Educational attainment in survivors of childhood cancer in Denmark, Finland, and Sweden.

BACKGROUND: Survivors of childhood cancer may face difficulties at school. We investigated whether childhood cancer affects attainment of upper secondary education, in a register-based cohort study from Denmark, Finland, and Sweden, where we limit bias from selection and participation. METHODS: From the national cancer registers, we identified all long-term survivors of childhood cancer diagnosed aged 0-14 years in 1971-2005 (n = 7629), compared them to matched population comparisons (n = 35,411) and siblings (n = 6114), using odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Overall, 6127 survivors (80%) had attained upper secondary education by age 25, compared to 84% among comparison groups. Elevated OR for not attaining this level were mainly confined to survivors of central nervous system (CNS) tumours (ORSurv_PopComp2.05, 95%CI: 1.83-2.29). Other risk groups were survivors who had spent more time in hospital around cancer diagnosis and those who had hospital contacts in early adulthood, particularly psychiatric. Survivors of all cancer types were less likely to have attained upper secondary education without delay. CONCLUSIONS: Although survivors of childhood cancer experienced delays in their education, many had caught up by age 25. Except for survivors of CNS tumours, survivors attained upper secondary education to almost the same extent as their peers.

Significant risk of second primary cancer among laryngeal squamous cell carcinoma patients even after 20 years.

BACKGROUND: Evidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe. METHODS: Patients 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. RESULTS: A 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). CONCLUSION: Patients 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.

Although prior research on the risk of second primary cancer (SPC) among laryngeal squamous cell carcinoma (LSCC) patients has been conducted in other regions, the European perspective remains notably underrepresented. Moreover, studies on the subject focusing especially on LSCC are, even globally, only a few. The present study, with over 6000 LSCC patients followed-up over six decades, consists of the largest reported cohort of LSCC patients in Europe, and with the longest follow-up. Patients with LSCC as a primary cancer have a 60% excess risk for an SPC, which remains significantly elevated even 20 years after the diagnosis of the first primary cancer, especially for those with a tobacco/alcohol-related cancer. Healthcare professionals should be aware of the SPC risk among LSCC survivors who should be counseled about this phenomenon.

Cervical, liver and stomach cancer incidence and mortality in non-Western immigrant women: a retrospective cohort study from four Nordic countries.

BACKGROUND: Cervical, liver and stomach cancers are the most common infection-associated malignancies and the leading cause of morbidity in non-Western regions. We compared the incidence and mortality of these cancers between non-Western immigrant and non-immigrant Nordic female populations. We also analysed the effect of age at immigration, duration of residence and education on cancer burden. MATERIAL AND METHODS: Study population consisted of women residents in Denmark, Finland, Iceland and Norway in 1973-2020. Non-Western women contributed 3.1% of the total 260 million person-years at risk. All women were followed from their 20th birthday, or from the date of immigration if after, until the date of their first primary cancer diagnosis, death, emigration, or the end of the country-specific study period. All data were adjusted for 10-year age groups and calendar periods, and immigrant data was further broken down by region of birth, age at immigration and education level. Country-specific estimates were produced by multivariable Poisson regression and pooled in Finland with a random effects model. RESULTS: Altogether, there were 60 982 cases of cervical, liver and stomach cancer in the study population, causing 36 582 deaths. The immigrant women had significantly higher liver (rate ratio [RR] 1.78, 95% confidence interval (CI) 1.03-3.06) and stomach cancer incidence (RR 1.68, CI 1.29-2.18), and stomach cancer mortality (RR 1.49, CI 1.17-1.92) than non-immigrant women. In the immigrant population, high education was related to lower incidence and mortality of studied cancers. The rate ratio of cervical cancer decreased with duration of residence and increased with rising age at immigration. CONCLUSION: Due to the increased incidence and mortality of infection-related cancers and changes in cancer patterns by age at immigration and duration of residence, attention should be paid to targeted health care services for immigrants. Special efforts should be given to women who have spent their youth in high-risk areas.

A population-based cohort study on changes in breast, lung and colorectal cancer incidence and mortality among non-Western immigrant women.

