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Background: Aggregation of lung cancer (LCa) in family members is well-documented. However, little is known on the familial risk of LCa when first-degree relatives (FDRs, parents or siblings) are diagnosed with LCa as a second primary malignancy (LCa-2). We aimed to investigate whether and to what extent a family history of LCa-2 was associated with an increased LCa risk.Methods: In this Swedish national cohort we identified 127,865 individuals who had one FDR affected by LCa as a first primary cancer (LCa-1) and 15,490 individuals who had one FDR affected by LCa-2, respectively. We then estimated relative risk (RR) of LCa using those without cancer family history as reference.Results: The number of LCa-2 has been increasing annually and rather similarly in men and women in the last decade. Familial RR of LCa was 1.96 (95%, 1.85-2.07) for LCa-1 family history and 1.89 for LCa-2 (1.62-2.21). Risk was especially high when FDR was diagnosed with early-onset LCa-2 and when siblings were affected by LCa-2. The RR was 1.53 (1.10-2.12) when LCa-2 in FDR was diagnosed within 26 months after first primary cancer, and it increased to 2.16 (1.62-2.90) when LCa-2 was diagnosed between 74 to 154 months. Higher risk was observed for first primary cancer of the ovary (4.45, 1.85-10.7), nervous system (3.49, 1.45-8.38), upper aerodigestive tract (2.83, 1.78-4.49) and cervix (2.55, 1.41-4.61), and for non-Hodgkin lymphoma (3.13, 1.57-6.27).Conclusions: LCa risk is associated with diagnosis of LCa-2 in FDR to a similar degree as LCa-1 in FDRs. [ABSTRACT FROM AUTHOR]

The mortality in individuals with a family history of heart failure (HF) has not been determined. This nationwide sib-pair study aimed to determine mortality in individuals with a sibling affected with HF. Sib-pairs were linked using the Swedish Multi-Generation Register, the Hospital Discharge Register and the Cause of Death Register for the period 1987–2012. Families with cardiomyopathy or congenital heart disease were excluded. Mortality hazard ratios (HRs) were calculated for siblings of individuals who had been diagnosed with HF compared with siblings of individuals unaffected by HF as the reference group. Similar analyses were made for spouses. HRs were determined for overall mortality, cardiovascular mortality, and death of unknown cause. Among siblings, the adjusted HR for overall mortality was 1.21 (95% CI 1.18–1.25). This risk remained (HR = 1.19, 95% CI 1.15–1.23) also among subjects without HF themselves. The adjusted HRs for cardiovascular mortality and death of unknown cause were 1.39 (95% CI 1.32–1.45) and 1.58 (95% CI 1.29–1.95), respectively. The mortality risk associations with spousal HF were all minimal, with an overall mortality HR of 1.02 (1.01–1.02). Early sibling age of onset of HF < 50 years was associated with higher HRs for overall mortality, cardiovascular mortality, and death of unknown cause, 1.33 (1.27–1.41), 1.54 (1.40–1.68) and 1.84 (1.27–2.67), respectively. Sibling HF, especially early-onset HF, is associated with increased mortality. The low risk in spouses suggests genetic factors might be of importance. Screening for HF, and cardiovascular disease in general, in these individuals may be warranted. • Heart failure is a common, partly hereditary, condition with high mortality. • This study found an increased risk of death in relatives to heart failure patients. • The risk of death of unknown cause was especially high. • The results of this study can help identify individuals with a higher risk of death. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the association of socioeconomic status and comorbidities with uncomplicated and complicated diverticular disease (DD) in Sweden. Methods: We identified all individuals aged ≥30 years in Sweden diagnosed with DD between 1997 and 2012 using the Swedish National Population and Housing Census and the Hospital Discharge Register. Data were analyzed by multivariable logistic regression, with individual-level characteristics as covariates. Results: A total of 79,481 patients (median age 66 [range 30-86] years) were hospitalized for DD, 15,878 (20%) of whom for complicated DD. Admissions for both uncomplicated and complicated DD were more common in women ( p < 0.001). A low education level was identified as a risk factor for uncomplicated (unadjusted hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.75-1.82; adjusted HR 1.22, 95% CI 1.19-1.24) and complicated DD (unadjusted HR 1.84, 95% CI 1.77-1.92; adjusted HR 1.26, 95% CI 1.21-1.32). Patients with the lowest income had a lower risk of hospitalization for uncomplicated (adjusted HR 0.94, 95% CI 0.91-0.96) and complicated DD (adjusted HR 0.87, 95% CI 0.83-0.92) than those with the highest income. The correlation coefficient between income and education was 0.25. Diabetes and cardiovascular disease were identified as protective factors against uncomplicated DD (adjusted HR 0.68, 95% CI 0.66-0.69 and HR 0.79, 95% CI 0.74-0.84, respectively). Conclusions: Patients with the lowest education level had an increased risk of hospitalization for DD. Further studies are needed to explore the association of diabetes and cardiovascular disease with uncomplicated DD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Tonsillectomy is a common surgical procedure. Recent evidence suggests that tonsils play an important role in our immune system. We thus hypothesize that individuals with tonsillectomy may face an increased incidence of autoimmune diseases in their later life. Methods All individuals that had a tonsillectomy in Sweden between 1997 and 2012 were identified from the Swedish Hospital Discharge and Outpatient Register, and were followed until the diagnosis of a set of autoimmune diseases. Standardized incidence ratios (SIRs) were used to calculate the risk of autoimmune diseases as compared to the general population. Results A total of 179,875 individuals received a tonsillectomy in Sweden and 5357 of them were subsequently diagnosed with autoimmune diseases, giving an overall SIR of 1.34 (95%CI 1.30–1.37). For specific autoimmune diseases, 16 of them showed a significantly increased SIR, ranging between 1.21 and 2.97. The increased incidence was largely consistent irrespective of gender, age at operation, and underlying indications of tonsillectomy. Conclusions The incidence of a group of autoimmune diseases was higher in individuals operated with a tonsillectomy. Immune dysfunction due to tonsillectomy may partly explain the observed association. However, the underlying mechanisms need to be explored in future studies. [ABSTRACT FROM AUTHOR]

Background It is widely believed that autoimmune diseases affect predominantly in women, but the available evidence came from case control study with potential selection and recall bias. We aimed to examine the gender-specific incidence of autoimmune diseases by using national wide registers in Sweden. Methods Swedish Hospital Discharge Register and Outpatient Register were used to identify a set of autoimmune diseases between 1987 and 2010. Gender-specific incidence rate was standardized directly according to the Swedish age distribution in 2000. Results A total of 403,757 individuals were diagnosed with autoimmune diseases between 1987 and 2010 in Sweden. The overall incidence of 32 autoimmune disease was 60% higher in women than men. Female predominance was noted in 18 specific diseases, whereas the rest of them showed no difference or male predominance. The age of onset was different between men and women in 27 autoimmune diseases. Conclusions Our study suggested that the classical view of female predominance of autoimmune diseases may be far from striking than previously believed. Further studies are needed to examine whether there is true difference between men and women. [ABSTRACT FROM AUTHOR]

