Risk Factor For Incident Cancer Research Articles

Abstract 9271: Risk of Cancer After Diagnosis of Cardiovascular Disease

Introduction: Cardiovascular disease (CVD) and cancer share several known risk factors. While preclinical models have found that various types of CVD can accelerate cancer progression, clinical studies have not determined whether these associations are due to shared risk factors or a specific impact of atherosclerosis on cancer development. Hypothesis: CVD, particularly atherosclerotic CVD, is an independent risk factor for incident cancer. Methods: We used a 1:1 matched retrospective cohort study using IBM’s MarketScan insurance claims database from 2009 to 2019. Those with CVD were stratified as having either atherosclerotic (aCVD) or non-atherosclerotic disease (naCVD). Those with prior diagnostic codes for cancer were excluded. Cumulative risks of (1) any incident cancer, (2) organ-specific cancers according to CVD groups. Kaplan-Meier and multivariable adjusted Cox proportional hazards (PH) models with propensity score adjustment were used to evaluate the association of CVD groups and cancer. Results: Among 4,487,412 matched (1:1 no CVD vs. CVD) individuals, the mean age was 56 years, 48% were female, 31% had aCVD, and 19% had naCVD. Those without CVD had a 5-year cumulative cancer incidence of 5.4% (95% CI, 5.3%-5.4%), compared to 6.8% (95% CI, 6.7%-6.8%) among those with any CVD and 7.7% (95% CI, 7.6%-7.8%) for those with aCVD. After multivariable and propensity score adjustment, individuals with CVD were found to have a significantly increased risk of incident cancer compared to individuals without CVD (hazard ratio [HR], 1.14; 95% CI, 1.13-1.15). Those with aCVD had a significantly higher risk of cancer compared to the naCVD group (HR, 1.03; 95% CI, 1.02-1.05). These findings were consistent in sensitivity analyses which were further adjusted for smoking history and body mass index. Cancer subtype analyses showed a specific association of aCVD with lung, bladder, liver, brain, and other hematologic cancers. Conclusions: In this retrospective cohort study, individuals with CVD had an increased risk of incident cancer compared to those without CVD. This association may be driven by the relationship of aCVD with specific cancer subtypes, which persists after controlling for conventional risk factors.

Cancer risk in severe alpha-1-antitrypsin deficiency.

Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is a risk factor for pulmonary emphysema and liver disease, but its effect on cancer risk is unknown. Our aim was to evaluate the risk and the risk factors for incident cancer in PiZZ individuals compared with the general population with known smoking habits. A longitudinal study of PiZZ individuals (n=1595) from the Swedish National AATD Register, and controls (n=5999) from Swedish population-based cohorts. Data on cancer and mortality were obtained by cross-linkage with national registers. Individuals who had undergone lung transplantation (n=10) and those with a cancer diagnosis within 5 years prior to inclusion (n=63) were excluded. The risk factors for developing cancer were analysed using proportional hazards and Fine-Gray regression models, adjusting for age, sex, smoking habits and the presence of liver disease. The median follow-up time was 17 years (interquartile range 11 years) for the whole study population. The incidence rates of hepatic and non-hepatic cancer per 1000 person-years were 1.6 (95% CI 1.1-2.3) and 8.5 (95% CI 7.2-10.0), respectively, for the PiZZ individuals, and 0.1 (95% CI 0.04-0.2) and 6.6 (95% CI 6.0-7.1), respectively, for the controls. The adjusted hazard ratios for hepatic and for non-hepatic cancer were 23.4 (95% CI 9.9-55.4) and 1.3 (95% CI 1.1-1.5), respectively, in the PiZZ individuals compared with the controls. These results suggest that individuals with severe AATD may have an increased risk of developing both hepatic and non-hepatic cancer, compared with the general population.

Is Heart Failure a New Risk Factor for Incident Cancer?

OPINION article Front. Cardiovasc. Med., 07 February 2022Sec. Heart Failure and Transplantation Volume 9 - 2022 | https://doi.org/10.3389/fcvm.2022.828290

The association between heart failure and incident cancer in women: an analysis of the Women's Health Initiative.

