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Background: Children experience a higher risk of psychiatric problems when their parents are diagnosed with cancer. However, the psychological effect among offspring who are born after parental cancer diagnosed in childhood or adolescence is unknown. We aimed to investigate the risk of psychiatric disorders in children of survivors with childhood or adolescent central nervous system (CNS) tumors., Methods: By combining several nationwide Swedish registers, we identified all children who had at least one parent previously diagnosed with CNS tumor below the age of 20. Five children without parental CNS tumor were randomly selected for the matching. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence interval (CI)., Results: The incidence rate of psychiatric disorders was 8.46 per 1000 person-years in children of CNS tumor survivors, whereas the rate was 7.47 in the matched comparisons, yielding an adjusted HR of 1.10 (95% CI = 0.94, 1.28). Boys of survivors had a higher risk of psychiatric disorders (adjusted HR = 1.29, 95% CI = 1.04, 1.59). The risk of the specific types of psychiatric disorders in children of tumor survivors was comparable with that in the matched comparisons, except for mental retardation. Children of survivors experienced 2.36 times higher risk of mental retardation (95% CI = 1.21, 4.58), mainly of mild mental retardation (adjusted HR = 2.99, 95% CI = 1.40, 6.38)., Conclusion: Children of survivors with CNS tumor in early life did not experience a significantly increased risk of overall psychiatric disorders, with the exception of an elevated risk of mental retardation that was mainly mild., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Autoimmune diseases are characterized by the irregular functioning of the immune system that leads to the loss of tolerance to self-antigens. The underlying nature of autoimmune diseases has led to speculation that the risk of malignancy might be higher or lower in patients with such diseases. However, the rarity and heterogeneity of both autoimmune diseases and malignancies is the main challenge for systematic exploration of associations between autoimmune diseases and cancer. The nationwide usages of electronic health records in Sweden and other countries has created longitudinal clinical datasets of large populations, which are ideal for quantifying the associations as well as possible guidance concerning the underlying mechanisms. In this report, we firstly summarize the population-based epidemiological association studies between autoimmune diseases and subsequent hematological malignancies using data derived mainly from Swedish nationwide data. These include over one million cancer cases and approximately 500,000 patients with medically diagnosed autoimmune disease. We further discuss the underlying mechanisms that contribute to the observed association between autoimmune diseases and hematological malignancies, including shared genetics, environmental factors, medical treatments of autoimmune diseases as well as dysregulated immune function., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Body height has been associated with an increased risk of venous thromboembolism (VTE), but the association can be confounded with shared familial factors (genetic/environmental). A cosibling design is useful for deeper understanding about the relationship between VTE and height., Methods and Results: From Swedish national registry databases, we used a corelative design with full siblings alongside a general Swedish population sample. A cohort of male conscripts (n=1 610 870), born in 1951 to 1992 without previous VTE, was followed from enlistment (1969-2010) until 2012. Another cohort of first-time pregnant women (n=1 093 342) from the medical birth register, without previous VTE, was followed from first pregnancy (1982-2012) until 2012. Using the Multi-Generation Register, we identified all full-sibling pairs discordant for height. This cosibling design allowed for adjustment for familial factors (genetic/environmental). Compared with the tallest women (>185 cm) and men (>190 cm), there was a graded decreased risk by lower height for both men and women. The risk was lowest in women and men with the shortest stature (<155 and <160 cm, respectively): hazard ratios=0.31 (95% confidence interval, 0.22-0.42) and 0.35 (95% confidence interval, 0.22-0.55), respectively. There was a graded association also in the cosibling design comparing siblings with varying degree of discordance for height (reference was the taller sibling): ≥10 cm difference between brothers hazard ratios=0.69 (95% confidence interval, 0.61-0.78) and sisters hazard ratios=0.65 (95% confidence interval, 0.52-0.80), respectively., Conclusions: Height is an independent predictor of VTE. The use of sibling pairs reduces the likelihood that familial confounding explains the results. The findings are important for the understanding of the pathogenesis of VTE., (© 2017 American Heart Association, Inc.)