Abstract: Background: Little is known about whether the four main manifestations of arterial vascular disease (coronary heart disease=CHD, ischemic stroke, peripheral artery disease=PAD, and aortic (i.e. atherosclerosis/aneurysm) disease=AD) share familial susceptibility. The aim of this nationwide study was to determine the familial risks of concordant (same disease in proband and exposed relative) and discordant (different disease in proband and exposed relative) cardiovascular disease (CVD). Methods: Data from the Swedish Multigeneration Register on individuals aged 0–76years were linked to Swedish Hospital Discharge Register data for the period 1964–2008. Standardized incidence ratios (SIRs) for CHD (n =140,708 cases), ischemic stroke (n =73,771), PAD (n =18,982) and AD (n =7879) were calculated for siblings of individuals hospitalized due to CHD, stroke, PAD or AD compared to those of unaffected siblings. The procedure was repeated for parent–offspring and spouses. Results: All concordant and discordant sibling risks were increased for both males and females. Concordant risks were generally higher than discordant risks. The highest sibling risks were observed for premature concordant disease (<55years for males and <65years for females): SIR for CHD=1.93 (95% CI: 1.90–1.96), SIR for ischemic stroke=1.45 (1.39–1.50), SIR for PAD=2.76 (2.54–3.00), and SIR for AD=6.36 (5.28–7.59). Premature parent–offspring transmission followed the same pattern. The disease risk was modestly increased in spouses, highest for AD (SIR=1.48 (1.28–1.69)) and PAD (SIR=1.27 (1.21–1.32)). Conclusions: The four main manifestations of CVD share familial susceptibility, but unique site-specific familial factors may exist. [Copyright &y& Elsevier]

Abstract: Background: Stroke is common in cancer patients, but risk estimates for different cancer sites/types have not been determined. The aim of this nationwide study was to examine whether there is an association between cancer and first hospitalisation for haemorrhagic or ischaemic stroke. Methods: All 820,491 individuals in Sweden with a diagnosis of cancer between 1st January 1987 and 31st December 2008 were followed for first hospitalisation for haemorrhagic or ischaemic stroke. The reference population was the total population of Sweden without cancer. Standardised incidence ratios (SIRs) for haemorrhagic and ischaemic strokes were calculated. Results: Overall risk of haemorrhagic stroke and ischaemic stroke during the first 6months after diagnosis of cancer was 2.2 (95% confidence interval (CI)=2.0–2.3) and 1.6 (CI=1.5–1.6), respectively. For 18 and 20 of the 34 cancers studied, respectively, risk of haemorrhagic and ischaemic strokes was increased. Overall stroke risk decreased rapidly, but remained elevated, even 10+years after diagnosis of cancer 1.2 (CI=1.1–1.3) for haemorrhagic stroke and 1.1 (CI=1.1–1.2) for ischaemic stroke. The risk of stroke was highest during the first 6months after diagnosis of cancer of the nervous system (29 (CI=25–34) for haemorrhagic stroke and 4.1 (CI=3.4–4.8) for ischaemic stroke)) or leukaemia (13 (CI=10–16) for haemorrhagic stroke and 3.0 (CI=2.5–3.7) for ischaemic stroke)). Metastasis was associated with an increased risk of haemorrhagic stroke 2.2 (CI=1.8–2.7) and ischaemic stroke 1.5 (CI=1.3–1.7). Interpretation: Several cancer sites/types are associated with an increased risk of haemorrhagic and ischaemic strokes. [Copyright &y& Elsevier]

Summary: Background: Polyglutamine (polyQ) diseases are characterised by the expansion of CAG triplet repeats in specific genes. The accumulated encoded proteins affect the transcription of numerous transcription factors. We investigated whether polyQ diseases reduce the risk of cancer development. Methods: Data on patients with the polyQ diseases Huntington''s disease (HD), spinobulbar muscular atrophy (SBMA), and hereditary ataxia (HA) in Sweden were linked to the Swedish Cancer Registry. We calculated standardised incidence ratios for cancers at specific sites or of specific types and the risks were compared with those in the general population. We also analysed risks in the unaffected parents of patients. Findings: In the period January, 1969, to December, 2008, we identified 1510 patients with HD, 471 with SBMA, and 3425 with HA. Cancer was diagnosed in 91 (6·0%) HD patients, 34 (7·2%) SBMA patients, and 421 (12·3%) HA patients. The standardised incidence ratios were 0·47 (95% CI 0·38–0·58), 0·65 (0·45–0·91), and 0·77 (0·70–0·85), respectively. Before diagnosis of polyQ disease, the risk of cancer was even lower. Cancer incidence and risk in the unaffected parents of patients with polyQ diseases were similar to those in the general population. Interpretation: The consistently decreased incidence of cancer in patients with polyQ diseases suggests that a common mechanism protects against the development of cancer. This feature could be related to the polyQ-tract expansion seen in these diseases. Further studies are warranted to investigate the underlying mechanisms linking cancer and polyQ diseases. Funding: Swedish Cancer Society, Swedish Council for Working Life and Social Research. [Copyright &y& Elsevier]

BACKGROUND: Earlier studies have suggested that type 2 diabetes mellitus (T2DM) alters the risk of developing a variety of cancers, but little has been known about the impact of T2DM on cancer prognosis. On the basis of nationwide population-based Swedish registries, the authors of this report compared the cause-specific survival among cancer patients with and without T2DM. METHODS: Patients with T2DM were identified from the nationwide Swedish Hospital Discharge Register, and cancers were recorded from the Swedish Cancer Registry. Hazard ratios (HRs) were calculated using Cox regression models to compare variations in cause-specific survival between cancer patients with and without T2DM. RESULTS: Of the 1016,105 cancer patients, 16,123 had been hospitalized with T2DM before their diagnosis of cancer. The mortality rate was significantly higher among cancer patients with T2DM than among those without T2DM (cause-specific HR, 1.38; 95% confidence interval, 1.35-1.41). There were no differences in TNM stage distribution among cancer patients with or without T2DM for the main cancers, with an exception of tumor and metastatic classifications for breast cancer and prostate cancer, respectively. CONCLUSIONS: The current results indicated that patients with T2DM who are diagnosed with a subsequent cancer are at an increased risk for cause-specific mortality compared with patients who have cancer without T2DM. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Background: Risk of coronary heart disease (CHD) in cancer patients has not been thoroughly investigated. The aim of the present study was to examine whether there is an association between cancer and first hospitalisation for CHD. Methods: All individuals in Sweden with a diagnosis of cancer between 1st January 1987 and 31st December 2008 were followed for first hospitalisation for CHD. The reference population was the total population of Sweden without cancer. Standardised incidence ratios (SIRs) for CHD were calculated. Results: The overall CHD risk during the first 6months after diagnosis of cancer was 1.70 (95% confidence interval (95% CI) 1.66–1.75). For 26 of the 34 cancers studied, the risk of CHD was increased during the first 6months after diagnosis of cancer. The overall CHD risk decreased rapidly, but remained slightly elevated, even 10+years after diagnosis of cancer (SIR 1.07; 95% CI 1.04–1.11). The cancer sites/types for which risk of CHD was highest during the first 6months were small intestine (SIR 2.88; 95% CI 2.02–3.99), leukaemia (SIR 2.84; 95% CI 2.37–3.37), kidney (SIR 2.65; 95% CI 2.30–3.04), lung (SIR 2.56; 95% CI 2.35–2.80) and liver (SIR 2.28; 95% CI 1.91–2.71). Metastases were associated with an increased risk of CHD (SIR 1.46; 95% CI 1.28–1.65). Interpretation: Most cancers were associated with an increased risk of CHD during the first 6months after diagnosis. CHD risk was related to the presence of metastates. Cancer patients may need a more aggressive treatment of classical CHD risk factors. [Copyright &y& Elsevier]

