Inherited Thrombophilias Are Associated with an Increased Risk of COVID-19 Associated Venous Thromboembolism: A Prospective Population-Based Cohort Study

Abstract Background: COVID-19 is associated with high rates of venous thromboembolism (VTE). The impact of common inherited thrombophilias on the development of COVID-19-associated VTE (COVID-19 VTE) is not well understood. Objective: To determine if the presence of inherited thrombophilias modifies the risk of COVID-19 VTE or COVID-19 mortality. Methods: Prospective population-based cohort study evaluating adult participants of the UK Biobank diagnosed with COVID-19 between November 2019 and May 2021. Individuals were of European descent and aged between 45 and 69 at recruitment to UK Biobank. We evaluated six single nucleotide polymorphisms including rs6025 (Factor V Leiden mutation) and rs1799963 (Prothrombin mutation) in addition to two polygenic risk scores (PRS-VTE and PRS-ABO). A genome-wide association study was performed for associations with COVID-19 VTE. COVID-19 VTE was defined using International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for VTE following COVID-19 diagnosis. COVID-19 mortality was defined using ICD-10 codes for COVID-19 on the death certificate. Results: Demographic and clinical characteristics are shown in Table 1. Of the 13 712 COVID-19 positive individuals included in the analysis, the median age was 54 years and 52.5% were female. There were 197 (1.4%) cases of COVID-19 VTE and 890 (6.5%) died due to COVID-19. The rs6025 variant, synonymous with FVL, was associated with a 1.8-fold risk of COVID-19 VTE (95% CI 1.040-2.931) (Table 2). The risk of COVID-VTE was also increased with rs2066865 (OR 1.345; 95% CI 1.074-1.675) and the PRS-VTE (OR 1.262; 95% CI 1.081-1.468) (Table 2). COVID-19 VTE was associated with increased COVID-19 mortality (OR 2.731; 95% CI 1.885-3.901) but this study found no association between the studied inherited thrombophilias and COVID-19 mortality (Table 2). On genome-wide analysis, two novel SNPs, rs4975019 and rs2875853, located on chromosomes 4 and 16 respectively, were associated with an increased occurrence of COVID-19 VTE. Conclusions: These data demonstrate that several inherited thrombophilias increase the risk of COVID-19 VTE and suggest that two novel SNPs are associated with COVID-19 VTE. These results suggest that certain inherited thrombophilias may assist in characterising a subgroup of COVID-19 patients at higher risk of thrombotic events who require individualised antithrombotic therapy. Future prospective studies are required to evaluate inherited thrombophilias in this patient cohort. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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The risk of venous thromboembolism after surgery for esophagogastric malignancy and the impact of chemotherapy: a population-based cohort study

Diseases of the Esophagus ◽

10.1093/dote/doz079 ◽

2019 ◽

Vol 33 (6) ◽

Author(s):

Alfred Adiamah ◽

Lu Ban ◽

Joe West ◽

David J Humes

Keyword(s):

