Background- This nationwide study sought to determine age- and gender-specific familial risks in siblings hospitalized for venous thromboembolism (VTE). Methods and Results- The Swedish Multigeneration Register on 0- to 75-year-old subjects was linked to the Hospital Discharge Register for the years 1987-2007. Standardized incidence ratios were calculated for individuals whose siblings were hospitalized for VTE compared with those whose siblings were not affected. Among a total of 45 362 hospitalized cases with VTE, 2393 affected siblings were identified, with a familial standardized incidence ratio of 2.45 (95% confidence interval [CI], 1.66 to 3.61). Gender-specific differences in incidence rates were observed. The familial risks were significantly increased from the age of 10 to 69 years, with a familial standardized incidence ratio of 4.77 (95% CI, 1.96 to 10.83) at ages 10 to 19 years, which decreased to 2.08 (95% CI, 1.35 to 3.20) at ages 60 to 69 years, although the absolute risk increased with age. The familial standardized incidence ratios for siblings with 2 and =3 affected probands were 51.87 (95% CI, 31.47 to 85.00) and 53.69 (95% CI, 25.59 to 108.50), respectively. Spouses had low familial risks (standardized incidence ratio=1.07; 95% CI, 1.04 to 1.10; observed spouse cases=3900). Conclusions- Familial factors, although influenced by age and gender, are important risk factors for VTE. The present study shows that VTE is aggregated in families and suggests that uncovering the sources of familial aggregation (genetic and nongenetic) may be worthwhile. Moreover, in a small fraction of siblings, the familial risk was very high, suggesting segregation of rare but strong genetic risk factors.
Dr. Bengt Zöller, Center for Primary Health Care Research, CRC, Building 28, Floor 11, Jan Waldenströms gata 35, Skåne University Hospital, S-205 02 Malmö, Sweden, Tel.: +46 70 6691476, Fax: +46 40 391370, E-mail: firstname.lastname@example.org
Seasonal variation in venous thromboembolism (VTE) risk in individuals with familial predisposition to VTE has not been explored. This nationwide study aimed to determine whether there are age- and sex-specific seasonal differences in risk of hospitalisation of VTE among individuals with and without a family history of VTE. The Swedish Multi-Generation Register was linked to Hospital Discharge Register data for the period 1964-2010. Seasonal variation in first VTE events in 1987-2010 for individuals with and without a family history of VTE (siblings or parents) was determined by several independent methods. Stratified analyses were performed according to age, sex, and VTE subtype (pulmonary embolism [PE] or deep venous thrombosis [DVT]). Seasonal variation in VTE incidence, mostly with a peak during the winter, was observed in both sexes in individuals with and without family history with overall peak-to-low ratios (PLRs) of 1.15 and 1.21, respectively. The peak day was December 25 and February 1 for those with and without a family history of VTE, respectively. Seasonal variation was strongest among individuals aged >50 years. Among individuals aged 0-25 years with a family history, the peak for VTE was in July (PLR = 1.20). Significant seasonal variation was observed for PE and DVT with the exception of DVT among those with a family history (PLR = 1.01). In conclusion, our data support the presence of a modest seasonal variation of VTE among individuals with and without a family history of VTE. However, young age and family history may modify and attenuate the effect of season on VTE.
BACKGROUND: Systematic comparisons of mode of inheritance for renal cell carcinoma (RCC) have not been carried out. The occurrence of cancer in parents and offspring may be due to dominant causes, whereas cancer affecting only siblings may indicate a recessive causation. Environmental effects need to be excluded. METHODS: The Swedish Family-Cancer Database includes all Swedes born after 1931 with their biologic parents, totaling 10.2 million persons. Cancer data were retrieved from the Swedish Cancer Registry from years 1961 to 2000, included 2415 cases of RCC in offspring and 18531 in parents. Standardized incidence ratios (SIRs) and 95% CI limits were calculated for offspring whose parents or sibling were diagnosed with RCC. RESULTS: The SIRs for siblings for RCC depended on their age difference. SIR was 7.63 (95% CI 3.63-14.08) when the age difference was less than 3 years and compared to 3.43 (95% CI 1.77-6.02) for large age difference. SIRs for familial risk of RCC were 1.73 (95% CI 1.31-2.26) when a parent and 4.58 (95% CI 2.87-6.94) when a sibling had RCC. Age-specific analysis of familial RCC among siblings revealed maxima at ages 40 to 49 and 60 to 68 years. CONCLUSION: The findings in the present study offer evidence on recessive effects in early onset RCC.