Abstract: Background: Cancer and venous thromboembolism (VTE) are associated disorders. In the present nationwide study, we analyzed the risk of cancer in siblings, offspring and spouses of individuals hospitalized for VTE (and vice versa) with the aim of identifying shared familial risk factors for cancer and VTE. Material and Methods: The Multigeneration Register was linked to the Swedish Hospital Discharge Register and the Swedish Cancer Registry. Associations between the familial risks for VTE and cancer were examined by measuring the risk of developing specific cancers in the offspring of individuals diagnosed with VTE, and the risk of VTE in the offspring of individuals diagnosed with specific cancers. The analysis was repeated for siblings and spouses. Results: No overall associations between cancer and VTE were observed in parent-offspring pairs. In contrast, the risk of cancer was slightly increased in siblings of VTE patients (OR 1.03, 95% CI 1.01-1.06), and the risk of VTE was also increased in siblings of cancer patients (OR 1.07, 95% CI 1.04-1.10). Risks of cancer were also slightly increased in the husbands (OR 1.09, 95% CI 1.07-1.11) and wives (OR 1.02, 95% 1.00-1.05) of individuals with VTE. Conclusion: The present study provides evidence for minor familial risk factors shared by VTE and common cancers. These could be mostly environmental because of the positive associations in the spouse and sibling analyses and negative associations in the parent-offspring analysis, although the possibility of shared genetic risk factors also exists. [Copyright &y& Elsevier]

Objectives. Patients diagnosed with RA have an increased risk of some cancers. However, limited data are available on the important issue of prognosis of RA patients with cancer.Methods. RA patients were identified from the Swedish Hospital Discharge Register by linkage to the Cancer Registry. Follow-up of patients was started from the date of diagnosis of cancer through year 2006. Hazard ratios (HRs) were calculated in cancer patients with RA compared with subjects without RA.Results. A total of 1 411 163 cancer patients were identified in the database, of whom 6309 had a previous hospitalization for RA. Compared with all cancer patients without RA, patients with RA had a worse prognosis, with an HR of 1.29 and 1.31 for cause-specific and overall survival, respectively. For specific cancer sites, skin and breast cancers and non-Hodgkin's lymphoma showed worst survival. Age stratification did not change the results.Conclusion. Cancer patients with a previous hospitalization for RA had a worse prognosis for all and many site-specific cancers compared with patients without RA, independent of age at diagnosis and tumour staging. Improvement of survival for cancer patients with RA may require a multidisciplinary approach to accommodate the comorbidity. [ABSTRACT FROM PUBLISHER]

Background and aims. The incidence of celiac disease (CD) shows large, worldwide variation. However, whether its causes are environmental (gluten-containing diet) or genetic (specific haplotype) have not been established. The aim of the present study is to examine the incidence of CD among second-generation immigrants and adoptees from abroad to disentangle genetic/ethnic versus environmental influences (assuming that immigrants have similar gluten exposures to native Swedes, and thus differ from them only in terms of their genetic background). Methods. Second-generation immigrants and adoptees from abroad were identified in the MigMed 2 Database and were followed until diagnosis of CD, death, or the end of study. Standardized incidence ratios (SIRs) were calculated among these immigrants with native Swedes as the reference group. Results. A total of 1,050,569 children were defined as second-generation immigrants and the overall SIR of CD (SIR == 0.89, 95% confidence interval 0.84--0.94) was significantly lower than that of native Swedes. The incidence of CD among children with parents from Western, Eastern, and Northern European countries was similar to that in native Swedes, but was lower for those with parents from low-prevalence countries, especially Eastern and Southeast Asian countries. A total of 51,557 children born in foreign countries were adopted by Swedes. Adoptees from Eastern Asia had a significantly decreased SIR of CD. Conclusions. The decreased incidence of CD in second-generation immigrants and some groups of adoptees from abroad strongly suggests that ethnic genetic heterogeneity may contribute to the worldwide variation in CD incidence. [ABSTRACT FROM AUTHOR]

Background. Based on the evidence that vitamin D is involved in the development of immune system and vitamin D receptor gene is associated with asthma, we supposed that vitamin D is related to the development of asthma. Methods. Asthma patients were identified from the Swedish Hospital Discharge Register and the hospitalization rate was examined by different seasons and regions. Standardized incidence ratios (SIRs) for asthma were examined among patients hospitalized for osteoporosis compared with the general population. Results. A total of 172,384 patients were hospitalized for asthma in Sweden during 1965-2007. More patients were hospitalized in winter and North Sweden than in summer and South Sweden. The risk of asthma after osteoporosis was significantly increased, giving an overall SIR of 2.93. The risk was higher in male patients when compared with female subjects. Patients hospitalized for osteoporosis at age younger than 55 showed a high risk. Reversing the analyses and examining the risk of osteoporosis after hospitalization of asthma, SIR was significantly increased (3.54). Conclusion. Our study suggests that vitamin D, as indicated by the high risk of asthma after osteoporosis and the seasonal and regional variations of hospitalization, could play an important role for the development of asthma. [ABSTRACT FROM AUTHOR]

Introduction. Earlier studies suggest that histology has no prognostic significance in patients with invasive ovarian tumors. Studies about the effect of family history on survival have given conflicting results, which we try to clarify in this study. As an additional question, we examined whether family members share survival experience. Methods. We used the nation-wide Swedish Family-Cancer Database to estimate hazard ratios (HRs) for cause-specific and overall survival in ovarian cancer patients by histology and family history. HRs show the probability of death in the study group compared to the reference group. Results. A total of 6 049 ovarian cancer patients with specific histologies were retrieved from our Database from years 1993 to 1999. Compared to women with epithelial ovarian cancer, women with borderline epithelial tumors had the best survival (HR 0.02 and 0.14 for cause-specific and overall survival). Good survival was also noted for patients with sex cord-stromal tumors and germ cell tumors. Among specific subtypes of epithelial ovarian cancers, good survival was noted for women with clear cell and endometrioid carcinomas and mucinous cystadenocarcinoma. The study covered 80 mother-daughter pairs with a family history. Patients with a family history had a poorer survival than sporadic cases in both maternal and offspring generations. When the survival was analyzed according to the probands' length of survival, there was a non-significant concordance of prognosis. Conclusion. Our data showed that histology and family history are prognostic factors for ovarian tumors. Patients with a family history had a more aggressive course than the sporadic cases. [ABSTRACT FROM AUTHOR]