BACKGROUND: Cancer risk varies geographically, and migrants are influenced by different risk factors before, during and after migration. Increased migration from non-Western countries to the Nordic countries calls for a better understanding of the migrants' cancer risk and the change in risk patterns over time. The aim of this study was to compare the incidence and mortality of breast, colorectal and lung cancer between non-Western immigrant and the native female population in Denmark, Finland, Iceland, and Norway. MATERIAL AND METHODS: Data from national registries were processed and pre-analysed in each country. Multivariate Poisson regression models were used to model the relative differences in incidence and mortality as rate ratios (RR). The country-specific estimates and summary statistics were pooled together using a random effects model. RESULTS: Non-Western immigrant women had significantly lower breast (RR 0.71, 0.65-0.78), colorectal (RR 0.72, 0.57-0.92) and lung (RR 0.55, 0.42-0.72) cancer incidence rates than native women, and the risk of these cancers among immigrant women increased with duration of residence. Differences were parallel in breast, colorectal and lung cancer mortality (RR 0.64, 0.55-0.74; RR 0.66, 0.48-0.92; RR 0.51, 0.34-0.79). Among immigrant women, higher education increased the risk for breast cancer and decreased it for lung cancer. CONCLUSION: The results significantly complement and add to the previous findings of cancer burden and cancer burden transition among migrants and provide evidence of a prolonged cancer risk advantage among non-Western immigrant women. However, the findings show an increasing risk of lifestyle-related cancers with increasing duration of residence in the host country. Further studies are needed to discover underlying reasons for this phenomenon.

Income disparities between adult childhood cancer survivors and their peers-A register-based cohort study from the SALiCCS research programme.

BACKGROUND: Childhood cancer survivors face various adverse consequences. This Nordic register-based cohort study aimed to assess whether survivors of childhood cancer are more likely to have low income than their peers. METHODS: We identified 17,392 childhood cancer survivors diagnosed at ages 0 to 19 between 1971 and 2009 with 83,221 age-, sex-, and country-matched population comparisons. Annual disposable income at ages 20 to 50 years was retrieved from statistical offices (for 1990-2017) and categorized into low income and middle/high income. The number of transitions between income categories were assessed using binomial regression analyses. RESULTS: The prevalence of annual low income among childhood cancer survivors was 18.1% and 15.6% among population comparisons (risk ratio [RR] 1.17; 95% confidence interval [CI] 1.16-1.18). Compared to population comparisons, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to transition from low to middle/high income and 12% (10%-15%) more likely to transition from middle/high to low income during follow-up. Among those initially in the low income category, survivors were 7% (95% CI 3%-11%) more likely to remain in the low income category. If the initial category was middle/high income, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to remain in the middle/high income and 45% (37%-53%) more likely to transition to the low income category permanently. CONCLUSIONS: Childhood cancer survivors are at higher risk for low income in adulthood than their peers. These disparities might be reduced by continued career counseling along with support in managing within the social security system.

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.

Early-onset grade 2-3 diffuse gliomas and schwannomas increase the risk of central nervous system tumors among the patients' relatives.

Background: Central nervous system (CNS) tumors are a heterogeneous group of tumors that include several aggressive malignancies with a high mortality rate. This study aimed to evaluate the familial relative risk of CNS tumors in family members of early-onset index cases (probands) in and between diffuse glioma, non-diffuse glioma, meningioma, and other CNS tumors. Methods: We retrieved tumor data from the Finnish cancer registry and familial relationships data from the population information system. We ascertained 5408 probands diagnosed with primary CNS tumors (age ≤40 years) between 1970 and 2012 in Finland. We report the standardized incidence ratios as a measure of familial aggregation using Poisson regression. Results: The risk of early-onset diffuse glioma increased among siblings of probands with the same tumor [SIR 3.85, 95% confidence interval (CI): 1.66-7.59], with association mainly returning to grade 2-3 diffuse gliomas. Early-onset other CNS tumors were associated with an increased risk of other CNS tumors, early-onset meningioma, and late-onset diffuse glioma in 1st-degree relatives. The elevated risk of other CNS tumors was largely caused by schwannomas (SIR 59.44, 95% CI: 27.18-112.84 for 1st-degree relatives) and associated with neurofibromatosis. No tumor syndrome was associated with an increased risk of diffuse gliomas. Conclusions: The early onset of grade 2-3 diffuse gliomas is associated with an increased risk of similar tumor entities. Early-onset schwannomas dramatically increase CNS tumor risk with a broader tumor-type profile. In future studies, it would be important to identify the underlying shared hereditary factors that contribute to the development of familial diffuse gliomas.

