Smokers’ increased risk for disability pension: social confounding or health-mediated effects? Gender-specific analyses of the Hordaland Health Study cohort

78 Background: Increased integration of tumor biomarker data into prostate cancer epidemiology studies is needed to identify molecular subtypes that underlie its etiology and progression. We hypothesize that the TMPRSS2:ERG gene fusion is a unique prostate cancer subtype that is etiologically distinct from cancers lacking TMPRSS2:ERG. Methods: We leveraged the Physicians’ Health Study and Health Professionals Follow-up Study cohort data on pre- and post-diagnostic lifestyle factors, inherited genetic variants, circulating biomarkers, and clinical data and follow-up for 30 years. We have a tumor repository of men with prostate cancer and tumor tissue microarrays. Using immunohistochemistry, we characterized TMPRSS2:ERG status for 1,491 incident prostate cancer cases in these cohorts, and also have biomarker data on a range of additional markers from immunohistochemistry and mRNA expression profiling. Results: Fifty percent of prostate cancer cases were ERG-positive. ERG-positive cancers show much higher expression of insulin/IGF signaling, PTEN loss, higher VDR expression, as well as expression of mismatch repair genes. In contrast, ERG-negative prostate cancer is characterized by increased presence of chronic inflammation and atrophy. We found higher pre-diagnostic free testosterone levels, but not other sex hormones, were associated with increased risk of ERG-positive (OR = 1.4, 95% CI = 1.0-1.8) but not ERG-negative disease (OR = 0.9, 95% CI = 0.7-1.2). Of 39 known genetic risk loci, six were significantly associated (p < 0.05) with ERG+ versus ERG- cancer (2 expected by chance). Prostate cancer risk factors such as taller height (an indicator of growth factors in puberty) are uniquely associated with ERG-positive prostate cancer. Moreover, we observe a complex interaction of components of insulin/IGF and ERG-status on prostate cancer mortality. Conclusions: TMPRSS2:ERG is a highly prevalent somatic event in prostate cancer that likely defines a unique molecular subtype of this common disease. Understanding the differences between these two prostate cancer subtypes may enhance opportunities for prevention.

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Physical health-related quality of life predicts disability pension due to musculoskeletal disorders: seven years follow-up of the Hordaland Health Study Cohort

BMC Public Health ◽

10.1186/1471-2458-14-167 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 7

Author(s):

Inger Haukenes ◽

Erlend H Farbu ◽

Trond Riise ◽

Grethe S Tell

Keyword(s):

Quality Of Life ◽

Musculoskeletal Disorders ◽

Disability Pension ◽

Health Study ◽

Study Cohort ◽

Health Related Quality ◽

Related Quality ◽

Health Related

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Prediagnostic plasma adiponectin and survival among patients with colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.526 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 526-526

Author(s):

Dawn Q. Chong ◽

Raaj Mehta ◽

Mingyang Song ◽

Dmitriy Kedrin ◽

Jeffrey A. Meyerhardt ◽

...

Keyword(s):

Colorectal Cancer ◽

Statistical Tests ◽

Cox Proportional Hazards Model ◽

Health Study ◽

Enzyme Linked Immunosorbent Assay ◽

Study Cohort ◽

Plasma Adiponectin ◽

Increased Risk ◽

Overall Mortality

526 Background: Adiponectin is a hormone secreted by adipose tissue and has been demonstrated to possess anticarcinogenic, anti-inflammatory and insulin-sensitizing effects. Circulating adiponectin has been shown to be inversely associated with the risk of colorectal cancer (CRC) in prospective studies. However, the association of prediagnostic adiponectin with survival among patients with established colorectal cancer is unclear. Methods: We conducted a prospective study of 621 incident colorectal cancer cases from the Nurses’ Health Study and Health Professionals Follow-up Study to evaluate the association between prediagnostic plasma adiponectin and mortality. Plasma adiponectin levels were determined by enzyme-linked immunosorbent assay from ALPCO Diagnostics. The interbatch coefficient of variation from quality control samples randomly interspersed among the case samples was 8.6%. We examined the associations between quartiles of plasma adiponectin and mortality using a Cox proportional hazards model adjusted for established and putative risk factors. All statistical tests were two sided. Results: After a median follow-up of 9 years, there were 267 (43%) total deaths and 130 (21%) CRC deaths in the total study cohort. Compared with patients in the lowest quartile of adiponectin, patients in the highest quartile had a multivariate hazard ratio (HR) for CRC-specific mortality of 2.70 [95% confidence interval (CI), 1.54-4.75; Ptrend = 0.001]. The corresponding multivariate HR for overall mortality was 1.64 (95% CI, 1.14-2.36; Ptrend = 0.007). These associations were reasonably consistent in analyses according to subgroups defined by age, gender, body mass index, stage, grade and site of primary cancer. Similar results were yielded after excluding patients diagnosed within 4 years of blood collection (Ptrend = 0.027). Conclusions: Prediagnostic adiponectin is associated with an increased risk of colorectal cancer- specific and overall mortality. Further studies are needed to elucidate the mechanistic basis for these findings and determine the potential role of adiponectin as a prognostic marker in colorectal cancer.