Reliable data on familial risks are important for clinical counseling and cancer genetics. However, population-based studies on familial soft tissue tumors are limited, which we will examine. Adjusted standardized incidence ratios (SIRs), calculated from the nation-wide Swedish Family Cancer Database, were used to measure the familial risk. There were 17 offspring-parent pairs with concordant soft tissue tumuors, the SIR was increased but not significant. Offspring soft tissue tumors were associated with paternal prostate and endocrine gland tumors and Hodgkin’s disease. Offspring myxosarcoma was associated with paternal endocrine gland tumors. Offspring fibrosarcoma was associated with parental stomach cancer and liposarcoma was associated with parental bladder cancer and maternal breast cancer. Leiomyosarcoma was associated with maternal breast cancer. The associations of myxosarcoma with melanoma and liposarcoma with non-Hodgkin’s lymphoma were noted among siblings. The present study showed that familial clustering of soft tissue tumors was limited to specific subtypes. Because of multiple comparisons, some of observed associations may be negative. Aggregation of melanoma and myxosarcoma among siblings may suggest Werner syndrome. A very small proportion of soft tissue sarcomas may be explained by Li–Fraumeni syndrome. Other novel associations, such as offspring liposarcoma with parental bladder cancer, and liposarcoma and non-Hodgkin’s lyhphoma among siblings, may be related to other unidentified familial diseases. [ABSTRACT FROM AUTHOR]

Abstract: We used the nation-wide Swedish Family-Cancer Database to examine the familial risks of histology-specific bone cancers in offspring by parental or sibling probands. Adjusted standardised incidence ratios (SIRs) were used to measure the risk. Among the 1327 offspring bone cancers, only two parent–offspring pairs and one sibling pair were noted with concordant bone cancer but the SIRs were not significant. Significant associations were observed in specific histological types or specific age groups, some of which may be chance findings arising from multiple comparisons. However, the risk of early-onset (<25 years) osteosarcoma in offspring was significantly increased when mothers presented with breast cancer (1.7) and melanoma (2.9), suggesting that Li–Fraumeni syndrome could partly explain this familial aggregation. Other associations, such as childhood osteosarcoma with parental liver cancer, Ewing’s sarcoma with kidney cancer and giant cell sarcoma with maternal breast cancer, were novel findings and may be related to other familial diseases. [Copyright &y& Elsevier]

Purpose: The aim of the study is to investigate associations between socioeconomic and occupational factors and lymphoproliferative (LP) diseases. Methods: We performed a follow-up study on the economically active Swedish population, based on the Swedish Family-Cancer Database. Standardized incidence ratios and 95% confidence intervals were calculated in different social classes and occupations. Results: An increased risk for LP diseases was observed for physicians, plumbers, chemical process workers, and food manufacture workers among men and shoe and leather workers, mechanics, iron and metalware workers, and launderers and dry cleaners among women. Conclusions: Results suggest that socioeconomic and occupational factors have a minor effect on risk for LP diseases. Exposure to organic solvents may increase the risk for some LP diseases, although inconsistencies of findings between subcohorts do not rule out spurious associations. [Copyright &y& Elsevier]

Background: The purpose of this study was to prospectively recruit patients treated with limb malformation and to explore the prevalence and the clinical and epidemiological features of Heart-Hand Syndrome (HHS) in China.Methods: The consecutive patients treated for congenital upper limb malformation in Beijing Ji Shui Tan Hospital from October 1st, 2016 to October 1st, 2019 were prospectively recruited. We reviewed the patients' medical records and identified patients with abnormal electrocardiogram (ECG) and/or abnormal ultrasonic cardiogram as well as their basic demographic and clinical characteristics.Results: A total 1653 (1053 male and 600 female) patients with congenital upper extremity malformations were prospectively recruited. Among them, 200 (12.1%) had abnormal ultrasonic cardiogram (181patients, 10.9%) and/or abnormal ECG (19 patients, 1.1%). The commonest type of abnormal heart structure was atrial septal defect (69/181 38.1%), and the commonest abnormal ECG was wave patterns (7/19, 36.8%). HHS patients had a higher comorbidity rate (11%) than non-HHS patients (6.9%). Patients with HHS were classified into four groups by the types of congenital upper extremity malformations, among which the most common group was thumb type (121/200, 60.5%).Conclusions: HHS occurred frequently among patients with congenital upper extremity malformation in China, particularly for those with multiple congenital malformations. The commonest type of hand malformations of HHS patients was thumb malformation. [ABSTRACT FROM AUTHOR]

Hepatitis D virus (HDV) is dependent on the presence of hepatitis B virus (HBV) for transmission and replication because of its inability to produce its own coat. It remains unclear whether HDV infection increases the risk of hepatocellular carcinoma. Using the Swedish Hospital Discharge Register and Outpatient Registry, we identified 9160 patients with chronic HBV infection between 1997 and 2008, of whom 327 had chronic HDV infection and 323 had acute HDV infection. Standardized incidence ratios (SIRs) were calculated for these patients compared with the general population. The risk of hepatocellular carcinoma was greatly increased in patients with HBV and HDV (SIR = 137.17, 95% confidence interval [CI] = 62.19 to 261.51). The risk of hepatocellular carcinoma among patients with HBV and HDV was increased (SIR = 6.11, 95% CI = 2.77 to 11.65) when patients with chronic HBV infection alone were used as the reference population. Similar results were observed for patients with chronic HDV infection (SIR = 99.26, 95% CI = 42.39 to 196.55). Our findings indicate that HDV is a strong risk factor for hepatocellular carcinoma. [ABSTRACT FROM PUBLISHER]

Purpose: Available evidence indicates that dipyridamole enhances the anti-thrombotic effects of aspirin for the prevention of secondary strokes. Aspirin is a well-known non-steroid anti-inflammatory drug. This anti-inflammatory property has turned aspirin into a potential drug for inflammation-related cancers such as colorectal cancer (CRC). Here, we aimed to explore whether the anti-cancer effect of aspirin against CRC could be improved by combined administration with dipyridamole. Methods: Population-based clinical data analysis was conducted to assess a possible therapeutic effect of combined dipyridamole and aspirin treatment in inhibiting CRC compared with either monotherapy. This therapeutic effect was further verified in different CRC mouse models, i.e. an orthotopic xenograft mouse model, an AOM/DSS mouse model, an Apcmin/+ mouse model and a patient derived xenograft (PDX) mouse model. The in vitro effects of the drugs on CRC cells were tested using CCK8 and flow cytometry assays. RNA-Seq, Western blotting, qRT-PCR and flow cytometry were used to identify the underlying molecular mechanisms. Results: We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone. The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect. Conclusions: Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further clinical studies confirm our findings, these may be repurposed as adjuvant agents. [ABSTRACT FROM AUTHOR]

