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.
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.
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.
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.
Twin studies have been adopted for decades to disentangle the relative genetic and environmental contributions for a wide range of traits. However, heritability estimation based on the classical twin ...models does not take into account dynamic behavior of the variance components over age. Varying variance of the genetic component over age can imply the existence of gene-environment (G×E) interactions that general genome-wide association studies (GWAS) fail to capture, which may lead to the inconsistency of heritability estimates between twin design and GWAS. Existing parametricG×Einteraction models for twin studies are limited by assuming a linear or quadratic form of the variance curves with respect to a moderator that can, however, be overly restricted in reality. Here we propose spline-based approaches to explore the variance curves of the genetic and environmental components. We choose the additive genetic, common, and unique environmental variance components (ACE) model as the starting point. We treat the component variances as variance functions with respect to age modeled by B-splines or P-splines. We develop an empirical Bayes method to estimate the variance curves together with their confidence bands and provide an R package for public use. Our simulations demonstrate that the proposed methods accurately capture dynamic behavior of the component variances in terms of mean square errors with a data set of >10,000 twin pairs. Using the proposed methods as an alternative and major extension to the classical twin models, our analyses with a large-scale Finnish twin data set (19,510 MZ twins and 27,312 DZ same-sex twins) discover that the variances of the A, C, and E components for body mass index (BMI) change substantially across life span in different patterns and the heritability of BMI drops to ∼50% after middle age. The results further indicate that the decline of heritability is due to increasing unique environmental variance, which provides more insights into age-specific heritability of BMI and evidence ofG×Einteractions. These findings highlight the fundamental importance and implication of the proposed models in facilitating twin studies to investigate the heritability specific to age and other modifying factors.
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.
This study indicates that childhood cancer survivors are not more likely than population controls to terminate their pregnancies by choice. They do, however, have a reduced probability of first pregnancy in comparison with population controls.
An association between maternal diabetes, its medication and childhood cancer has not been previously explored in a registry‐based setting. With a case–control design, we aimed to explore whether ...maternal diabetes is associated with an increased risk of childhood cancer in the offspring. Combining data from population‐based registries, we analyzed a total of 2,029 cases, that is, persons with childhood cancer diagnosed under the age of 20 years between years 1996–2014 and a total of 10,103 matched population controls. The mothers of the cases/controls and their diagnoses of diabetes (DM) before/during pregnancy as well as their insulin/metformin prescriptions during pregnancy were identified. Conditional logistic regression modeling was used to analyze the risk of childhood cancer. The OR for childhood cancer among those exposed to any maternal diabetes was 1.32 (95% CI 1.14–1.54) compared to the offspring of the nondiabetic mothers. The effect of maternal diabetes on the risk of childhood cancer remained elevated even after adjusting for maternal age, parity and smoking. Our data suggest that maternal diabetes medication may reduce the risk for childhood cancer (adjusted OR 0.83, 95% CI 0.36–1.94), especially in gestational diabetes (adjusted OR 0.26, 95% CI 0.05–1.25), compared to the diabetic mothers without medication. The risk of childhood leukemia was significantly higher among children exposed to any maternal diabetes (OR 1.36, CI 1.04–1.77) compared to the unexposed. Maternal diabetes appears to be associated with an increased risk of childhood cancer in the offspring. The possible risk‐reducing effect of an exposure to diabetes medication on offspring cancer risk warrants further investigation.
What's new?
Only a small fraction of early‐onset childhood cancers are linked to hereditary factors, suggesting that perinatal exposures, particularly in the mother, significantly impact childhood cancer risk. A potentially important, though understudied risk factor is maternal diabetes. This investigation of nationwide population‐based registry data shows that maternal diabetes is associated with an elevated risk of childhood cancer in offspring. Offspring born to mothers diagnosed with gestational diabetes were at increased risk of childhood leukemia and certain solid tumors in particular. Further investigation is needed to determine whether diabetes medications taken during pregnancy can reduce cancer risk in offspring.
BACKGROUNDEvidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe.METHODSPatients diagnosed with primary LSCC ...from 1953-2018 were retrieved from the Finnish Cancer Registry. A total of 6241 LSCC patients were identified adding to 49,393 person-years (PY) of follow-up until the end of 2019. Only one patient emigrated and was lost to follow-up. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population. Only non-laryngeal SPCs diagnosed six months after diagnosis of primary LSCC were included.RESULTSA SPC was diagnosed in 1244 LSCC patients (20% of all LSCC patients) over the 65-year period, predominantly in men (92%, n = 1170). Out of all SPCs, 34% were diagnosed within 0.5 to 5 years and 66% after 5 years from primary LSCC. Among male patients, the overall SIR for SPC at any location was 1.61 (95% CI: 1.52-1.71), corresponding to 9.49 excess SPCs per 1000 PYR (95% CI: 8.19-11). The corresponding SIR for women was 1.47 (95% CI: 1.15-1.84), yielding 4.82 excess SPCs per 1000 PYR (95% CI: 2.36-9.84). The risk remained significant even after 20 years of follow-up (SIR for all 1.73, 95% CI: 1.49-2.01 and EAR 16.8 per 1000 PY, 11.88-23.75). The risk for SPC was also significantly elevated in all age groups, except <40. The highest SIRs were for SPCs arising in the mouth/pharynx (SIR for all 3.08, 95% CI: 2.36-3.95 and EAR 0.80 per 1000 PY, 0.55-1.15) and lungs (3.02, 2.75-3.30 and 5.90 per 1000, 5.13-6.78).CONCLUSIONPatients with LSCC as primary cancer have a 60% excess risk for an SPC, especially for tobacco-associated cancers, remaining significantly elevated even decades after treatment.