To study the association between country of birth and incident atrial fibrillation (AF) in several immigrant groups in Sweden. The study population included all adults (n = 3,226,752) aged 45 years and older in Sweden. AF was defined as having at least one registered diagnosis of AF in the National Patient Register. The incidence of AF in different immigrant groups, using Swedish-born as referents, was assessed by Cox regression, expressed in hazard ratios (HRs) and 95% confidence intervals (CI). All models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighbourhood socioeconomic status. Compared to their Swedish-born counterparts, higher incidence of AF [HR (95% CI)] was observed among men from Bosnia 1.74 (1.56-1.94) and Latvia 1.29 (1.09-1.54), and among women from Iraq 1.96 (1.67-2.31), Bosnia 1.88 (1.61-1.94), Finland 1.14 (1.11-1.17), Estonia 1.14 (1.05-1.24) and Germany 1.08 (1.03-1.14). Lower incidence of AF was noted among men (HRs = 0.60) from Iceland, Southern Europe (especially Greece, Italy and Spain), Latin America (especially Chile), Africa, Asia (including Iraq, Turkey, Lebanon and Iran), and among women from Nordic countries (except Finland), Southern Europe, Western Europe (except Germany), Africa, North America, Latin America, Iran, Lebanon and other Asian countries (except Turkey and Iraq). In conclusion, we observed substantial differences in incidence of AF between immigrant groups and the Swedish-born population. A greater awareness of the increased risk of AF development in some immigrant groups may enable for a timely diagnosis, treatment and prevention of its debilitating complications, such as stroke.
The incidences of both type 1 diabetes (T1D) and T2D are increasing worldwide. T2D is associated with many cancers. However, no data are available on cancer of unknown primary (CUP), a relatively common, fatal cancer for which tobacco smoking is the only known risk factor. At diagnosis, CUP metastases are found in various organs, which has implications for prognosis. We carried out a nationwide study on the association of CUP with T1D and T2D. 32?600 T1D patients and 178?000 T2D patients were identified from the national healthcare registers and these were linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for CUP from 1997 through 2010 using anyone without diabetes as a reference. The SIR of CUP in 421 diabetic patients was 1.71, highest for CUP with liver (2.17) and respiratory system (1.95) metastases. The SIR was 2.91 for T1D, but with a small number of patients, 1.38 for T2D with insulin treatment, and 1.78 for the main group of T2D. CUP with liver and respiratory system metastases increased for each diabetic type; however, for T2D, CUP with gastrointestinal and bone metastases also increased. The results provide the first demonstration that CUP is one of the cancers associated with diabetes, with definite evidence on T2D. CUP has a poor prognosis, which may be even worse when diabetes is the underlying comorbidity. A mechanistic question for future work is to determine whether diabetes promotes primaries that escape detection or their metastatic spread.
We used the nationwide Swedish Family-Cancer Database to analyse cancer risks in 613,000 adult immigrants to Sweden. All the immigrants had become parents in Sweden and their median age at immigration was 24 years for men and 22 years for women. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 18 cancer sites using native Swedes as a reference. Data were also available from compatriot marriages. All cancer was decreased by 5% and 8% for immigrant men and women, respectively. However, most of the male increase was due to lung cancer for which male immigrants showed a 41% excess. Among individual cancer sites and immigrant countries, 110 comparisons were significant, 62 showing protection and 48 an increased risk. Most of the differences between the rates in immigrants and Swedes could be ascribed to the variation of cancer incidence in the indigenous populations. Some high immigrant SIRs were 5.05 (n = 6, 95% CI 1.82-11.06) for stomach cancer in Rumanian women and 2.41 (41, 1.73-3.27) for lung cancer in Dutch men. At some sites, such as testis, prostate, skin (melanoma), kidney, cervix and nervous system, the SIRs for immigrants were decreased; in some groups of immigrants SIRs were about 0.20. The highest rates for testicular cancer were noted for Danes and Chileans. Women from Yugoslavia and Turkey had an excess of thyroid tumours. All immigrant groups showed breast, endometrial and ovarian cancers at or below the Swedish level but the differences were no more than 2-fold.
We used the nationwide Swedish Family-Cancer Database to analyze cancer risks in Sweden-born descendants of immigrants from European and North American countries. Our study included close to 600,000 0-66-year-old descendants of an immigrant father or mother. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 17 cancer sites using native Swedes as a reference. All cancer was marginally below the Swedish incidence in offspring of immigrant origin. Decreased SIRs were observed for breast cancer among Norwegian descendants, melanoma among descendants of Hungarian fathers and ovarian and bladder cancer among descendents of Finnish mothers, all consistent with the difference in cancer incidence between Swedes and the indigenous populations. Cervical cancer was increased in daughters of Danish men, whereas thyroid cancer and non-Hodgkin's lymphoma were in excess in offspring of parents of Yugoslav and Asian descent. Even these results agreed with the high incidence rates in parents compared to Swedes, except that for non-Hodgkin's lymphoma other explanations are needed; these may be related to immune malfunction. Comparison of the results between the first- and the second-generation immigrants suggest that the first 2 decades of life are important in setting the pattern for cancer development in subsequent life. Birth in Sweden sets the Swedish pattern for cancer incidence, irrespective of the nationality of descent, while entering Sweden in the 20s is already too late to influence the environmentally imprinted program for the cancer destiny.