Background: The familial risk of abdominal wall hernia (AWH) is largely unknown. In addition, it is unknown whether inguinal hernia (IH), femoral hernia (FH), incisional hernia (INH), epigastric hernia (EH), and umbilical hernia (UH) share familial susceptibility. The aim of this nationwide study was to determine the familial risks of concordant AWH (same disease in proband and exposed relative) and discordant AWH (different disease in proband and exposed relative). Study Design: Data from the Swedish Multigeneration Register on individuals aged 0 to 78 years were linked to the Swedish hospital discharge register and the Swedish outpatient register for the period from 1964 to 2010. Standardized incidence ratios (SIRs) and 95% CIs for surgically treated IH (n = 209,814 cases), FH (n = 4,576), INH (n = 19,494), EH (n = 8,257), and UH (n = 22,761) were calculated for siblings of individuals with hernia compared with the siblings of unaffected individuals. The procedure was repeated for spouses. Results: All concordant and most discordant familial sibling risks were increased. Familial concordant SIRs for siblings were IH = 1.97 (95% CI, 1.94–1.99), FH = 3.40 (95% CI, 2.44–4.62), INH = 2.24 (95% CI, 2.04–2.46), EH = 5.57 (95% CI, 4.64–6.64), and UH = 3.61 (95% CI, 3.33–3.91). Concordant familial risks were higher than discordant risks. For example, when the proband sibling had IH, the discordant SIRs were FH = 1.74 (95% CI, 1.61–1.88), INH = 1.22 (95% CI, 1.16–1.28), EH = 1.30 (95% CI, 1.20–1.40), and UH = 1.35 (95% CI, 1.29–1.41). Concordant SIRs for spouses were lower: IH = 1.23 (95% CI, 1.20–1.26), FH = 0.97 (95% CI, 0.64–1.36), INH = 1.56 (95% CI, 1.41–1.71), EH = 1.70 (95% CI, 1.09–2.45), and UH = 1.31 (95% CI, 1.09–1.56). Conclusions: Family history of surgically treated AWH is an important risk factor for surgical treatment of AWH. The 5 forms of AWH studied share familial susceptibility, but site-specific familial factors might exist. Several spouse risks were increased, suggesting the possibility of a nongenetic contribution to familial risks. [ABSTRACT FROM AUTHOR]

The evidence that dyslipidemia is associated with hyperglycemia calls for an investigation of whether dyslipidemia, as well as lipid-modifying agents, could affect the subsequent development of diabetic retinopathy (DR). Therefore, we aimed to address these unanswered questions by utilizing Mendelian randomization (MR) analysis. Genetic variants were selected from the UK Biobank as instruments to serve as proxies for lipid traits [high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (APOA-I) and apolipoprotein B (APOB)]. Univariable and multivariable MR analyses were performed to examine the associations of these lipid traits with DR and different levels of severity of DR. Based on the evidence for the effects of lipids on outcomes, we estimated the causal relevance of cholesteryl ester transfer protein (CETP) inhibitors in severe nonproliferative and proliferative DR using protein quantitative trait loci (pQTLs) and expression quantitative trait loci (eQTLs) as instruments. Genetically determined HDL-C levels were inversely associated with the risk of severe nonproliferative DR (OR = 0.70, 95% CI = 0.52–0.94) and proliferative DR (OR = 0.90, 95% CI = 0.83–0.97) in the main analyses utilizing the inverse variance-weighted (IVW) MR method and a couple of sensitivity analyses. No association was noted between genetically proxied CETP inhibitors and DR. This MR study suggests the casual protective roles of HDL-C in severe nonproliferative DR and proliferative DR, which calls for further studies to confirm these findings. Current lipid-modifying agents acting on HDL-C may not reduce the risk of DR and new treatments are required in the future. [Display omitted] • Mendelian randomization was used to assess the effects of lipids and drugs on diabetic retinopathy (DR). • HDL-C was inversely related to severe nonproliferative DR and proliferative DR. • No association between CETP inhibitor and DR was found. [ABSTRACT FROM AUTHOR]

Background Resilience has been shown to be protective against alcohol use disorders (AUDs), but the magnitude and nature of the relationship between these 2 phenotypes are not clear. The aim of this study was to examine the strength of this relationship and the degree to which it results from common genetic or common environmental influences. Methods Resilience was assessed on a 9-point scale during a personal interview in 1,653,721 Swedish men aged 17 to 25 years. AUD was identified based on Swedish medical, legal, and pharmacy registries. The magnitude of the relationship between resilience and AUD was examined using logistic regression. The extent to which the relationship arises from common genetic or common environmental factors was examined using a bivariate Cholesky decomposition model. Results The 5 single items that comprised the resilience assessment (social maturity, interest, psychological energy, home environment, and emotional control) all reduced risk for subsequent AUD, with social maturity showing the strongest effect. The linear effect by logistic regression showed that a 1-point increase on the resilience scale was associated with a 29% decrease in odds of AUD. The Cholesky decomposition model demonstrated that the resilience-AUD relationship was largely attributable to overlapping genetic and shared environmental factors (57 and 36%, respectively). Conclusions Resilience is strongly associated with a reduction in risk for AUD. This relationship appears to be the result of overlapping genetic and shared environmental influences that impact resilience and risk of AUD, rather than a directly causal relationship. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. We performed a nationwide cohort study to explore whether selective serotonin reuptake inhibitors (SSRIs) play a role in preventing CRC among individuals with family history. This report suggests that SSRI use was associated with a reduced incidence of CRC among people with a family history of CRC, and the decreased risk of CRC showed a non-linear, dose-dependent pattern. In addition, we found that the use of SSRIs was strongly associated with CRC diagnosed at an advanced stage rather than at an earlier stage, suggesting that the SSRIs might reduce the metastatic potential of cancer cells leading to stage migration. This population-based cohort study suggests that the use of SSRIs is associated with a reduced risk of CRC among individuals with a family history of CRC. Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. Preclinical and population-based evidence suggests that selective serotonin reuptake inhibitors (SSRIs) might play a role in preventing CRC. We performed a nationwide cohort study to explore whether the use of SSRIs could reduce CRC risk among individuals with family history. We identified individuals aged 50 and above who had one or more first-degree relatives diagnosed with CRC. A total of 38,617 incident SSRI users were identified and matched with 115,851 non-users, on a ratio of 1:3. The Cox regression model was used to calculate hazard ratios (HRs) and 95% CI confidence intervals (CIs). We found a significant negative association between SSRI use and the risk of CRC (adjusted HR, 0.77; 95% CI, 0.70–0.85). Restricted cubic spline regression showed a non-linear dose-responded relationship between SSRI use and CRC risk. The association was stronger in rectal cancer than colon cancer (adjusted HR, 0.73 vs. 0.79), and more pronounced in advanced-stage CRC than early-stage CRC (adjusted HR, 0.73 vs. 0.80). This population-based cohort study suggests that the use of SSRIs is associated with a reduced risk of CRC among individuals with a family history of CRC. [ABSTRACT FROM AUTHOR]

Background: Increasing number of individuals will have first-degree relatives (FDRs) diagnosed with colorectal cancer (CRC), as a second primary malignancy (CRCa-2) after a non-CRC cancer. We aimed to estimate whether and to what extent a family history of CRCa-2 is associated with an increased CRC risk.Methods: In this Swedish nationwide cohort study, rate ratio (RR) and cumulative incidence of CRC were estimated among 172,531 individuals with a family history of CRC as a first primary malignancy (CRCa-1) and 17,830 with a family history of CRCa-2, respectively, using individuals without cancer family history as the reference group.Results: A cumulative incidence of CRC by age 80 was 6.3 and 5.6% for individuals with a parental and a sibling family history of CRCa-2, respectively. RRs of CRC for one FDR diagnosed with CRCa-1 and CRCa-2 were respectively 1.72 (95% CI, 1.65-1.79) and 1.50 (1.32-1.70); the latter RR was lower than the former (P = 0.0356), but no difference was observed after adjusting age of diagnosis of CRC in FDR and family relationship (P = 0.6898). Increased RRs were found to be associated with a CRCa-2 diagnosis in FDR that occured after cancers in upper aerodigestive tract, breast, prostate, kidney and nervous system.Conclusions: Individuals who have relatives with CRCa-2 have an increased risk of CRC, but the magnitude is lower than those having relatives with CRCa-1, which is related to different ages of diagnosis of CRC in FDR and family relationships. [ABSTRACT FROM AUTHOR]

Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation. [ABSTRACT FROM AUTHOR]

PDE5 inhibitors was reported to play a protective role in both regulating lipid metabolism and reducing heart failure (HF). This study aimed to clarify the effectiveness of PDE5 inhibitors against hyperlipidemia-related HF by combining evidence from population-based study and animal models. The nationwide cohort study found that post-diagnostic use of PDE5 inhibitors was associated with a significantly lower risk of HF compared with patients who used alprostadil, especially among individuals with hyperlipidemia (adjusted HR = 0.56, 95% CI = 0.40–0.78). In animal models, sildenafil significantly recovered the cardiac structure and function induced by AAB surgery, as well as reversed liver dysfunction and ameliorated hyperlipidemia induced by HFD via reducing the level of ALT, AST and serum lipids. Lipidomic analysis identified four lipid metabolites involved in sildenafil administration, including FA 16:3, LPC O-18:1, DG24:0_18:0 and SE28:1/20:4. This study revealed the protective effect of PDE5 inhibitors against HF in hyperlipidemia, indicating the potential of being repurposed as an adjuvant for HF prevention in patients with hyperlipidemia if these findings can be further confirmed in clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: To investigate if the risk of prostate cancer (PC) differs based on the order of primary PC diagnosed in first‐degree relatives (FDRs) given possibly different risk factors for PC as first primary cancer (PCa‐1) and second primary cancer (PCa‐2). Subjects and Methods: In this Swedish nationwide cohort, PC diagnosis was followed for among 149,985 men with one FDR affected by PCa‐1, 10,972 with one FDR affected by PCa‐2 and 2,896,561 without any FDRs affected by cancer in a maximum of 57 years. PC patients were further followed for death due to PC since diagnosis. Relative risk (RR) of PC was estimated with Poisson regression and hazard ratio (HR) with Cox proportional hazard model. Results: Compared to men without any FDRs affected by cancer, the RRs of PC in men with one FDR affected by PCa‐1 and PCa‐2 were 2.12 (95% confidence interval [CI]: 2.07–2.17) and 1.69 (1.54–1.85), respectively. The risk in men with one FDR affected by PCa‐2 was significantly lower than those with one FDR affected by PCa‐1 after additionally adjusting for family relationship (father‐son and brothers) and age at diagnosis of PC in FDR (RR PCa‐2 vs PCa‐1, 0.85, 95% CI, 0.78–0.94). PC patients with a family history of PCa‐2 were more likely to be detected at late‐stage and less likely to be diagnosed by screening, compared to those with a family history of PCa‐1. Patients whose PC was diagnosed after the diagnosis of PCa‐1 in FDRs had a better survival than those without a family history of cancer (HR, 0.88, 95% CI, 0.80–0.97), but no such association was observed among patients with a family history of PCa‐2. Conclusion: Our study indicates a discrepancy between PC risks associated with a family history of PCa‐1 and PC‐2 and the reason behind it may be multifactorial. [ABSTRACT FROM AUTHOR]

Summary: The anti‐cancer potential of dipyridamole has been suggested from experiments, but evidence from population‐based studies is still lacking. We aimed to explore if dipyridamole use was related to a lower risk of lymphoid neoplasms. We identified individuals with prescription of aspirin after diagnosis of ischaemic cerebrovascular disease since 2006 by linking several Swedish registers. In these aspirin users, those with dipyridamole prescription were further identified as the study group and patients without dipyridamole were randomly selected as reference group with 1:1 ratio using a propensity score‐matching approach. After a median of 6·67 years of follow‐up, a total of 46 patients with dipyridamole use developed lymphoid neoplasms with an incidence rate of 0·49 per 1 000 person‐years, while the rate in the matched group was 0·74 per 1 000 person‐years. As compared to non‐users, dipyridamole users were associated with a significantly decreased risk of lymphoid neoplasms [hazard ratio (HR) = 0·65; 95% confidence interval (CI) = 0·43‐0·98]. Specifically, the reduced risk was observed for non‐Hodgkin lymphomas (HR = 0·64; 95% CI = 0·42‐0·94), especially B‐cell lymphomas (HR = 0·56; 95% CI = 0·35‐0·88). Dipyridamole use was related to a lower risk of lymphoid neoplasms, indicating a clinical potential of dipyridamole to be an adjunct anti‐tumour agent against lymphoid neoplasms. [ABSTRACT FROM AUTHOR]

Background: With the increasing number of breast cancer (BC) diagnosed as a second primary malignancy after a first primary non-breast cancer (BCa-2), it is unclear about the familial risk of BC among women with a first-degree relative (FDR, parents or siblings) affected by a BCa-2.Methods: In this Swedish nationwide cohort study, 5315 women with a FDR affected by BCa-2 and 115,048 women with a FDR affected by BC as the first primary cancer (BCa-1) were followed for the first primary invasive BC diagnosis. Relative risk (RR) of BC was estimated through Poisson regression by using 2,743,777 women without a family history of cancer as reference. The risk was stratified by the diagnostic age of BC in FDR, proband type, the time interval between the first primary cancer and BCa-2 in FDR as well as the site of first primary cancer diagnosed in FDR before BCa-2. We also calculated the cumulative incidence of BC from birth to a specific age for the three groups.Results: The cumulative incidence from birth to age 70 was 10% among women with a family history of BCa-2. The RR of BC with a family history of BCa-2 (RR, 1.68, 95%CI, 1.49 to 1.88) was comparable to that with BCa-1 (1.68, 1.63 to 1.73). The risk was largely consistent irrespective of proband type. The age of onset of BCa-2 in FDR (RR early-onset, 1.72 vs. RR late-onset 1.67) had less influence on the risk compared to BCa-1 in FDR (1.89 vs. 1.63). In the analysis stratified by the time between the first primary cancer and BCa-2 in relatives, the risks were largely similar. For the site of first primary cancer diagnosed in FDR before BCa-2, the increased BC risk was found in women whose FDRs were diagnosed with first primary gastric, colorectal, endometrial, ovarian, nervous system and endocrine gland cancers, and non-Hodgkin lymphoma.Conclusions: Women with a family history of BCa-2 have a similar overall BC risk as those with a family history of BCa-1. The risk varied according to the site of first primary cancer diagnosed in FDR before BCa-2. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Patients with autoimmune (AI) diseases are diagnosed with increased frequencies of some cancers, which may depend on the underlying dysregulation of the immune system or treatment. Data on female cancers are limited. Methods: We analyzed systematically risk and survival of female cancers of the breast, uterus, ovary and other genital organs in close to 200,000 patients diagnosed with any of 33 different AI diseases. Standardized incidence ratios (SIRs) for risk and hazard ratios (HRs) for survival were calculated for subsequent incident cancers or cancer deaths up to year 2008. Results: For all breast cancer after any AI diseases, the SIR was 0.94; SIRs were modestly increased after two AI diseases and decreased after nine AI diseases, including Sjogren syndrome (0.46). For cervical cancer, the risk was increased after discoid lupus erythematosus (3.34) and systemic sclerosis (2.43). The HR was 2.12 in chronic rheumatic heart disease patients. The overall SIR for endometrial cancer was 0.85, with low SIR in ankylosing spondylitis (0.37); the HR was 4.05 for Sjogren syndrome. The SIR for ovarian cancer was increased for polymyositis/dermatomyositis (3.26) while the HR was increased for multiple sclerosis (2.43). The overall SIR for other genital cancers was increased to 1.54 and a very high risk of 35.88 was observed in localized scleroderma. Conclusions: Breast, endometrial and ovarian cancers were decreased after all AI diseases and most significant changes after individual AI diseases were towards lower risks. Probably treatment related factors explain the findings. For cervical and other genital cancers all significant changes were increased risks. [Copyright &y& Elsevier]