Background
The incidence and survival of oral squamous cell carcinoma (OSCC) patients have increased in recent years. Understanding their long‐term survival aspects is essential for optimal treatment ...and follow‐up planning. Almost one in five cancers diagnosed occurs nowadays in individuals with a previous diagnosis of cancer.
Methods
Patients diagnosed with primary OSCC during 1953‐2015 were retrieved from the Finnish Cancer Registry. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person‐years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population.
Results
Among 6602 first primary OSCC patients there were 640 (10%) SPCs. The SIR for SPCs was 1.85 (95% CI: 1.71‐1.99, P < .001) corresponding to an EAR of 8.78 (95% CI: 7.29‐10.26).
Conclusions
Health care professionals should be aware of the second primary cancer risk after management of primary OSCC and patients need to be counseled about this phenomenon.
The authors report that the labels indicating the symptom types and no symptom lines in the original version of Figure 2 were missing. The correct version of Figure 2 with the labels included is ...provided below.
Recent studies have shown that some four in ten cancers are attributable to a few key risk factors. The aim of this study was to estimate cohort-based population attributable fractions (PAFs) in ...Finland for potentially modifiable cancer risk factors.
Data from eight health studies including 253,953 subjects with 29,802 incident malignant solid tumors were analysed using Bayesian multivariate regression model with multiplicative risk factor effects. We estimated the effects of smoking, excess body weight, alcohol consumption, physical activity, parity and education on cancer incidence and related PAFs by cancer site, accounting for competing mortality.
PAF for all cancer sites and exposures combined was 34% (95% credible interval 29%−39%) in men and 24% (19%−28%) in women. In men, 23% (21%−27%) and in women 8% (6%−9%) of all cancers were attributed to smoking. PAF related to excess body weight was 4% (2%−6%) in men and 5% (2%−7%) in women, to alcohol 7% (3%−10%) in men and 4% (0%−7%) in women, and to excess body weight and alcohol combined 10% (6%−15%) in men and 9% (4%−13%) in women.
Smoking was the most important factor contributing to cancer burden in Finnish men and women over the last 40 years. The contribution of excess body weight and alcohol consumption together outweighed the role of smoking in women. As the prevalence of overweight is expected to increase, more efficient public health measures supporting adherence to healthy weight are essential to reduce cancer burden.
•We estimated the fractions of cancers attributable to key lifestyle risk factors.•The key factors were responsible for 34% of all cancers in men and 24% in women.•10% of cancers were attributable to overweight and alcohol use together.•Overweight and alcohol use together outweighed the role of smoking in women.•Supporting healthy weight is essential to reduce future cancer burden.
The trends in incidence of lung cancer in never smokers are unclear as well as the significance of risk factors. We studied time trends in the incidence and risk factors of lung cancer in never ...smokers in Finland in a large, pooled cohort. We pooled data from seven Finnish health cohorts from the period between 1972 and 2015 with 106 193 never smokers. The harmonised risk factors included education, alcohol consumption, physical activity, height and BMI. We retrieved incident lung cancers from the nation‐wide Finnish Cancer Registry. We estimated average annual percent change (AAPC) and the effects of risk factors on cause‐specific hazard ratios (HRs) of lung cancer using Poisson regression. We detected 47 lung cancers in never smoking men (n = 31 859) and 155 in never smoking women (n = 74 334). The AAPC of lung cancer incidence was −3.30% (95% confidence interval CI: −5.68% to −0.88%, P = .009) in never smoking men and 0.00% (95% CI: −1.57% to 1.60%, P = .996) in never smoking women. Of the five studied risk factors only greater height in women had a statistically significant increased risk of lung cancer (multivariate HR = 1.84, 95%CI: 1.08 to 3.12). It is plausible that tobacco control measures focused on working places have reduced passive smoking among men more than among women, which could explain the declining trend in lung cancer incidence in never smoker men but not in never smoker women. As tobacco control measures have not been targeted to domestic environments, it is likely that women's exposure to passive smoking has continued longer.
What's New
The incidence trends and risk factors of lung cancer in never smokers remain unclear. In a harmonised population‐based cohort of 106,193 never smokers, here the authors found a decreasing trend of lung cancer incidence in men and no trend in women. Among several possible risk factors including education, alcohol consumption, physical activity, height, and body mass index, the results confirmed the association between greater height and lung cancer risk in women. As tobacco control measures have only targeted working and not domestic environments, it is plausible that women's exposure to passive smoking has continued for a longer time than men's exposure.
Abstract Background The Finnish Cancer Registry (FCR) has collected population-based data on cancer incidence for scientific research and statistical purposes since 1953. Our aim was to provide a ...comprehensive quality assessment of the current cancer registry data in Finland. Methods We used established quantitative and semi-quantitative techniques to address four main dimensions of data quality: completeness, comparability, validity and timeliness for the period 1953–2013, with a special focus on cancers diagnosed in 2009–2013. For completeness, hospital admissions and outpatient visits were used as an independent data source. Results In 2009–2013, 153 147 incident tumours were registered in the FCR. Of them, 91% were solid tumours. The completeness for all solid tumours was estimated at 96%, and for non-solid tumours at 86%. Potential underreporting was most prominent for tumours which are not typically histologically verified such as haematological malignancies and non-malignant tumours of the central nervous system. Of all cancers, 93% were morphologically verified, with variation by primary site. The proportion of cancers with uncertain or ill-defined primary site and the proportion of death certificate only registrations were both low at 1.9% and 2.6%, respectively. Conclusions The FCR provides overall accurate and close to complete national cancer data for solid malignant tumours. Registration of tumours with no histology is still compromised. This warrants continuous communication with clinicians to ensure undisturbed data flow, and active trace-back using external data sources such as hospital administrative data. In addition, broad diagnosis categories would be less sensitive to diversity of input and data quality when international comparisons are made.
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