Twin studies on cancer have addressed two general questions, one about the possible carcinogenic effects of twinning and the second about heritable effects of cancer. The first question is answered by comparing the occurrence of cancer in twins to that in singletons; the second is answered in probandwise analysis of monozygotic twins compared to dizygotic twins or siblings. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 62,574 0-66-year-old twins to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all main cancer compared to cancer in singletons. In probandwise analysis, the SIR was calculated for the co-twin of an affected twin. The overall risk of cancer in same or opposite sex twins was at the level of the risk for singletons. Testicular cancer was increased among same sex twins and all twins to an SIR of 1.43. Melanoma was decreased in these groups of twins to an SIR of 0.84. Some other cancer sites were increased or decreased in some groups of twins, but none in all twins. The SIR of breast cancer was 1.01 and 1.04 in same and opposite sex twins, respectively. Probandwise analysis showed increased risks for Hodgkin's disease in males and breast cancer and childhood acute lymphoid leukemia among females. The data on this unselected population of twins suggest that twinning per se is not a risk factor of cancer. However, because twins are smaller than singletons at birth, some possible effects could be masked by such differences. In utero hormonal exposures may be related to the risk of testicular cancer. The protective effects in melanoma may be due to socioeconomic factors.
The prevalence of obesity, as well as use of bariatric surgery, has increased worldwide. The aim of the present study was to investigate the potential differences in the use of bariatric surgery among Swedes and immigrants in Sweden and whether the hypothesized differences remain after adjustment for socioeconomic factors.
A closed cohort of all individuals aged 20-64 years was followed during 2001-2010. Further analyses were performed in 2 periods separately (2001-2005 and 2006-2010). Age-standardized cumulative incidence rates (CR) of bariatric surgery were compared between Swedes and immigrants considering individual variables. Cox proportional hazards models were used in univariate and multivariate models for males and females.
A total of 12,791 Swedes and 2060 immigrants underwent bariatric surgery. The lowest rates of bariatric surgery were found in immigrant men. The largest difference in CR between Swedes and immigrants was observed among low-income individuals (3.4 and 2.3 per 1000 individuals, respectively). Adjusted hazard ratios (HRs) were lower for all immigrants compared with Swedes in the second period. The highest HRs were observed among immigrants from Chile and Lebanon and the lowest among immigrants from Bosnia. Except for Nordic countries, immigrants from all other European countries had a lower HR compared with Swedes.
Men in general and some immigrant groups had a lower HR of bariatric surgery. Moreover, the difference between Swedes and immigrants was more pronounced in individuals with low socioeconomic status (income). It is unclear if underlying barriers to receive bariatric surgery are due to patients' preferences/lack of knowledge or healthcare structures. Future studies are needed to examine potential causes behind these differences.
Cites: J Gen Intern Med. 2007 Jul;22(7):908-1417447097
To investigate an association between autoimmune disorders (AID) and hospitalization for dementia and Alzheimer's disease, and to study whether the risk is associated with follow-up time and age.
We followed up all individuals in Sweden without previous hospital admission for dementia and Alzheimer's disease, and with a primary or secondary diagnosis of an AID between 1 January 1964 and 31 December 2010, in the Swedish National Patient Register for dementia and Alzheimer's disease. The Swedish National Patient Register includes both inpatients and outpatients. We calculated standardized incidence ratios (SIR) for dementia and Alzheimer's disease, adjusted for individual variables, including age, sex and comorbidities.
A total of 788 103 individuals were admitted to hospital because of an autoimmune disorder without previous dementia and Alzheimer's disease. Among a total of 42 conditions of AID, 9998 dementia and Alzheimer's disease patients were identified with a SIR of 1.28 (95% CI 1.26-1.31). A total of 17 showed an increased risk, and of those the remaining, 14 conditions were still at risk, when dementia and Alzheimer's disease diagnosed in the year of AID diagnosed were excluded. The risks depended on the age at hospitalization for dementia and Alzheimer's disease.
The present large study quantified the increased risks of dementia and Alzheimer's disease in patients with many types of AID. Geriatr Gerontol Int 2018; 18: 1350-1355.