There is conflicting evidence whether heart failure (HF) is a risk factor for incident cancer. Despite population-based cohorts demonstrating this association, an analysis of the Physician's Health Study found no association in a cohort of mostly healthy males. We investigated the association of HF with incident cancer among a large cohort of post-menopausal women. A prospective cohort study of 146 817 post-menopausal women age 50 to 79 years enrolled in the Women's Health Initiative from 1993-1998, and followed through 2015. The primary exposure was adjudicated incident HF diagnosis, including preserved and reduced ejection fraction in a sub-cohort. The primary outcome was adjudicated incident total and site-specific cancers. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazard regression models. Over a median follow-up of 8.4 years, 3272 and 17 474 women developed HF and cancer, respectively. HF developed in 235 women prior to cancer. HF was associated with subsequent incident cancer [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.11-1.48]. Associations were observed for obesity-related cancers (HR 1.24, 95% CI 1.02-1.51), as well as lung and colorectal cancers (HR 1.58, 95% CI 1.09-2.30 and HR 1.52, 95% CI 1.02-2.27, respectively). HF with preserved ejection fraction (HR 1.34, 95% CI 1.06-1.67), but not HF reduced ejection fraction (HR 0.99, 95% CI 0.74-1.34), was associated with total cancer. Heart failure was associated with an increase in cancer diagnoses in post-menopausal women. This association was strongest for lung cancer. Further research is needed to appreciate the underlying mechanisms responsible for this association.

2153The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease; a cohort study

Abstract Background Chronic systemic low-grade inflammation, measured by elevated plasma concentrations of high sensitive C-reactive Protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that systemic low-grade inflammation is also related to a higher risk of cancer. Purpose In the present prospective cohort study the relation between systemic low-grade inflammation and risk of cancer was evaluated in patients with clinically manifest vascular disease. Methods In total 7178 patients from the SMART cohort with manifest cardiovascular disease and plasma CRP levels ≤10 mg/L were included. Data of the cohort were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident cardiovascular disease as well as incident cancer. Cancer types were classified according to anatomical location of origin, as well as histopathological subtype, irrespective of their anatomical location of origin. To adjust for potential confounding, age, sex, smoking status, packyears of smoking, and body mass index were added to the models, and additional cardiovascular risk factors, including diabetes mellitus, and systolic blood pressure. Results After a median follow-up time of 8.3 years (interquartile range 4.6–12.3) 1289 recurrent cardiovascular events (myocardial infarction, stroke, or vascular mortality) and 1072 incident cancer diagnoses were observed. CRP level was related to recurrent cardiovascular disease risk (HR 1.57; 95% CI 1.35–1.82) (Figure 1A), as well as risk of CVD and/or cancer (HR 1.45; 95% CI 1.29–1.62) (Figure 1B) comparing the third tertile of CRP to the first tertile. CRP concentration was related to total cancer risk (HR 1.33; 95% CI 1.13–1.55 for the third tertile of CRP compared to the first tertile) (Figure 1C). Especially incident lung cancer, independent of histopathological subtype, was related to CRP level (HR 2.64; 95% CI 1.77–3.93 for the third tertile of CRP compared to the first) (Figure 1D). No effect modification by smoking status or years of smoking cessation was observed of the relation between CRP and lung cancer (p-values for interaction >0.05). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of their anatomical location of origin (HR 1.17; 95% CI 1.08–1.27, and HR 1.11; 95% CI 1.02–1.20 for 1 mg/L higher CRP level respectively). Sensitivity analyses accounting for reverse causality by excluding patients with a cancer diagnosis within 1 and within 2 years of follow up showed similar results. Kaplan Meier curves per CRP tertile Conclusion Chronic systemic low-grade inflammation, measured by plasma CRP levels ≤10mg/L, is a risk factor for incident cancer, markedly lung cancer, independent of smoking status, in patients with stable cardiovascular disease.

The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study

AimsLow-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD.Methods and resultsIn total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6–12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10–1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02–5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05).ConclusionChronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.