Gastric Cancer ◽

Cohort Study ◽

Venous Thromboembolism ◽

Adjuvant Chemotherapy ◽

Cumulative Incidence ◽

Population Based ◽

Risk Of Death ◽

Increased Risk ◽

Esophagogastric Cancer ◽

The Impact

SUMMARY To define the incidence of postoperative venous thromboembolism (VTE) and effects of chemotherapy in a population undergoing surgery for esophagogastric cancer. This population-based cohort study used linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data from England to identify subjects undergoing esophageal or gastric cancer surgery between 1997 and 2014. Exposures included age, comorbidity, smoking, body mass index, and chemotherapy. Crude rates and adjusted hazard ratios (HRs) were calculated for rate of first postoperative VTE using Cox regression models. The cumulative incidence of VTE at 1 and 6 months was estimated accounting for the competing risk of death from any cause. Of the 2,452 patients identified, 1,012 underwent gastrectomy (41.3%) and 1,440 esophagectomy (58.7%). Risk of VTE was highest in the first month, with absolute VTE rates of 114 per 1,000 person-years (95% CI 59.32–219.10) following gastrectomy and 172.73 per 1,000 person-years (95% CI 111.44–267.74) following esophagectomy. Neoadjuvant and adjuvant chemotherapy was associated with a six-fold increased risk of VTE following gastrectomy, HR 6.19 (95% CI 2.49–15.38). Cumulative incidence estimates of VTE at 6 months following gastrectomy in patients receiving no chemotherapy was 1.90% and esophagectomy 2.21%. However, in those receiving both neoadjuvant and adjuvant chemotherapy, cumulative incidence following gastrectomy was 10.47% and esophagectomy, 3.9%. VTE rates are especially high in the first month following surgery for esophageal and gastric cancer. The cumulative incidence of VTE at 6 months is highest in patients treated with chemotherapy. In this category of patients, targeted VTE prophylaxis may prove beneficial during chemotherapy treatment.

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Body mass index and risk of all-cause mortality in normotensive and hypertensive adults: The Rural Chinese Cohort Study

Public Health Nutrition ◽

10.1017/s1368980021001592 ◽

2021 ◽

pp. 1-25

Author(s):

Qionggui Zhou ◽

Xuejiao Liu ◽

Yang Zhao ◽

Pei Qin ◽

Yongcheng Ren ◽

...

Keyword(s):

Cohort Study ◽

Population Based ◽

Normal Weight ◽

Sensitivity Analyses ◽

Hypertension Status ◽

Moderation Effect ◽

Increased Risk ◽

All Cause Mortality ◽

Chinese Cohort ◽

The Impact

Abstract Objective: The impact of baseline hypertension status on the BMI–mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI–mortality association using a rural Chinese cohort. Design: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. Setting: Longitudinal population-based cohort Participants: 17,262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. Results: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the HRs (95% CI) for mortality in normotensive participants were 1.92 (1.23-3.00), 1.44 (1.01-2.05), 1.14 (0.82-1.58), 0.96 (0.70-1.31), 0.96 (0.65-1.43), 1.32 (0.81-2.14), and 1.32 (0.74-2.35) respectively, and in hypertensive participants were 1.85 (1.08-3.17), 1.67 (1.17-2.39), 1.29 (0.95-1.75), 1.20 (0.91-1.58), 1.10 (0.83-1.46), 1.10 (0.80-1.52), and 0.61 (0.40-0.94) respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity versus normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. Conclusions: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

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Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-021-02494-4 ◽

2021 ◽

Author(s):

Shuai Yuan ◽

Maria Bruzelius ◽

Susanna C. Larsson

Keyword(s):

Renal Function ◽

Venous Thromboembolism ◽

Mendelian Randomization ◽

Causal Effect ◽

Meta Analysis ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Genome Wide ◽

Increased Risk ◽

Mr Study

AbstractWhether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10−8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.

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Renin–angiotensin system blocker use and the risk of acute kidney injury after colorectal cancer surgery: a population-based cohort study

BMJ Open ◽

10.1136/bmjopen-2019-032964 ◽

2019 ◽

Vol 9 (11) ◽

pp. e032964

Author(s):

Charlotte Slagelse ◽

H Gammelager ◽

Lene Hjerrild Iversen ◽

Kathleen D Liu ◽

Henrik T Toft Sørensen ◽

...

