports the burden of cancer in the "oldest old" (aged ≥85 years) in Finland, 1953-2017, and estimates age-specific cancer rates in the older population (65-99 years) for 1988-2017. The Finnish Cancer Registry provided data on all cancer diagnoses, cancer deaths, and other deaths in cancer patients in Finland for 1953-2017. Between 1953-1957 and 2013-2017, the proportion of incident cancers in those aged ≥85 years increased from 1.5% to 9.6% (597 to 15,360 new cases), and in 2013-2017, more new cancers were diagnosed at ages ≥85 years than ages <50 years. Cancer incidence and excess mortality attributable to cancer peaked at ages 85-94 years and declined subsequently, whereas cancer-specific mortality continued to increase or plateaued. Due to demographic changes, the number of new cancers in the oldest old has increased substantially in Finland, and currently nearly 1 in 10 cancers are diagnosed in this age group. The increasing cancer burden in the oldest old poses a major challenge for health care and needs to be addressed in designing clinical research and reporting of cancer registries. In older populations with competing risks of death, we propose excess cancer mortality as a measure of cancer-related mortality.

Familial aggregation of early-onset cancers.

This registry-linkage study evaluates familial aggregation of cancer among relatives of a population-based series of early-onset (≤40 years) cancer patients in Finland. A cohort of 376,762 relatives of early-onset cancer patients diagnosed between 1970 and 2012 in 40,538 families was identified. Familial aggregation of early-onset breast, colorectal, brain and other central nervous system (CNS) cancer and melanoma was explored by standardized incidence ratios (SIR), stratified by relatedness. Gender-, age- and period-specific population cancer incidences were used as reference. Cumulative risks for siblings and offspring of the proband up to age ≤40 years were also estimated. Almost all early-onset cancers were sporadic (98% or more). Among first-degree relatives, SIR was largest in colorectal cancer (14, 95% confidence interval 9.72-18), and lowest in melanoma (1.93, 1.05-3.23). Highest relative-specific SIRs were observed for siblings in families, where also parent had concordant cancer, 90 (43-165) for colorectal cancer and 29 (11-64) for CNS cancer. In spouses, all SIRs were at population level. Cumulative risk of colorectal cancer by age 41 was 0.98% in siblings and 0.10% in population, while in breast cancer the corresponding risks were 2.05% and 0.56%. In conclusion, early-onset cancers are mainly sporadic. Findings support high familial aggregation in early-onset colorectal and CNS cancers. Familial aggregation in multiplex families with CNS cancers was mainly attributed to neurofibromatosis and in colorectal cancer to FAP- and HNPCC-syndromes. The pattern of familial aggregation of early-onset breast cancer could be seen to support very early exposure to environmental factors and/or rare genetic factors.

The impact of socioeconomic status on stage specific prostate cancer survival and mortality before and after introduction of PSA test in Finland.

Socioeconomic status (SES) has an impact on prostate cancer (PCa) outcomes. Men with high SES have higher incidence and lower mortality of PCa versus lower SES males. PCa cases diagnosed in Finland in 1985-2014 (N = 95,076) were identified from the Finnish Cancer Registry. Information on education level (EL) was obtained from Statistics Finland. EL was assessed with three-tiered scale: basic, upper secondary and higher education. PCa stage at diagnosis was defined as localized, metastatic or unknown. Years of diagnosis 1985-1994 were defined as pre-PSA period and thereafter as post-PSA period. We report PCa-specific survival (PCSS) and relative risks (RR) for PCa specific mortality (PCSM) among cancer cases in Finland, where healthcare is 100% publicly reimbursed and inequality in healthcare services low. Men with higher EL had markedly better 10-year PCSS: 68 versus 63% in 1985-1994 and 90 versus 85% in 1995-2004 compared to basic EL in localized PCa. The RR for PCSM among men with localized PCa and higher EL compared to basic EL was 0.76(95%confidence interval (CI) 0.66-0.88) in 1985-1994 and 0.61(95%CI 0.53-0.70) in 1995-2004. Variation in PCSS and PCSM between EL categories was evident in metastatic PCa, too. The difference in PCSM between EL categories was larger in the first 10-year post-PSA period than before that but decreased thereafter in localized PCa, suggesting PSA testing became earlier popular among men with high EL. In summary, higher SES/EL benefit PCa survival both in local and disseminated disease and the effect of EL was more pronounced in early post-PSA period.

Stage-specific mortality and survival trends of prostate cancer patients in Finland before and after introduction of PSA.

BACKGROUND: The early diagnosis and right treatment strategy of localized prostate cancer (PCa) remains problematic. In order to characterize the survival of PCa patients, we compared patients' all-cause and cancer-specific mortalities between pre- and post-PSA periods by stage in Finland. MATERIAL AND METHODS: All PCa cases diagnosed in Finland between 1985 and 2013 (N = 91,329) were identified from the Finnish Cancer Registry (FCR). PCa stage at diagnosis was defined as localized, local node positive or metastasized. Standardized mortality ratios (SMRs), and relative and cause-specific survival were assessed by stage and introduction of PSA testing. The main limitation was the high proportion of men with unknown stage (28%). RESULTS: A clear decreasing trend in the SMR of PCa patients was evident when pre- and post-PSA eras were compared: for localized PCa, the SMR was 1.43 (95%CI 1.38-1.48) in 1985-1989 and 0.98 (95%CI 0.95-1.01) in 2000-2004, and for metastasized PCa, the SMRs were 4.51 (95%CI 4.30-4.72) and 3.01 (95%CI 2.89-3.12), respectively. Difference between cause-specific and relative survival was pronounced in localized PCa in post-PSA period: 10-year relative survival was 94.6% (95%CI 91.4-97.8) and cause-specific 84.2% (95%CI 82.9-85.5%). In metastasized PCa the difference was not that significant. CONCLUSIONS: From 1985 to 2009, the SMR among men diagnosed with PCa decreased significantly in Finland. Among men with localized PCa, the SMR decreased even below that of the Finnish male population. This and the increased difference between relative and cause-specific survival reflects most likely selection of men to opportunistic PSA testing. The results highlight the importance of caution in the use of PSA testing in healthy men.