Incidence of head and neck cancer among first-generation immigrants and their children in Finland.

INTRODUCTION: Limited data exist regarding head and neck cancer (HNC) burden among immigrants who may have distinct characteristics, and hence different incidence rates from the general population. Variations in behavioral habits, cultural lifestyle, or diet may cause variations across different subgroups. METHODS: The whole immigrant population of Finnish residents born abroad, and their children were retrieved for the years 1970-2017. First-generation immigrants are defined as individuals born abroad, excluding their children (even if born abroad). The study comprised 0.5 million first-generation immigrants and 0.3 million children, contributing to 6 million and 5 million person-years of follow-up, respectively. Standardized incidence ratios (SIR) and excess absolute risk (EAR) per 100,000 person-years at risk were calculated to quantify the risk of HNC among immigrants relative to the general Finnish population. RESULTS: The overall risk of any HNC was not increased among first-generation male immigrants (SIR 1.00, 95% CI: 0.88-1.15), but significantly elevated for cancer of the pharynx (SIR 1.56, 95% CI: 1.22-1.95), and larynx (SIR 1.38, 95% CI: 1.02-1.83) and decreased for lip (SIR 0.38, 95% CI: 0.20-0.67). The increased risk of pharyngeal cancer was highest among male immigrants from Asia Pacific (SIR 4.21, 95% CI: 2.02-7.75). First-generation immigrant women had a significantly reduced risk of any HNC (SIR 0.45, 95% CI: 0.37-0.55), which remained even after stratification by site. We observed no increased risk of any HNC among the children of first-generation immigrants. CONCLUSION: Healthcare professionals need to recognize the groups at higher HNC risk. Efforts to address the main etiological risk factors, such as smoking, are needed among the selected immigrant populations, that haven't yet reached similar decreasing trends, as in for example smoking, as the main population.NOVELTY AND IMPACTCurrently, globally, over 280 million people live outside their country of birth. Limited data exist regarding head and neck cancer (HNC) burden among immigrants who may have distinct characteristics and hence different incidence rates from the general population. Immigrant studies can provide novel data by shedding light on risk alterations and the pace of acculturation of different populations.

Use of health services one year before primary colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) patient pathways focus typically on periods after confirmed diagnosis and only limited data are available on pathways prior to cancer diagnosis. The aim of the study was to describe the use of health services (HS) one year before diagnosis among CRC patients in Finland. We also studied the role of sex, age, stage, and university hospital district in relation to the use of HS during the pre-diagnostic phase. This information is expected to bring light on the question why CRC is often not found in its early stages. METHODS: Incident CRC cases (N = 3115) concerning year 2015 were retrieved from the Finnish Cancer Registry and linked with data from the Finnish Institute for Health and Welfare on primary or specialised care outpatient visits or inpatient episodes over one year prior to CRC diagnosis. We modelled the average number of HS events per patient using Poisson regression model with log-link. Change points for monthly HS event rates and 95% CIs one year before diagnosis were evaluated using Poisson broken line regression models. RESULTS: Around 10% of patients diagnosed in 2015 had no events prior to cancer leaving 2816 CRCs in the study. Of all pre-diagnostic events (N = 23268), 86% were outpatient events and 14% inpatient episodes. More than half of the inpatient episodes (65%) started as urgent admissions. The use of HS started to increase 3-4 months before diagnosis. The average number of pre-diagnostic HS events per patient varied by sex, age, stage and university hospital district. Overall, men had more events per patient than women and older patients had more events than younger patients. CONCLUSIONS: The amount of inpatient episodes starting as urgent admissions indicate potential bottlenecks in the access to health services. An increase in service use only 3-4 months prior to diagnosis reflects a need for advice both for health care professionals and the general population in recognising symptoms of CRC.

Sexually transmitted diseases in cancer patients diagnosed under the age of 20 years - a national registry-based cohort study from Finland.