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Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort study

Annals of the Rheumatic Diseases ◽

10.1136/ard.2007.080937 ◽

2008 ◽

Vol 68 (4) ◽

pp. 514-518 ◽

Cited By ~ 33

Author(s):

L A Mandl ◽

K H Costenbader ◽

J F Simard ◽

E W Karlson

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Maternal Diabetes ◽

Health Study ◽

Age At Menarche ◽

Study Cohort ◽

Fetal Origins ◽

Adult Disease ◽

Increased Risk ◽

Post Menopausal

Objectives:The “fetal origins of adult disease” hypothesis suggests the uterine environment can influence the susceptibility of a fetus to future disease. We examine whether the fetal environment, as reflected by birthweight, could modulate an individual’s future risk of rheumatoid arthritis (RA).Methods:The relationship between birthweight and the risk of incident RA was studied in 87 077 women followed prospectively in the Nurses’ Health Study cohort. New cases of RA diagnosed between 1976 and 2002 were confirmed in 619 women. The association between birthweight and the future development of RA was studied in age-adjusted and Cox proportional hazard models adjusting for age and potential confounders, including history of maternal diabetes, childhood socioeconomic status, prematurity, maternal and paternal smoking, as well as additionally adjusting for risk factors for RA including smoking, age at menarche, use of oral contraceptives, use of post-menopausal hormones, total lifetime breastfeeding, and body mass index (BMI) at age 18.Results:In an age-adjusted model, birthweight >4.54 kg vs birthweight 3.2–3.85 kg was associated with a two-fold increased risk of RA (relative risk (RR) = 2.1, 95% CI 1.4 to 3.3). Further adjusting for potential confounders and risk factors did not change this relationship (RR = 2.0, 95% CI 1.3 to 3.0). Findings were similar when we limited cases to those with rheumatoid factor positive RA (RR = 2.1, 95% CI = 1.2 to 3.6).Conclusions:In this large prospective cohort, birthweight >4.54 kg was associated with a two-fold increased risk of adult onset RA, compared with those of average birthweight. Further study of this observation may provide insight into the pathogenesis of RA.

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Different diagnostic groups and labour market marginalization among refugee youths

European Journal of Public Health ◽

10.1093/eurpub/ckaa165.1313 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

J Chen ◽

E Mittendorfer-Rutz ◽

P Klimek

Keyword(s):

Disability Pension ◽

Public Health Importance ◽

Refugee Youth ◽

Relative Risks ◽

Increased Risk ◽

The Mean ◽

External Causes ◽

Hypertensive Diseases ◽

Risk Ratios ◽

Risk For Disability

Abstract Background Refugees are at increased risk of labor market marginalization (LMM), which is of high Public Health importance. However, little is known whether specific multimorbidity patterns increase the risk of LMM in this group. We sought to examine whether different diagnostic groups associate with subsequent unemployment and disability pension in refugee youth as compared to their counterparts born in Sweden. Methodology We analyzed 249,245 individuals between the age of 16 and 26 at 31.12.2011 from a combined Swedish registry. Refugees were matched to five second-generation-native-born Swedes. LMM was defined as disability pension or > 180 days of unemployment, 2012-2015. Relative risks (RR) were calculated for 114 diagnostic groups (2009-11) with regard to the two outcome measures. Results The mean age was 23±1.7 years, 2,841 (1.1%) received disability pension and 16,323 (6.5%) individuals experienced unemployment. The majority of diagnostic groups was associated with a higher risk for unemployment and a lower risk for disability pension in refugees. Hypertensive diseases and external causes of morbidity showed higher risk ratios of unemployment for refugees compared to Swedish-born: RRs (95% Confidence Interval) 6.8 (3.16, 14.6) and 6.31 (4.45, 8.94), respectively. Diabetes and mental disorders were associated with higher risk estimates for disability pension in refugees: RRs (95% CI) 2.4 (1.02, 5.6) and 1.8 (0.80, 3.9), respectively. Conclusions Diagnoses are differentially associated with LMM in refugee youth as compared to Swedish-born individuals. In order to prevent LMM in refugees, early intervention for the identified diseases is important. Key message The importance of diagnostic groups for subsequent LMM differs for young refugees and Swedish-born individuals. Findings are also divergent regarding the measure of LMM.

