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 (Peer reviewe

Breast cancer in neurofibromatosis type 1 : overrepresentation of unfavourable prognostic factors

Background: An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers. Methods: The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls. Results: A total of 32 breast cancers were diagnosed in 1404 NF1 patients during the follow-up. Women with NF1 had an estimated lifetime risk of 18.0% for breast cancer, and this is nearly two-fold compared with that of the general Finnish female population (9.74%). The 26 successfully retrieved archival NF1 breast tumours were more often associated with unfavourable prognostic factors, such as oestrogen and progesterone receptor negativity and HER2 amplification. However, survival was worse in the NF1 group (P = 0.053) even when compared with the control group matched for age, diagnosis year, gender and oestrogen receptor status. Scrutiny of The Cancer Genome Atlas data set showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population. Conclusions: These results emphasise the role of the NF1 gene in the pathogenesis of breast cancer and a need for active follow-up for breast cancer in women with NF1.Peer reviewe

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia : The CREAM Consortium

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).Peer reviewe

Work-related stress in midlife is associated with higher number of mobility limitation in older age-results from the FLAME study

The aim of this study is to investigate whether work-related stress symptoms in midlife are associated with a number of mobility limitations during three decades from midlife to late life. Data for the study come from the Finnish Longitudinal Study of Municipal Employees (FLAME). The study includes a total of 5429 public sector employees aged 44-58 years at baseline who had information available on work-related stress symptoms in 1981 and 1985 and mobility limitation score during the subsequent 28-year follow-up. Four midlife work-related stress profiles were identified: negative reactions to work and depressiveness, perceived decrease in cognition, sleep disturbances, and somatic symptoms. People with a high number of stress symptoms in 1981 and 1985 were categorized as having constant stress. The number of self-reported mobility limitations was computed based on an eight-item list of mobility tasks presented to the participants in 1992, 1997, and 2009. Data were analyzed using joint Poisson regression models. The study showed that depending on the stress profile, persons suffering from constant stress in midlife had a higher risk of 30-70 % for having one more mobility limitation during the following 28 years compared to persons without stress after adjusting for mortality, several lifestyle factors, and chronic conditions. A less pronounced risk increase (20-40 %) was observed for persons with occasional symptoms. The study suggests that effective interventions aiming to reduce work-related stress should focus on both primary and secondary prevention