Background and Aims: Pharmacotherapy can be an important part of the continuum of care for alcohol use disorder (AUD). The Swedish universal health-care system emphasizes provision of care to marginalized groups. The primary aim was to test associations of neighborhood deprivation and disadvantaged social status with receipt of AUD pharmacotherapy in this context., Design: Data from linked population registers were used to follow an open cohort over 7 years., Setting: Sweden., Participants: Alcohol-related ICD-10 codes reported for all hospitalizations in the Swedish Hospital Discharge Register and all clinic/office visits in the Outpatient Care Register between 2005 and 2012 were used to identify 62 549 cases with AUD., Measurements: The primary outcome was any AUD pharmacotherapy (naltrexone, disulfiram, acamprosate, nalmefene) picked up by patients between 2005 and 2012 (versus none), based on the Swedish Prescribed Drug Register. Neighborhood deprivation was defined using aggregated data from the Total Population Register; indicators of disadvantaged social status (income, education, country of origin) also came from this source., Findings: Approximately half the cases (53.7%) picked up one or more AUD pharmacotherapy prescriptions. In adjusted models, people living in neighborhoods with moderate [odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.86, 0.95] or high levels of deprivation (OR = 0.75, 95% CI = 0.70, 0.79) compared with low deprivation, those with lower incomes (for example, lowest quartile: OR = 0.70, 95% CI = 0.66, 0.73 compared with highest) and less education (for example, < 10 years: OR = 0.82, 95% CI = 0.78, 0.85 compared with 12+ years) and people born outside Sweden (OR = 0.74, 95% CI = 0.71, 0.78 compared with Swedish-born) were significantly less likely to pick up a prescription for AUD pharmacotherapy during the study period., Conclusions: There appear to be socio-economic disparities in the receipt of pharmacotherapy for alcohol use disorder in Sweden., (© 2017 Society for the Study of Addiction.)

Aim: Caloric restriction has been found to be protective against the development of type 2 diabetes mellitus (T2D) in experimental animal studies. However, studies examining this association in humans are limited. In the present study, we examined whether individuals with anorexia nervosa, one marker of severe caloric restriction in humans, have a low incidence of T2D by using several Swedish registries., Methods: Individuals with anorexia nervosa were identified from the Swedish Hospital Discharge Register and Outpatient Register between 1964 and 2010. Standardized incidence ratios (SIRs) for T2D were studied among individuals with anorexia nervosa compared to those without the disorder., Results: A total of 17,135 individuals were identified with anorexia nervosa in Sweden. From this tally, 34 of them developed T2D, demonstrating a reduced risk of T2D with a SIR of 0.70, compared to individuals without anorexia nervosa. Patients with severe anorexia, indicated by more frequent hospitalizations, had a statistically non-significant lower incidence of T2D than those with fewer hospitalizations. A sibling study, controlled for familial confounding, found a statistically non-significant association between anorexia nervosa and T2D., Conclusion: Our study found that severe caloric restriction by using individuals with anorexia nervosa as a proxy was negatively associated with T2D, which might provide a biological basis for the primary prevention of T2D. Further studies are needed to explore whether moderate caloric restriction can effectively prevent the development of T2D in general population.

Moderate alcohol consumption has been suggested to protect against venous thromboembolism (VTE). However, it is not known how alcohol abuse and its associated somatic complications affect the risk of VTE. The present study determined the risk of pulmonary embolism (PE) and deep vein thrombosis (DVT) of the lower extremities in patients with alcohol use disorders (AUDs) in Sweden. All inpatients with AUDs in 2002-2010 without a previous VTE event (72,024 patients) were matched to five controls without AUD and followed until the end of follow-up (December 31, 2010), death, emigration or a VTE event. Cox regression was used to determine adjusted hazard ratios (HRs) for VTE. AUD patients were further divided into those without alcohol-related somatic complications (AUD-) and those with alcohol-related somatic complications (AUD+, i.e., encephalopathy, epilepsy, polyneuropathy, myopathy, cardiomyopathy, gastritis, liver disease, acute pancreatitis, and chronic pancreatitis). The adjusted HR for VTE was significantly increased for both AUD- (HR 1.70, 95 % CI 1.55-1.87) and AUD+ (HR 1.73, 95 % CI 1.37-2.19) patients. The risk of DVT was increased in both AUD+ and AUD- patients (HR 1.62, 95 % CI 1.45-1.83 and HR 1.99, 95 % CI 1.53-2.59, respectively). However, the risk of PE was only significantly increased in AUD- patients (HR 1.87, 95 % 1.59-1.20) and not in AUD+ patients (HR 1.16, 95 % 0.70-1.91). In conclusion, the present study shows that AUD increases the risk of VTE, even in the absence of alcohol-related somatic complications. Our findings suggest that severe alcohol abuse increases the risk of VTE.