To evaluate compliance to workflow and accuracy of tests in Sweden's first fast-track referral pathway for patients with nonspecific symptoms and suspected cancer (SCAN). Prospective cohort study with consecutive inclusion of patients referred to the diagnostic center (DC). Patients with nonspecific symptoms were examined in primary care according to a protocol including two test packages and diagnostic imaging. If symptoms were not explained, patients were referred to the DC and a DC-test package was taken. At the DC, further investigations resulted in diagnosis/no diagnosis. A total of 290 patients, median age 69 years (interquartile range [IQR] 59–76), 48% men, participated. A total of 64 (22%) were diagnosed with cancer, 186 (64%) with non-malignant disease and 40 (14%) had no new disease. Compliance was estimated by percentage of compulsory tests taken. Test accuracy was assessed by likelihood ratios (LRs) regarding cancer. A total of 23 (8%) patients had taken both primary care packages, whereas 150 (52%) patients went through entire diagnostic imaging. Abnormal pulmonary X-ray, peak expiratory flow (PEF) and calcium had the highest LRs in primary care (3.5; 3.2; 2.7). A total of 105 (36%) took the complete DC-package, of which bilirubin and cytomegalovirus had the highest LRs (11.5; 10.9). The median number (IQR) of abnormal primary care tests was 5 (3–6) for cancer, 3 (2–6) for other diagnoses and 1 (0–3) for no diagnosis. Compliance to test packages in primary care was low, which warrants review of the workflow. Few single tests had high accuracy regarding cancer, but the number of abnormal tests can provide guidance in complicated investigations of suspected malignancies. Fast-track referral pathways for patients with nonspecific serious symptoms have been implemented in several countries and are part of the national cancer strategy in all of Scandinavia. Compliance with compulsory tests in primary care was modest in this study; 8% of the patients had taken the entire compulsory test packages. Few single compulsory tests had high accuracy regarding subsequent cancer, which warrants a review of tests and examinations. However, patients diagnosed with cancer had a higher number of abnormal test results compared to the other groups. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and is known for its high resistance and low response to treatment. Tumor immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Karyopherin alpha 2 (KPNA2), a member of the nuclear transporter family, is elevated in multiple human cancers and accelerates carcinogenesis. However, the specific role of KPNA2 in PDAC remains unclear. In this study, we found that expression of KPNA2 was significantly upregulated in PDAC compared to adjacent nontumor tissue and its high expression was correlated with poor survival outcome by analyzing the GEO datasets. Similar KPNA2 expression pattern was also found in both human patient samples and KPC mouse models through IHC staining. Although KPNA2 knockdown failed to impair the vitality and migration ability of PDAC cells in vitro, the in vivo tumor growth was significantly impeded and the expression of immune checkpoint ligand PD-L1 was reduced by silencing KPNA2. Furthermore, we uncovered that KPNA2 modulated the expression of PD-L1 by mediating nuclear translocation of STAT3. Collectively, our data suggested that KPNA2 has the potential to serve as a promising biomarker for diagnosis in PDAC. [ABSTRACT FROM AUTHOR]

Background: Expensive cancer treatment calls for alternative ways such as drug repurposing to develop effective drugs. The aim of this study was to analyse the effect of post-diagnostic use of cholera vaccine on survival outcome in breast cancer patients.Methods: Cancer diagnosis and cholera vaccination were obtained by linkage of several Swedish national registries. One vaccinated patient was matched with maximum two unvaccinated individuals based on demographic, clinical and socioeconomic factors. We performed proportional Cox regression model to analyse the differences in overall and disease-specific survivals between the matched patients.Results: In total, 617 patients received cholera vaccine after breast cancer diagnosis. The median (interquartile range) time from diagnosis to vaccination was 30 (15-51) months and from vaccination to the end of follow-up it was 62 (47-85) months. Among them, 603 patients were matched with 1194 unvaccinated patients. Vaccinated patients showed favourable overall survival (hazard ratio (HR): 0.54, 95% confidence interval (CI): 0.37-0.79) and disease-specific survival (HR: 0.53, 95% CI: 0.33-0.84), compared to their unvaccinated counterpart. The results were still significant in multiple sensitivity analyses.Conclusions: Post-diagnostic use of cholera vaccine is associated with a favourable survival rate in breast cancer patients; this provides evidence for repurposing it against breast cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Fast-track referral is an increasingly used method for diagnostic evaluation of patients suspected of having cancer. This approach is challenging and not used as often for patients with only nonspecific symptoms. In order to expedite the diagnostics for these patients, we established Sweden's first Diagnostic Center (DC) focusing on outcomes related to diagnoses and diagnostic time intervals. Material and Methods: The study was designed as a prospective cohort study. Patients aged ≥18 years who presented in primary care with nonspecific symptoms of a serious disease were eligible for referral to the DC after having completed an initial investigation. Acceptable diagnostic time intervals were defined to be a maximum of 15 days in primary care and 22 days at the DC. Diagnostic outcome, length of diagnostic time intervals and patient satisfaction were evaluated. Results: A total of 290 patients were included in the study. Cancer was diagnosed in 22.1%, other diseases in 64.1%, and no diagnosis was identified in 13.8% of these patients. Patients diagnosed with cancer were older, had shorter patient interval (time from first symptom to help-seeking), shorter DC-interval (time from referral decision in primary care to diagnosis) and showed a greater number of symptoms compared to patients with no diagnosis. The median primary care interval was 21 days and the median DC interval was 11 days. Few symptoms, no diagnosis, female sex, longer patient interval, and incomplete investigations were associated with prolonged diagnostic time intervals. Patient satisfaction was high; 86% of patients reported a positive degree of satisfaction with the diagnostic procedures. Conclusions: We demonstrated that the DC concept is feasible with a diagnosis reached in 86.2% of the patients in addition to favorable diagnostic time intervals at the DC and a high degree of patient satisfaction. [ABSTRACT FROM AUTHOR]