Cancer Risk in Inflammatory Bowel Disease: A 6-Year Prospective Multicenter Nested Case–Control IG-IBD Study

In a 6-year, multicenter, prospective nested case-control study, we aimed to evaluate risk factors for incident cancer in inflammatory bowel disease (IBD), when considering clinical characteristics of IBD and immunomodulator use. The secondary end point was to provide characterization of incident cancer types. All incident cases of cancer occurring in IBD patients from December 2011-2017 were prospectively recorded in 16 Italian Group for the Study of Inflammatory Bowel Disease units. Each of the IBD patients with a new diagnosis of cancer was matched with 2 IBD patients without cancer, according to IBD phenotype (ulcerative colitis [UC] vs Crohn's disease [CD]), age (±5 years), sex. Risk factors were assessed by multivariate logistic regression analysis. Cancer occurred in 403 IBD patients: 204 CD (CD cases), 199 UC (UC cases). The study population included 1209 patients (403 IBD cases, 806 IBD controls). Cancer (n = 403) more frequently involved the digestive system (DS; 32%), followed by skin (14.9%), urinary tract (9.7%), lung (6.9%), genital tract (6.5%), breast (5.5%), thyroid (1.9%), lymphoma (2.7%, only in CD), adenocarcinoma of the small bowel (SBA; 3.9%, 15 CD, 1 pouch in UC), other cancers (15.9%). Among cancers of the DS, colorectal cancer (CRC) more frequently occurred in UC (29% vs 17%; P < 0.005), whereas SBA more frequently occurred in CD (13% vs 6.3% P = 0.039). In CD, perforating (B3) vs non-stricturing non-perforating (B1) behavior represented the only risk factor for any cancer (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.33-4.11). In CD, risk factors for extracolonic cancer (ECC) were a B3 vs B1 and a stricturing (B2) vs B1 behavior (OR, 2.95; 95% CI, 1.62-5.43; OR, 1.79; 95% CI, 1.09-2.98). In UC, risk factors for ECC and for overall cancer were abdominal surgery for UC (OR, 4.63; 95% CI, 2.62-8.42; OR, 3.34; 95% CI, 1.88-5.92) and extensive vs distal UC (OR, 1.73; 95% CI, 1.10-2.75; OR, 1.99; 95% CI, 1.16-3.47). Another risk factor for ECC was left-sided vs distal UC (OR, 1.68; 95% CI, 1.00-2.86). Inflammatory bowel disease duration was a risk factor for skin and urinary tract cancers. Perforating CD, extensive UC, and abdominal surgery for UC were identified as risk factors for overall incident cancer and for ECC. The clinical characteristics associated with severe IBD may increase cancer risk.

P802 Perforating Crohn's Disease and pancolitis as risk factors for incident cancer: a prospective multi-centre nested case–control IG-IBD study at 6 years

P802 Perforating Crohn's Disease and pancolitis as risk factors for incident cancer: a prospective multi-centre nested case–control IG-IBD study at 6 years

Heart Failure Stimulates Tumor Growth by Circulating Factors.

Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer. HF was induced by inflicting large anterior myocardial infarction in APCmin mice, which are prone to developing precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was used in which an infarcted or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post-myocardial infarction proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and patients with HF. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large, prospective general population cohort. The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4-fold in APCmin mice (all P<0.0001). The severity of left ventricular dysfunction and fibrotic scar strongly correlated with tumor growth ( P=0.002 and P=0.016, respectively). We identified several proteins (including serpinA3 and A1, fibronectin, ceruloplasmin, and paraoxonase 1) that were elevated in human patients with chronic HF (n=101) compared with healthy subjects (n=180; P<0.001). Functionally, serpinA3 resulted in marked proliferation effects in human colon cancer (HT-29) cells, associated with Akt-S6 phosphorylation. Finally, elevated cardiac and inflammation biomarkers in apparently healthy humans (n=8319) were predictive of new-onset cancer (n=1124) independently of risk factors for cancer (age, smoking status, and body mass index). We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.