Risk for congenital anomalies in offspring of childhood, adolescent and young adult cancer survivors.

Offspring of cancer survivors (CS) may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. Our population-based cohort study aimed to investigate the risk for congenital anomalies in offspring of CS compared to offspring of their siblings. Using the Finnish Cancer Registry, Central Population Register, and Hospital Discharge Register, we identified hospital contacts due to congenital anomalies in 6,862 offspring of CS (early-onset cancer between 1953 and 2004) and 35,690 offspring of siblings. Associations between congenital anomalies and cancer were evaluated using generalized linear regression modelling. The ratio of congenital anomalies in offspring of CS (3.2%) was slightly, but non-significantly, elevated compared to that in offspring of siblings (2.7%) [prevalence ratio (PR) 1.07, 95% confidence interval (CI) 0.91-1.25]. When offspring of childhood and adolescent survivors (0-19 years at cancer diagnosis) were compared to siblings' offspring, the risk for congenital anomalies was non-significantly increased (PR 1.17, 95% CI 0.92-1.49). No such increase existed for offspring of young adult survivors (20-34 years at cancer diagnosis) (PR 1.01, 95% CI 0.83-1.23). The risks for congenital anomalies were elevated among offspring of CS diagnosed with cancer in the earlier decades (1955-1964: PR 2.77, 95% C I 1.26-6.11; and 1965-1974: PR 1.55, 95% C I 0.94-2.56). In our study, we did not detect an overall elevated risk for congenital anomalies in offspring of survivors diagnosed in young adulthood. An association between cancer exposure of the parent and congenital anomalies in the offspring appeared only for those CS who were diagnosed in the earlier decades.

Family-based Bayesian collapsing method for rare-variant association study.

In this study, we analyze the Genetic Analysis Workshop 18 data to identify the genes and underlying single-nucleotide polymorphisms on 11 chromosomes that exhibit significant association with systolic blood pressure. We propose a novel family-based method for rare-variant association detection based on the hierarchical Bayesian framework. The method controls spurious associations caused by population stratification, and improves the statistical power to detect not only individual rare variants, but also genes with either continuous or binary outcomes. Our method utilizes nuclear family information, and takes into account the effects of all single-nucleotide polymorphisms in a gene, using a hierarchical model. When we apply this method to the genome-wide Genetic Analysis Workshop 18 data, several genes and single-nucleotide polymorphisms are identified as potentially related to systolic blood pressure.

Does farm environment protect against type 1 diabetes mellitus?

AIMS/HYPOTHESIS: Hygiene hypothesis has been shown valid in respect of allergies and asthma but has not been, however, sufficiently studied in relation to type 1 diabetes mellitus. This study investigates the effect of childhood farm environment on the prevalence of type 1 diabetes mellitus in Finnish children and young adults. METHODS: Data come from a questionnaire study carried out in 2007 (N = 5805). Prevalence of type 1 diabetes mellitus was analysed according to the type of the rural exposure below the age of 18 years. Associations were estimated and tested using Bayesian methods. RESULTS: Consistent suggestive evidence of the inverse association of childhood's farm environment with the occurrence of type 1 diabetes mellitus was shown, even though conclusive results were not reached. CONCLUSION/INTERPRETATION: Exposure to a broad variety of non-pathogenic environmental microorganisms during childhood might have a protective effect on type 1 diabetes mellitus. Results clearly suggest that further research is well grounded with larger samples.

BMI compared with central obesity indicators as a predictor of diabetes incidence in Mauritius.

The aim of the study was to compare BMI with waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-stature ratio (WSR) as a predictor of diabetes incidence. A total of 1,841 men and 2,104 women of Mauritian Indian and Mauritian Creole ethnicity, aged 25-74 years, free of diabetes, hypertension, cardiovascular disease, and gout were seen at baseline in 1987 or 1992, and follow-up in 1992 and/or 1998. At all time points, participants underwent a 2 h 75 g oral glucose tolerance test. Hazard ratios for diabetes incidence were estimated applying an interval-censored survival analysis using age as timescale. Six hundred and twenty-eight individuals developed diabetes during the follow-up period. Multivariable adjusted hazard ratios for diabetes incidence corresponding to a 1 s.d. increase in baseline BMI, WC, WHR, and WSR for Mauritian Indians were 1.49 (1.31-1.71), 1.58 (1.38-1.81), 1.54 (1.37-1.72), and 1.61 (1.41-1.84) in men and 1.33 (1.17-1.51), 1.35 (1.19-1.53), 1.39 (1.24-1.55), and 1.38 (1.21-1.57) in women, respectively; and for Mauritian Creoles they were 1.86 (1.51-2.30), 2.07 (1.68-2.56), 1.92 (1.62-2.26), and 2.17 (1.76-2.69) in men and 1.29 (1.06-1.55), 1.27 (1.04-1.55), 1.24 (1.04-1.48), and 1.27 (1.04-1.55) in women. Paired homogeneity tests showed that there was no difference between BMI and each of the central obesity indicators (all P > 0.05). The relation of BMI with the development of diabetes was as strong as that for indicators of central obesity in this study population.