Cancer runs in families, suggesting a heritable component, but the contribution of environmental factors cannot be neglected. Studies on spousal risk can partly disentangle the environmental contribution but miss shared environmental factors during childhood and adolescence. Here, we examined the familial aggregation of common cancers among 80,281 Swedish-born adoptees, identified from the national Swedish Multigeneration Register, and linked them to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for common cancers (colorectal, lung, breast, prostate, and skin cancers) in the adoptees whose adoptive parents were diagnosed with concordant cancers, compared with the general population. SIRs in adoptees with an affected adoptive parent ranged from 1.00 (breast cancer) to 1.28 (skin cancer), whereas the SIRs in nonadoptees with an affected parent ranged from 1.63 (colorectal cancer) to 2.12 (skin cancer). Environmental factors account for around 0-28% of the familial aggregation. Cancer sites with high environmental contributions were observed for skin and colorectal cancers, which are known to have strong environmental causes.

Importance: Alcohol use disorder (AUD) runs strongly in families. It is unclear to what extent the cross-generational transmission of AUD results from genetic vs environmental factors., Objective: To determine to what extent genetic and environmental factors contribute to the risk for AUD., Design, Setting, and Participants: Follow-up in 8 public data registers of adoptees, their biological and adoptive relatives, and offspring and parents from stepfamilies and not-lived-with families in Sweden. In this cohort study, subtypes of AUD were assessed by latent class analysis. A total of 18,115 adoptees (born 1950-1993) and 171,989 and 107,696 offspring of not-lived-with parents and stepparents, respectively (born 1960-1993)., Main Outcomes and Measures: Alcohol use disorder recorded in medical, legal, or pharmacy registry records., Results: Alcohol use disorder in adoptees was significantly predicted by AUD in biological parents (odds ratio, 1.46; 95% CI, 1.29-1.66) and siblings (odds ratio, 1.94; 95% CI, 1.55-2.44) as well as adoptive parents (odds ratio, 1.40; 95% CI, 1.09-1.80). Genetic and environmental risk indices created from biological and adoptive relatives acted additively on adoptee AUD liability. Results from biological and adoptive relatives were replicated and extended from examinations of, respectively, not-lived-with parents and stepparents. Multivariate models in these families showed that AUD in offspring was significantly predicted by AUD, drug abuse, psychiatric illness, and crime in not-lived-with parents and by AUD, drug abuse, crime, and premature death in stepparents. Latent class analyses of adoptees and offspring of not-lived-with parents with AUDs revealed 3 AUD classes characterized by (1) female preponderance and high rates of psychiatric illness, (2) mild nonrecurrent symptoms, and (3) early-onset recurrence, drug abuse, and crime. These classes had distinct genetic signatures in the patterns of risk for various disorders in their not-lived-with parents and striking differences in the rates of recorded mood disorders., Conclusions and Relevance: Parent-offspring transmission of AUD results from both genetic and environmental factors. Genetic risk for AUD reflects both a specific liability to AUD and to other externalizing disorders. Environmental risk reflects features of both parental psychopathology and other aspects of the rearing environment. Alcohol use disorder is a heterogeneous syndrome and meaningful subtypes emerged from latent class analysis, which were validated by patterns of disorders in biological parents and specific psychiatric comorbidities. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.

Background: Varicose veins (VVs) have been associated with venous thromboembolism (VTE), but whether these diseases share familial susceptibility has not been determined. This nationwide study aimed to determine whether VTE shares familial susceptibility with VVs., Methods and Results: Swedish Multigeneration Register data for persons aged 0 to 76 years during the period 1964-2008 were linked to the Swedish Inpatient and Outpatient Registers. Familial risks (standardized incidence ratios [SIRs]) of VTE and VVs were examined in 2 ways (ie, bidirectionally): risk of VTE in subjects whose siblings had been diagnosed with VVs and risk of VVs in persons whose siblings had been diagnosed with VTE. The analyses were repeated for spouses to determine the importance of shared adult family environment. In total, 96 810 siblings had VVs and 87 564 had VTE. An increased risk of VTE was observed in persons whose siblings had VVs (SIR 1.30, 95% CI 1.26 to 1.33), whereas persons whose siblings had VTE had an increased risk of VVs (SIR 1.30, 95% CI 1.27 to 1.34). If 2 or more siblings were affected by VTE, the risk for VVs was 1.70 (95% CI 1.53 to 1.88). Conversely, if 2 or more siblings were affected by VVs, the risk for VTE was 1.52 (95% CI 1.38 to 1.67). In spouses of VTE patients, a minor increased risk of VVs was observed (SIR 1.05 for husbands, SIR 1.06 for wives). The risk of VTE in spouses of VV patients was similarly small (SIR 1.01 for husbands, SIR 1.05 for wives)., Conclusions: VVs and VTE share familial susceptibility. This novel finding suggests the existence of shared familial and possibly genetic factors., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Recent studies suggest de novo mutations may involve the pathogenesis of autism and attention-deficit/hyperactivity disorder (ADHD). Based on the evidence that excessive alcohol consumption may be associated with an increased rate of de novo mutations in germ cells (sperms or eggs), we examine here whether the risks of autism and ADHD are increased among individuals with a family history of alcohol use disorders (AUDs). The standardized incidence ratios (SIRs) of autism and ADHD among individuals with a biological parental history of AUDs were 1.39 (95% CI 1.34-1.44) and 2.19 (95% CI 2.15-2.23), respectively, compared to individuals without an affected parent. Among offspring whose parents were diagnosed with AUDs before their birth, the corresponding risks were 1.46 (95% CI 1.36-1.58) and 2.70 (95% CI 2.59-2.81), respectively. Our study calls for extra surveillance for children with a family history of AUDs, and further studies examining the underlying mechanisms are needed., (Copyright © 2014, Sundquist et al.)