Keyword(s):

Colorectal Cancer ◽

Acute Kidney Injury ◽

Cohort Study ◽

Angiotensin Receptor Blockers ◽

Kidney Injury ◽

Population Based ◽

Adjusted Risk ◽

Increased Risk ◽

The Impact ◽

Postoperative Aki

ObjectivesIt is unknown whether preoperative use of ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) affects the risk of acute kidney injury (AKI) after colorectal cancer (CRC) surgery. We assessed the impact of preoperative ACE-I/ARB use on risk of AKI after CRC surgery.DesignObservational cohort study. Patients were divided into three exposure groups—current, former and non-users—through reimbursed prescriptions within 365 days before the surgery. AKI within 7 days after surgery was defined according to the current Kidney Disease Improving Global Outcome consensus criteria.SettingPopulation-based Danish medical databases.ParticipantsA total of 9932 patients undergoing incident CRC surgery during 2005–2014 in northern Denmark were included through the Danish Colorectal Cancer Group Database.Outcome measureWe computed cumulative incidence proportions (risk) of AKI with 95% CIs for current, former and non-users of ACE-I/ARB, including death as a competing risk. We compared current and former users with non-users by computing adjusted risk ratios (aRRs) using log-binomial regression adjusted for demographics, comorbidities and CRC-related characteristics. We stratified the analyses of ACE-I/ARB users to address any difference in impact within relevant subgroups.ResultsTwenty-one per cent were ACE-I/ARB current users, 6.4% former users and 72.3% non-users. The 7-day postoperative AKI risk for current, former and non-users was 26.4% (95% CI 24.6% to 28.3%), 25.2% (21.9% to 28.6%) and 17.8% (17.0% to 18.7%), respectively. The aRRs of AKI were 1.20 (1.09 to 1.32) and 1.16 (1.01 to 1.34) for current and former users, compared with non-users. The relative risk of AKI in current compared with non-users was consistent in all subgroups, except for higher aRR in patients with a history of hypertension.ConclusionsBeing a current or former user of ACE-I/ARBs is associated with an increased risk of postoperative AKI compared with non-users. Although it may not be a drug effect, users of ACE-I/ARBs should be considered a risk group for postoperative AKI.

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Endogenous sex hormone levels in men are not associated with risk of venous thromboembolism: the Tromsø study

Acta Endocrinologica ◽

10.1530/eje-08-0888 ◽

2009 ◽

Vol 160 (5) ◽

pp. 833-838 ◽

Cited By ~ 19

Author(s):

Johan Svartberg ◽

Sigrid K Brækkan ◽

Gail A Laughlin ◽

John-Bjarne Hansen

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Free Testosterone ◽

Population Based ◽

Sex Hormone ◽

Population Based Study ◽

Hormone Levels ◽

Increased Risk ◽

The Impact

ObjectivesLow testosterone levels in men have been associated with cardiovascular risk factors and atherosclerosis and lately also an increased risk of both cardiovascular disease (CVD) and all-cause mortality. As arterial CVDs and venous thromboembolism (VTE) have been shown to share common risk factors, the purpose of the present study was to determine the impact of endogenous sex hormone levels on the incidence of VTE in a cohort of men.DesignA prospective, population-based study.MethodsSex hormone measurements were available in 1350 men, aged 50–84, participating in the Tromsø study in 1994–1995. First, lifetime VTE-events during the follow-up were registered up to September 1 2007.ResultsThere were 63 incident VTE-events (4.5 per 1000 person-years) during a mean of 10.4 years of follow-up. Age was significantly associated with increased risk of VTE; men 70 years or older had a 2.5-fold higher risk of VTE (HR 2.47, 95% CI 1.19–5.12), compared with those between 50 and 60 years of age. In age-adjusted analyses, endogenous sex hormones levels were not associated with risk of VTE; for each s.d. increase, hazards ratios (95% CI) were 1.06 (0.83–1.35) for total testosterone, 1.02 (0.79–1.33) for free testosterone, and 1.27 (0.94–1.71) for ln-estradiol. In dichotomized analyses comparing men in the lowest total and free testosterone quartile with men in the higher quartiles, hypoandrogenemia was not associated with risk of VTE.ConclusionsIn this population-based study of middle-aged and older men, endogenous sex hormone levels were not associated with 10-year risk of VTE.

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Factor V Leiden Mutation Increases the Risk of Venous Thromboembolism in Cancer Patients – Results From the Vienna Cancer and Thrombosis Study (CATS).