BACKGROUND: Adolescents with chronic diseases are shown to be vulnerable for risky sexual behavior. Childhood cancer patients seem to engage in risky health behaviors as frequently as general population, but little is known about sexual issues in this group of patients. MATERIAL AND METHODS: We characterized the risk for sexually transmitted diseases (STD) in a Finnish population-based cohort of over 6,000 childhood cancer patients diagnosed with cancer under the age of 20 years between 1971 and 2009, compared with over 30,000 age- and sex -matched population comparisons. The data were constructed through linkage between national cancer, population, infectious diseases, and hospital discharge registries. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression modeling with attained age as the underlying time scale. RESULTS: Childhood cancer patients had a decreased risk for having an infection with chlamydia, the most common STD in our cohort, when comparing with population comparisons (HR 0.77, 95% CI 0.69-0.86). The risk was lowest among male patients (HR 0.64, 95% CI 0.53-0.79) and patients with central nervous system (CNS) tumors (HR 0.46, 95% CI 0.33-0.63). The overall risk for cervical dysplasia was slightly increased among female cancer patients when compared with their population comparisons (HR 1.28, 95% CI 1.02-1.60). Greatest risk elevation was found among patients diagnosed with cancer in ages 10-14 years (HR 2.31, 95% CI 1.46-3.65) and patients with lymphoma (HR 1.95, 95% CI 1.20-3.16). The risk for all explored outcomes seemed to be decreased among patients with CNS tumors. CONCLUSIONS: Our findings highlight the importance of integrating sexual issues as a part of psychosocial support and having a systematic transition program in the follow-up care of childhood cancer patients.

Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden: a register-based cohort study from the SALiCCS research programme.

BACKGROUND: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population. METHODS: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer. FINDINGS: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3-16·5) for childhood cancer survivors, 14·0% (13·5-14·5) for siblings, and 12·7% (12·4-12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31-1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28-1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals. INTERPRETATION: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors. FUNDING: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation.

Employment status and occupational positions of childhood cancer survivors from Denmark, Finland and Sweden: A Nordic register-based cohort study from the SALiCCS research programme.

BACKGROUND: A childhood cancer diagnosis and late effects of treatment may affect survivors' possibilities of employment or highly skilled occupations later in life. In this study, we compared the employment and occupational status of childhood cancer survivors with population comparisons and siblings. METHODS: In a cohort study based on Nordic registers, we identified 10 461 survivors of childhood cancer diagnosed before age 20 years in Denmark, Finland and Sweden since 1971. Survivors were compared with 48 928 population comparisons matched to survivors by age, sex and geographical region and 12 605 siblings of survivors. Annual outcome information on employment, unemployment, health-related unemployment and occupational position was obtained from the statistical institutes between 1980-2017 and assessed in multivariate logistic regression analyses from age 30 onwards. FINDINGS: By 30 years of age, 9.2% (95% CI, 8.6-9.9%) of survivors were unemployed for health reasons. Childhood cancer survivors had considerably higher odds of health-related unemployment at ages 30, 40 and 50 than population comparisons (ORage30, 2.57; 95% CI, 2.35-2.81) and siblings (ORage30, 2.50; 95% CI, 2.15-2.90). We observed no large difference in unemployment unrelated to health or in occupational position. Health-related unemployment was particularly pronounced among survivors of central nervous system tumours and survivors diagnosed below 15 years of age. INTERPRETATION: Survivors at risk of health-related unemployment should be offered comprehensive survivorship care and interventions for obtaining and maintaining suitable employment. FUNDING: NordForsk [76111], the Danish Childhood Cancer Foundation [2016-0293], Aarhus University [43239402], the Swedish Childhood Cancer Foundation [PR2020-0130] and [OB2019-0003], Tømrermester Jørgen Holm og Hustru Elisa F. Hansens Mindelegat [20088] and the Swiss National Science Foundation to LM [P2LUP3_175288].

Cohort Profile: The Socioeconomic Consequences in Adult Life After Childhood Cancer in Scandinavia (SALiCCS) Research Programme.