Increased risks of certain cancers have been observed in patients with hepatitis C virus ( HCV) infection. However, data on other cancer sites/types are lacking. We analyzed systematically the risk of developing 35 common cancers in patients with HCV infection using a nationwide Swedish database. Patients with HCV infection were identified from the Swedish Hospital Inpatient and Outpatient Register and Primary Health Care Database, and followed until the diagnosis of cancer. Standardized incidence ratios ( SIRs) were calculated for subsequent 35 common cancer sites/types between 1990 and 2010 in patients with HCV infection in Sweden. Increased risks were recorded for six cancers. The highest SIR was seen for liver cancer (36.67; 95% CI: 33.20-40.40). The decreased risk was for prostate cancer (0.73; 95% CI: 0.59-0.90) and melanoma (0.50; 95% CI: 0.30-0.79). A significant sex-difference for cancer was observed only for liver cancer (40.72; 95% CI: 36.36-45.45 for men and 27.21; 95% CI: 21.90-33.41 for women). Also, increased SIRs were noted only for liver cancer during the entire period of follow-up. HCV infection was associated with an increased incidence of liver cancer and additionally five other types of cancer. Active surveillance of other cancers may be needed in order to be diagnosed at an earlier stage. [ABSTRACT FROM AUTHOR]

Background: Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. Preclinical studies suggest that the anti-malaria drug proguanil and atovaquone might play a role in preventing CRC, but population-based evidence is still lacking.Methods: By accessing a couple of nationwide Swedish registers, we performed a cohort study to explore whether using proguanil and atovaquone might associate with a lower risk of CRC by adopting a new-user study design. Adults who have 1 or more first-degree relatives (parents or siblings) diagnosed with CRC were identified and linked with the Prescribed Drug Register to evaluate their administration history of proguanil and atovaquone. Survival analysis of the time to CRC diagnosis with Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: A total of 16,817 incident proguanil/atovaquone users were identified and matched with 168,170 comparisons, who did not use proguanil/atovaquone, on the ratio of 1:10. We found a significant negative association between proguanil/atovaquone use and risk of CRC (adjusted HR, 0.76; 95% CI, 0.62-0.93). Test for trend showed significant dose- and duration-response correlations (P < 0.001). The association was more pronounced in CRC diagnosed at an advanced stage than at an early stage (adjusted HR, 0.69 vs.0.81).Conclusions: This national-wide population-based cohort study showed that the use of proguanil and atovaquone was associated with a reduced risk of CRC among individuals with a family history of CRC. [ABSTRACT FROM AUTHOR]

Background Medical adherence is important in the treatment of depression. Primary medical adherence, i.e. patients collecting their newly prescribed medications from pharmacies, is very different depending on the drug prescribed Objective To assess the rate of primary medical adherence in patients prescribed antidepressants and to identify characteristics that make patients less likely to pick up prescriptions. Methods An observational study was performed using primary health care data from Sweden on patients who were prescribed antidepressants. Univariate and multivariate logistic regression was used to determine differences in pick-up rate according to patient characteristics. Main outcome Pick-up rate, defined as collection of a prescription within 30 days. Results A total of 11 624 patients received an antidepressant prescription during the study period, and the overall pick-up rate was 85.1%. The pick-up rate differed according to country of birth: individuals born in the Middle East and other countries outside Europe had lower primary medical adherence than Swedes, with adjusted odds ratios (ORs) of 0.58 and 0.67, respectively. Patients at ages 64-79 years had a higher pick-up rate compared with those aged 25-44 years (OR 1.71). Divorced patients had a lower rate compared with married patients (OR 0.80). Conclusion Immigrants from the Middle East and other countries outside Europe and younger and divorced patients had lower primary medical adherence, which calls for clinical attention and preventive measures. [ABSTRACT FROM AUTHOR]

Background.Previous studies found an increased risk of cancer in hospitalized asthma patients, but it is not known whether patients from primary health care show a similar risk pattern. In addition, it is unclear whether the diagnosis of asthma can influence the prognosis of subsequent cancer. Methods.Asthma patients were identified from Swedish inpatient, outpatient, and primary health care registers, and were linked to the Swedish Cancer Registry to identify subsequent diagnoses of cancer. Standardized incidence ratios (SIRs) were used to examine the risk of cancer in asthma patients compared with subjects without asthma. In addition, we used Cox proportional hazards regression to estimate hazard ratios (HRs) for mortality in patients with both asthma and cancer. Results.A total of 10 649 cancers were diagnosed in patients with previous asthma, with a SIR of 1.19 (95% CI 1.17–1.21). A total of 15 cancer sites showed an increased incidence, whereas two cancer sites showed a decreased risk. Non-allergic asthma showed the highest risk of cancer (SIR = 1.25, 95% CI 1.18–1.32), followed by unspecified asthma (SIR = 1.22, 95% CI 1.19–1.25), status asthmaticus (SIR = 1.19, 95% CI 1.02–1.39), and allergic asthma (SIR = 1.14, 95% CI 1.06–1.22). The risk of cancer was similarly increased in asthma patients diagnosed in primary health care and those diagnosed in hospitals. Cancer patients with previous asthma had increased mortality, with a HR of 1.55 (95% CI 1.50–1.60). HRs ranged from 1.09 to 1.94 for different sites/types of cancer. Conclusions.Patients with asthma, irrespective of whether they were treated in primary health care or hospitals, had an increased risk of cancer. In addition, cancer patients with previous asthma had a worse prognosis compared with those without asthma, suggesting that these patients may require a multidisciplinary approach to manage the comorbidity. [ABSTRACT FROM AUTHOR]

Background We aimed at assessing familial risk of melanoma by considering a detailed family history of multiple primary (invasive/in situ) melanomas (MPM), stratified by histology and location. Methods Among 65,429 melanoma patients diagnosed in 1958–2010 in the Swedish Family-Cancer Database, there were 4248 patients with familial melanoma. A detailed family history of MPM was investigated by number of melanomas in one first-degree relative (FDR) and in ⩾2 FDRs. Familial melanoma risk was assessed by standardised incidence ratios (SIRs) comparing those with family history of melanoma to those without. Combining invasive/in situ melanoma was due to essentially identical familial risks. Results For one affected FDR, familial risk increased from SIR = 2.2 (95% confidence interval (CI) = 2.2–2.3) for single melanoma to 16.3 (9.5–26.1) for ⩾5 melanomas, while for ⩾2 affected FDRs, the risk increased from 5.5 (4.8–6.2) for single melanoma to 23.9 (13.6–38.8) for ⩾2 melanomas. Significantly higher familial risks for superficial spreading melanoma (SSM) [2.5 (2.3–2.6)] than lentigo maligna melanoma (LMM) [1.8 (1.6–2.1)], and for multiple parts [5.3 (3.1–8.4)] and trunk [2.6 (2.5–2.8)] than head/neck [2.0 (1.8–2.2)] were observed. Only at head/neck, significantly higher risk for SSM [2.4 (1.9–3.0)] than LMM [1.6 (1.4–1.8)] was noted. Conclusion We found, for the first time, that familial risks were similar for two/three melanomas in one FDR or for a single melanoma in ⩾2 FDRs and, higher familial risks for SSM than LMM occurred only at head/neck. This study provides new evidence for genetic counselling in melanoma, suggesting the need for considering not only the number of affected family members but also the diagnosis of MPM (even in situ) in relatives. [ABSTRACT FROM AUTHOR]