Blood ◽

10.1182/blood.v120.21.2253.2253 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2253-2253

Author(s):

Ingrid Pabinger ◽

Cihan Ay ◽

Daniela Dunkler ◽

Johannes Thaler ◽

Eva-Maria Reitter ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Factor V Leiden ◽

Treatment Modalities ◽

Individual Risk ◽

Factor V ◽

Newly Diagnosed ◽

Factor V Leiden Mutation ◽

Increased Risk ◽

The Impact

Abstract Abstract 2253 Background: Patients with cancer are at an increased risk of venous thromboembolism (VTE). The risk varies markedly in different patient populations and improvement of the prediction of VTE would be of advantage for tailoring thrombosis prophylaxis. Factor V Leiden is the most common genetic risk factor for VTE and the impact of factor V Leiden on cancer-associated thrombosis is not yet fully elucidated. Objective: To study the impact of factor V Leiden on the risk of VTE in cancer patients. Patients and Methods: Nine-hundred-eighty-two patients with newly diagnosed cancer (n=745) or progression of disease after complete or partial remission (n=237) were included in the cancer and thrombosis study (CATS), a prospective observational single centre cohort study at the Medical University Vienna. Patients were followed for a maximum period of 2 years. Blood samples were collected at inclusion and factor V Leiden was determined by genotyping. The main outcome measure was symptomatic or lethal objectively confirmed VTE. All VTE events were adjudicated independently. Results: Of the 982 patients (median age 62 years, interquartile range (IQR) 52–68, 537 men, 445 women) factor V-Leiden was found in 72 (7.3%), 70 had a heterozygous and two a homozygous genotype. Ten of 72 (14%) patients with factor V-Leiden developed VTE, whereas this was the case in 69 of 910 (7.6%) patients without factor V-Leiden. Interestingly, both patients with homozygous factor V Leiden developed VTE. In multivariable analysis that included age, sex, different tumour types, newly diagnosed versus recurrence of disease and the treatment modalities (chemotherapy, radiotherapy and surgery) the hazard ratio (HR) for factor V Leiden was 2.04 (95% confidence interval (CI) 1.04–3.97)). In patients with newly diagnosed tumours the HR for factor V Leiden was 3.7 (95% CI 1.2–12.2) after 30 days. In Kaplan Meier analysis the probability for development of VTE after 6 months was 5.7% in those without and 13% in those with factor V Leiden, after one year the corresponding rates were 7.3% and 15%. Conclusions: Factor V Leiden is a genetically determined and thus disease-independent parameter, which is associated with VTE in cancer patients, especially shortly after cancer diagnosis, and could therefore be used for individual risk assignment. Disclosures: No relevant conflicts of interest to declare.

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A novel variant in GLIS3 is associated with osteoarthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211848 ◽

2018 ◽

Vol 77 (4) ◽

pp. 620-623 ◽

Cited By ~ 13

Author(s):

Elisabetta Casalone ◽

Ioanna Tachmazidou ◽

Eleni Zengini ◽

Konstantinos Hatzikotoulas ◽

Sophie Hackinger ◽

...

Keyword(s):