INTRODUCTION: The growing number of survivors of childhood cancer, with many years of life ahead, demonstrates the increasing clinical and public health relevance of investigating the risks of social and socioeconomic impairment after a childhood cancer diagnosis and the life-saving treatment. To enrich understanding of the mental, social and socioeconomic difficulties that childhood cancer survivors may face during their life-course, identify particularly vulnerable survivors and overcome the limitations of previous research, we initiated the Socioeconomic Consequences in Adult Life after Childhood Cancer in Scandinavia (SALiCCS) research programme. METHODS: This Nordic cross-border research programme is a collaboration between the Danish Cancer Society, the Finnish Cancer Registry and Karolinska Institutet to investigate a broad range of mental, social and socioeconomic conditions in long-term childhood cancer survivors in Denmark, Finland and Sweden. SALiCCS is based on a registry-based matched cohort design, comprising five-year survivors of cancer diagnosed at ages 0-19 years (1971-2008 in Denmark, 1971-2009 in Finland, 1971-2011 in Sweden), age-, sex- and country-matched population comparisons and sibling comparisons who were followed over time. Outcomes of interest included mental disorders, educational achievements, employment and profession, family life and the need of social security benefits. Individual-level data linkage among various national registries provided the data for the research programme. RESULTS: The SALiCCS core population comprises 21,292 five-year survivors, 103,303 population comparisons and 29,644 siblings as a second comparison group. The most common diagnoses in survivors were central nervous system tumours, leukaemias and lymphomas. DISCUSSION: SALiCCS is the largest, most comprehensive population-based research initiative in this field, based on high-quality registry data with minimal risk of bias. The findings will be informative for evidence-based survivorship care targeting not only somatic late effects but also psychosocial impairments.

Familial aggregation of early-onset haematological malignancies.

Population-based studies on familial aggregation of haematological malignancies (HM) have rarely focused specifically on early-onset HMs. We estimated standardized incidence ratios (SIR) and cumulative risks of relatives with Hodgkin lymphoma (HL), non-Hodgkin lymphomas (NHL), acute lymphoblastic leukaemia/lymphoma (ALL/LBL) and acute myeloid leukaemia (AML) when index persons and relatives were diagnosed with early-onset HM. A total of 8791 patients aged ≤40 years and diagnosed with primary HM in Finland from 1970 to 2012 were identified from the Finnish Cancer Registry and their 75 774 family members were retrieved from the population registry. SIRs for concordant HMs were elevated among first-degree relatives in all of the most common HMs of children and adolescents and young adults (AYA). The risk was highest among siblings with HL (SIR 9·09, 95% confidence interval 5·55-14·04) and AML (8·29, 1·00-29·96). HL also had the highest cumulative risk for siblings at ≤40 years of age (0·92% vs. 0·11% in the population). In conclusion, significantly elevated SIRs indicate a role of shared aetiological factors in some families, which should be noted in the clinical setting when caring for patients with early-onset HMs.

Familial aggregation of testicular cancer among early-onset cancer survivors. A prospective observational cohort data from Finland.

Testicular cancer (TC) is the most common form of cancer in men aged 15-35 years. Familial risk for TC is among highest of all cancers. MATERIAL AND METHODS: A prospective observational cohort of 9111 relatives in 2,188 families of early-onset TC patients, called probands, diagnosed at age ≤40 years in Finland between 1970 and 2012. Standardized incidence ratios (SIR) were used as measures of familial aggregation for early-onset (≤40 years) TC. Follow-up ended at diagnosis of TC, death or 31 December 2014 whichever earliest. RESULTS: Among first-degree relatives of early-onset TCs, in all 12 early-onset TC cases (0.24%) were diagnosed over the follow-up; the SIR for any first-degree relative was 4.59 (95% confidence interval (CI): 2.37-8.01) and for brothers the SIR was 6.51 (95% CI 3.12-11.96). DISCUSSION: Familial aggregation of TC shows substantial risk for early-onset TC among first-degree relatives of early-onset TC patients in Finland. This is important to acknowledge to avoid diagnostic delay especially of TC.

Linking population-based registries to identify familial cancer risk in childhood cancer.