Registry-based cancer incidence and mortality data are widely used for etiologic research, cancer control and health care monitoring and planning. The complete coverage of all cases is the key criteria of data quality but it is difficult to assess because the alternative sources of data may be flawed. The aim of our study was to examine, at a nationwide level, the completeness of the Swedish Cancer Registry (CR) regarding persons who died of cancer, based on the Cause of Death Registry (DR), and using the Hospital Discharge Registry (HDR) as an additional source of data. Individuals who died of cancer from years 1999 through 2008 recorded in DR were linked to CR and HDR. A total of 190,692 individuals were identified from DR with cancer as the underlying cause of death; the mean identification rate of concordant cancer in CR was 79.8%, depending on tumor site and age at death. Breast, bladder and prostate cancers showed the highest rate of identification, whereas bone, liver and pancreatic cancers showed the lowest rate of identification. CR had no records on 10.6% of cancer cases recorded in DR. Similarly, the identification rate in HDR was 84.5% for concordant cancer and with 9.6% of cases missing. Neither source reported cancers for 3.4% of cancer cases recorded in DR. In conclusion, some 10% of cancer deaths had no cancer records in CR or in HDR, and 3.4% were missing in both sources. The identification rate depended on tumor site, age at death and, to some extent, death outside hospital., (Copyright © 2012 UICC.)

The Swedish Family-Cancer Database comprises a total of 11.8 million individuals covering the Swedish population of the past 100 years. Version VIII of the Database is described in the present article. Cancer cases were retrieved from the Swedish Cancer Registry for the period 1958-2006, including more than 1 million first primary cancers. The number of familial cancers in offspring is 14,000 when a parent was diagnosed with a concordant (same) cancer and the number of concordant siblings was 6,000. From the year 1993 onwards histopathological data according to the SNOMED classification were used, which entails advantages for certain cancers, such as breast cancer. Even though the specific morphological classification only covers a limited number of years, it does cover most familial cancers in the offspring generation. The Database records the country of birth for each subject. A total of 1.79 million individuals were foreign born, Finns and other Scandinavians being the largest immigrant groups. The cancer incidence in the first-generation immigrants was compared to that in native Swedes using standardised incidence ratios (SIRs) to measure relative risk. The SIRs ranged widely between the immigrant groups, from 1.9-fold for myeloma to 25-fold for melanoma. The differences in SIRs were smaller in the second-generation immigrants. The usefulness and the possible applications of the Family-Cancer Database have increased with increasing numbers of cases, and the numerous applications have been described in some 300 publications. Familial cancer studies are in the stimulating interphase of the flourishing disciplines of genetics and epidemiology.

Although many studies have examined the associations between occupational exposures and kidney cancer, the evidence is not consistent. To examine the risk of occupational exposures on kidney cancer, we carried out a follow-up study on the economically active Swedish population, based on the latest update of the Swedish Family-Cancer Database. We calculated standardized incidence ratios (SIR) and 95% confidence intervals (CIs) for different occupational groups, adjusted for age, period, and socioeconomic status. The reference group was all the economically active population. An increased risk of renal parenchymal cancer was observed for miners and quarry workers, drivers, sales agents, transport workers, and public safety and protection workers among men, and launderers and dry cleaners among women. Significantly increased SIRs of renal pelvical cancer were also observed for the food manufacture workers among men, and journalists and shoe and leather industry workers among women. Male forestry workers, smelters, and metal foundry workers had increased risk for unspecified kidney cancer. Although smoking may explain some of these results, exposure to gasoline, diesel, their exposure products, some metal and chemicals in shoe and leather works, and dry-cleaning products may be associated with kidney cancer.