Complex Disease ◽

Genome Wide Association Study ◽

Total Joint Replacement ◽

Population Based ◽

Uk Biobank ◽

Proteomics Data ◽

Glucose Levels ◽

Genome Wide ◽

A Genome ◽

The Uk

ObjectivesOsteoarthritis (OA) is a complex disease, but its genetic aetiology remains poorly characterised. To identify novel susceptibility loci for OA, we carried out a genome-wide association study (GWAS) in individuals from the largest UK-based OA collections to date.MethodsWe carried out a discovery GWAS in 5414 OA individuals with knee and/or hip total joint replacement (TJR) and 9939 population-based controls. We followed-up prioritised variants in OA subjects from the interim release of the UK Biobank resource (up to 12 658 cases and 50 898 controls) and our lead finding in operated OA subjects from the full release of UK Biobank (17 894 cases and 89 470 controls). We investigated its functional implications in methylation, gene expression and proteomics data in primary chondrocytes from 12 pairs of intact and degraded cartilage samples from patients undergoing TJR.ResultsWe detect a genome-wide significant association at rs10116772 with TJR (P=3.7×10−8; for allele A: OR (95% CI) 0.97 (0.96 to 0.98)), an intronic variant in GLIS3, which is expressed in cartilage. Variants in strong correlation with rs10116772 have been associated with elevated plasma glucose levels and diabetes.ConclusionsWe identify a novel susceptibility locus for OA that has been previously implicated in diabetes and glycaemic traits.

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Use of gastric acid–suppressive agents increases the risk of dementia in patients with upper gastrointestinal disease: A population-based retrospective cohort study

PLoS ONE ◽

10.1371/journal.pone.0249050 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0249050

Author(s):

Hsiu-Chen Lin ◽

Kuan-Tzu Huang ◽

Hsiu-Li Lin ◽

Yow-Sheng Uang ◽

Yi Ho ◽

...

Keyword(s):

Cohort Study ◽

Gastric Acid ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Gastrointestinal Disease ◽

Asian Population ◽

Population Based ◽

Increased Risk ◽

The Impact ◽

Upper Gastrointestinal

Background Prescriptions for gastric acid–suppressive agents, including proton-pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs), are rising. However, little data exist regarding their association with dementia in the Asian population. The objective of this study was thus to investigate the impact of the use of PPIs and H2RAs on the risk of dementia in an Asian population with upper gastrointestinal disease (UGID). Methods We conducted a population-based retrospective cohort study with a 10-year follow-up using data from 2000 to 2015 derived from Taiwan’s Longitudinal Health Insurance Database. We included 6711 patients with UGID receiving gastric acid–suppressive agents, 6711 patients with UGID not receiving agents, and 6711 patients without UGID or treatment thereof, all at least 20 years of age. Groups were matched for age, sex, and index date. The association between gastric acid–suppressive agent use and dementia was analyzed using a Cox proportional hazards regression model adjusted for potential confounders. Results The adjusted hazard ratio (aHR) of dementia for patients with UGID receiving gastric acid–suppressive agents compared with patients with UGID without gastric acid–suppressive agents was 1.470 (95% confidence interval [CI] 1.267–1.705, p < 0.001). Both PPIs and H2RAs increase the risk of dementia (PPIs: aHR 1.886 [95% CI 1.377–2.582], p < 0.001; H2RAs: aHR 1.357 [95% CI 1.098–1.678], p < 0.01), with PPIs exhibiting significantly greater risk (aHR 1.456 [95% CI 1.022–2.075], p < 0.05). Conclusions Our results demonstrate an increased risk of dementia in patients with UGID receiving gastric acid–suppressive agents, including PPIs and H2RAs, and the use of PPIs was associated with a significantly greater risk than H2RA use.

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Global Prospective Cohort Study of Factors Associated with Venous Thromboembolism in Patients with Lung Cancer Receiving Cancer Therapy

Blood ◽

10.1182/blood.v128.22.3590.3590 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3590-3590

Author(s):

Nicole M. Kuderer ◽

Marek S. Poniewierski ◽

Eva Culakova ◽

Gary H. Lyman ◽

Alok A. Khorana ◽

...

