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.

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.