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Disability pension by occupational class - the impact of work-related factors: The Hordaland Health Study Cohort

BMC Public Health ◽

10.1186/1471-2458-11-406 ◽

2011 ◽

Vol 11 (1) ◽

Cited By ~ 50

Author(s):

Inger Haukenes ◽

Arnstein Mykletun ◽

Ann Kristin Knudsen ◽

Hans-Tore Hansen ◽

John Gunnar Mæland

Keyword(s):

Disability Pension ◽

Health Study ◽

Study Cohort ◽

Occupational Class ◽

Related Factors ◽

Work Related ◽

The Impact

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Secondhand nicotine vaping at home and respiratory symptoms in young adults

Thorax ◽

10.1136/thoraxjnl-2021-217041 ◽

2022 ◽

pp. thoraxjnl-2021-217041

Author(s):

Talat Islam ◽

Jessica Braymiller ◽

Sandrah P Eckel ◽

Feifei Liu ◽

Alayna P Tackett ◽

...

Keyword(s):

Young Adults ◽

Respiratory Symptoms ◽

Parental Education ◽

Respiratory Health ◽

Health Study ◽

Study Cohort ◽

Shortness Of Breath ◽

Mixed Effect ◽

Increased Risk ◽

Study Participants

RationaleDespite high prevalence of e-cigarette use (vaping), little is currently known regarding the health effects of secondhand nicotine vape exposure.ObjectiveTo investigate whether exposure to secondhand nicotine vape exposure is associated with adverse respiratory health symptoms among young adults.MethodWe investigated the effect of secondhand nicotine vape exposure on annually reported wheeze, bronchitic symptoms and shortness of breath in the prospective Southern California Children Health Study cohort. Data were collected from study participants (n=2097) with repeated annual surveys from 2014 (average age: 17.3 years) to 2019 (average age: 21.9). We used mixed effect logistic regression to evaluate the association between secondhand nicotine vape and respiratory symptoms after controlling for relevant confounders.ResultsPrevalence of secondhand nicotine vape increased from 11.7% to 15.6% during the study period in this population. Prevalence of wheeze, bronchitic symptoms and shortness of breath ranged from 12.3% to 14.9%, 19.4% to 26.0% and 16.5% to 18.1%, respectively, during the study period. Associations of secondhand nicotine vape exposure with bronchitic symptoms (OR 1.40, 95% CI 1.06 to 1.84) and shortness of breath (OR 1.53, 95% CI 1.06 to 2.21) were observed after controlling for vaping, active and passive exposure to tobacco or cannabis, and demographic characteristics (age, gender, race/ethnicity and parental education). Stronger associations were observed when analysis was restricted to participants who were neither smokers nor vapers. There were no associations with wheezing after adjustment for confounders.ConclusionSecondhand nicotine vape exposure was associated with increased risk of bronchitic symptoms and shortness of breath among young adults.

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Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-219483 ◽

2021 ◽

Vol 80 (5) ◽

pp. 598-604

Author(s):

Cindy G Boer ◽

Ingrid Szilagyi ◽

N Long Nguyen ◽

Tuhina Neogi ◽

Ingrid Meulenbelt ◽

...

Keyword(s):

Vitamin K ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Matrix Gla Protein ◽

Study Cohort ◽

Single Nucleotide Variants ◽

Increased Risk ◽

Coagulation Proteins ◽

Clinical Prevention

ObjectivesVitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP.MethodsWe investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of MGP and VKORC1 single nucleotide variants on this association.ResultsAcenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94–3.20), both for knee (OR=2.34, 95% CI=1.67–3.22) and hip OA (OR=2.74, 95% CI=1.82–4.11). Among acenocoumarol users, carriers of the high VKORC1(BB) expression haplotype together with the MGP OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69–6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78–1.33).ConclusionsThese findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.

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Exploring the Epidemiology of Cancer after Solid Organ Transplantation (EpCOT): an observational cohort study

BMJ Open ◽

10.1136/bmjopen-2020-043731 ◽

2021 ◽

Vol 11 (4) ◽

pp. e043731

Author(s):

Adnan Sharif ◽

Javeria Peracha ◽

David Winter ◽

Raoul Reulen ◽

Mike Hawkins

Keyword(s):

Organ Transplantation ◽

Record Linkage ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Study Cohort ◽

Solid Organ ◽

Post Transplantation ◽

Increased Risk ◽

Risk Of Cancer

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.

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