Keyword(s):

Lung Cancer ◽

Cohort Study ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Research Funding ◽

Systemic Chemotherapy ◽

Cox Regression ◽

Lung Cancer Patients ◽

Increased Risk ◽

The Impact

Abstract BACKGROUND: Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). However, there have been few studies of risk factors for VTE in lung cancer patients undergoing systemic chemotherapy. METHODS: CANTARISK was a prospective, non-interventional, global cohort study including patients with lung cancer initiating a new chemotherapy regimen. Clinical data were collected at baseline and at 2, 4 and 6 months follow-up. The impact of patient-, disease- and treatment-related factors on the occurrence of VTE in the first 6 months was evaluated in univariable and multivariable Cox regression analyses. RESULTS: A total of 1,980 patients with lung cancer were enrolled from 2011-12 of which 84% were diagnosed with non-small cell lung cancer (NSCLC). Median age was 63 years (range, 25-91) and 63% were male while 82% were active or former smokers. Race was white (70%), Asian (22%), or black (4%) with similar numbers from North America, Europe, and other regions including Asia. Metastatic disease was reported in 70% and ECOG PS was ≥2 in 13%. During the first six months, 121 patients developed a VTE (6.1%), of which 47.1% had pulmonary embolism (PE), 45.5% deep venous thrombosis (DVT), 3.3% catheter-associated thrombosis, and 4.1% visceral thrombosis. Among significant factors in univariable analysis, independent predictors for VTE in multivariable Cox regression analysis included female gender, US geographic region, leg immobilization, and presence of a central venous catheter (Table) with a trend toward greater risk for higher grade histology. Although predictive of early all-cause mortality in this study population (Kuderer et al ASCO 2016), the previously validated risk score for VTE in ambulatory cancer patients (Khorana et al: Blood 2008) was not significantly associated with VTE in either univariable or multivariable analysis. CONCLUSIONS: Several demographic, geographic, and clinical factors are significantly associated with an increased risk of VTE in patients with lung cancer receiving systemic chemotherapy. Future analysis will attempt to assess how novel targeted treatment options might impact the Khorana score's predictive ability across all lung cancer patients. Disclosures Kuderer: Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Lyman:Amgen: Research Funding. Khorana:Bayer: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Halozyme: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.

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Microscopic Colitis and Risk Of Cancer—AA Population-Based Cohort Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa156 ◽

2020 ◽

Cited By ~ 1

Author(s):

David Bergman ◽

Hamed Khalili ◽

Bjorn Roelstraete ◽

Jonas F Ludvigsson

Keyword(s):

Cohort Study ◽

Reference Group ◽

Large Population ◽

Population Based ◽

Microscopic Colitis ◽

First Year ◽

Increased Risk ◽

Risk Of Cancer ◽

The Impact

Abstract Background and Aims The association between microscopic colitis [MC] and cancer risk is unclear. Large, population-based studies are lacking. Methods We conducted a nationwide cohort study of 11 758 patients with incident MC [diagnosed 1990–2016 in Sweden], 50 828 matched reference individuals, and 11 614 siblings to MC patients. Data were obtained through Sweden´s pathology departments and from the Swedish Cancer Register. Adjusted hazard ratios [aHRs] were calculated using Cox proportional hazards models. Results At the end of follow-up [mean: 6.7 years], 1239 [10.5%] of MC patients had received a cancer diagnosis, compared with 4815 [9.5%] of reference individuals (aHR 1.08 [95% confidence interval1.02–1.16]). The risk of cancer was highest during the first year of follow up. The absolute excess risks for cancer at 5, 10, and 20 years after MC diagnosis were + 1.0% (95% confidence interval [CI] 0.4%-1.6%), +1.5% [0.4%-2.6%], and + 3.7% [-2.3–9.6%], respectively, equivalent to one extra cancer event in every 55 individuals with MC followed for 10 years. MC was associated with an increased risk of lymphoma (aHR 1.43 [1.06–1.92]) and lung cancer (aHR 1.32 [1.04–1.68]) but with decreased risks of colorectal (aHR 0.52 [0.40–0.66]) and gastrointestinal cancers (aHR 0.72 [0.60–0.85]). We found no association with breast or bladder cancer. Using siblings as reference group to minimise the impact of shared genetic and early environmental factors, patients with MC were still at an increased risk of cancer (HR 1.20 [1.06–1.36]). Conclusions This nationwide cohort study demonstrated an 8% increased risk of cancer in MC patients. The risk was highest during the first year of follow-up.

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