BACKGROUND: Linked population-based registries provide a unique source for identification of new family cancer syndromes and for elucidating risk of early-onset cancer in close relatives of cancer patients. METHODS: Using the Finnish Cancer Registry, we identified 9078 probands who had been diagnosed with cancer at <21 years of age between 1970 and 2012. Siblings, offspring, parents, nephews, and nieces of probands were identified from the Population Registry. Childhood and young adult (ChYA) cancer diagnoses (age 0-39 years) in relatives were identified by linking to the Finnish Cancer Registry. The relative risk of ChYA cancer in family members of probands was estimated using standardized incidence ratios (SIRs). RESULTS: Among 58,010 family members of the 9078 probands, 363 ChYA cancers were diagnosed, 324 of which were expected (SIR, 1.12; 95% CI, 1.01-1.24). The risk of ChYA cancer was elevated both in offspring (SIR, 2.25; 95% CI, 1.51-3.24) and in siblings (SIR, 1.17; 95% CI, 1.01-1.36). Offspring of probands with retinoblastoma were at highest risk (SIR, 75.85; 95% CI, 32.75-149.45); risks were also elevated for siblings of probands with lymphoma (SIR, 1.62; 95% CI, 1.14-2.25). Known cancer predisposition syndromes were observed in 29 (66%) of 44 sibling pairs with cancers diagnosed at <21 years of age and in 20% of the 135 families with a childhood cancer proband whose sibling was diagnosed with a young adult malignancy. CONCLUSION: Linked population-based registry data indicate a modestly increased risk of ChYA in relatives of children with cancer. Some of the observed cancer clusters in the cohort suggest novel patterns and familial cancer syndromes.

Use of fertility drugs in early-onset female cancer survivors-A Finnish register-based study on 8,929 survivors.

Advances in multimodality cancer treatments have increased the risk of long-term complications in early-onset cancer survivors. For female cancer survivors, these include diminished reproductive function, often resulting in a narrowed fertile window. The aim of our study was to evaluate the use of fertility treatments in cancer survivors (aged 0-39 years at diagnosis) compared to siblings. Data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8,929 survivors and 9,495 siblings without previous deliveries. Fertility drug purchases from 1993 to 2012 at the age of 16-41 years were included. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for the use of fertility drugs, adjusting for age and calendar time at fertility drug purchase. Fertility treatments were more common in survivors compared to siblings, as 6.1% of survivors compared to 3.8% of siblings had bought fertility drugs (IRR 1.43, 95% confidence interval [CI] 1.25-1.65). A subclassification of fertility treatments into ovulation inductions and assisted reproductive technology (ART), showed increased use of ART (IRR 2.41, 95% CI 1.97-2.96), whereas the use of ovulation induction was similar in survivors and siblings. Analyses by calendar time periods showed the use of ART to be significantly higher in the most recent decade, from 2003 onwards. We conclude that cancer survivors have an increased risk for subfertility, which is why fertility counseling is important. However, our results mirror a more active approach among clinicians towards fertility treatments in cancer survivors during the most recent years.

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.

Maternal diabetes and risk of childhood cancer in the offspring.

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.

Vasectomy and the risk of prostate cancer in a Finnish nationwide population-based cohort.

INTRODUCTION & OBJECTIVES: There are conflicting reports on the association of vasectomy and the risk of prostate cancer (PCa). Our objective was to evaluate the association between vasectomy and PCa from a nationwide cohort in Finland. MATERIALS & METHODS: Sterilization registry of Finland and the Finnish Cancer Registry data were utilized to identify all men who underwent vasectomy between years 1987-2014 in Finland. Standard incidence ratio (SIR) for PCa as well as all-cause standardized mortality ratios (SMR) were calculated. RESULTS: We identified 38,124 men with vasectomy with a total of 429,937 person-years follow-up data. The median age at vasectomy was 39.7 years (interquartile range [IQR] 35.9-44.0), after vasectomy PCa was diagnosed in 413 men (122 cases 0-10 years, 219 cases 10-20 years and 72 cases >20 years from vasectomy). SIR for PCa for the vasectomy cohort was 1.15 (95% CI: 1.04-1.27). By the end of follow-up, 19 men had died from PCa, while the expected number was 20.5 (SMR 0.93 [95%CI: 0.56-1.44]). The overall mortality was decreased (SMR 0.54 [95%CI: 0.51-0.58]) among men with vasectomy. CONCLUSION: We found a small statistically significant increase in PCa incidence after vasectomy, but in contrast the mortality of vasectomized men was significantly reduced. This may be due to higher likelihood of vasectomized men to undergo prostate-specific antigen testing, having healthier general lifestyle and other biological factors e.g. high reproductive fitness.