Risk of Malignant Cancer Among Women With New-Onset Atrial Fibrillation.

A substantial proportion of patients with atrial fibrillation (AF) die of noncardiovascular causes, and recent studies suggest a link between AF and cancer. To evaluate the associations between AF and cancer in a large, long-term prospective cohort study. In this cohort study, a total of 34 691 women 45 years or older and free of AF, cardiovascular disease, and cancer at baseline were prospectively followed up between 1993 and 2013, for incident AF and malignant cancer within the Women's Health Study, a randomized clinical trial of aspirin and vitamin E for the prevention of cardiovascular disease and cancer. Cox proportional hazards models using time-updated covariates were constructed to assess the association of new-onset AF with subsequent cancer and to adjust for potential confounders. Data analysis was performed from December 2014 to May 2015. New-onset AF. Incident malignant cancer confirmed by an end point committee. During a median follow-up of 19.1 years of 34 691 study participants (interquartile range [IQR], 17.6-19.7 years), new-onset AF and malignant cancer were confirmed among 1467 (4.2%) and 5130 (14.8%) participants, respectively. Median age at baseline among participants with new-onset AF and new-onset cancer during follow-up was 58 years (IQR, 52-64 years) and 55 years (IQR, 50-61 years), respectively. Atrial fibrillation was a significant risk factor for incident cancer in age-adjusted (hazard ratio [HR], 1.58; 95% CI, 1.34-1.87; P < .001) and multivariable-adjusted (HR, 1.48; 95% CI, 1.25-1.75; P < .001) models. The relative risk of cancer was highest in the first 3 months after new-onset AF (HR, 3.54; 95% CI, 2.05-6.10; P < .001) but remained significant beyond 1 year after new-onset AF (adjusted HR, 1.42; 95% CI, 1.18-1.71; P < .001), and a trend toward an increased cancer mortality was observed (adjusted HR, 1.32; 95% CI, 0.98-1.79; P = .07). In contrast, among women with new-onset cancer, the relative risk of AF was increased only within the first 3 months (HR, 4.67; 95% CI, 2.85-7.64; P < .001) but not thereafter (HR, 1.15; 95% CI, 0.95-1.39; P = .15). In this large, initially healthy cohort, women with new-onset AF had an elevated cancer risk beyond 1 year of AF diagnosis. Shared risk factors and/or common systemic disease processes might underlie this association.

Abstract 11875: Risk of Malignant Cancer Among Women With New-onset Atrial Fibrillation

Introduction: A substantial proportion of patients with atrial fibrillation (AF) die of non-cardiovascular causes, and recent studies suggest a link between AF and cancer. However, this association has not been evaluated in long-term prospective studies. Methods: A total of 34691 women ≥45 years and free of AF, cardiovascular disease and cancer at baseline were prospectively followed for incident AF and malignant cancer within the Women’s Health Study. All incident AF and cancer events were validated by medical record review. Cox proportional-hazards models using time-updated covariates were constructed to assess the relationship of new-onset AF with incident cancer and to adjust for potential confounders. We then assessed the risk of incident AF among women with cancer using a similar modelling approach. Results: Mean age at baseline was 55±7 years. During 19.1 years of follow-up, we observed 1467 (4.2%) AF and 5130 (14.8%) cancer events. AF was a significant risk factor for incident cancer in age-adjusted (hazard ratio (HR) 1.58, 95% confidence interval (CI), 1.34, 1.87, p&lt;0.0001) and multivariable adjusted (HR 1.49, 95% CI, 1.26, 1.77, p&lt;0.0001) models, and was increased among women with paroxysmal (HR 1.35, 95% CI 1.09, 1.67, p=0.005) and non-paroxysmal AF (HR 1.61, 95% CI 1.23, 2.09, p=0.0004). The risk of cancer was highest in the first 3 months after new-onset AF (HR 3.53, 95% CI 2.05, 6.08, p&lt;0.0001) but remained significant beyond 1 year (adjusted HR 1.44, 95% CI 1.19, 1.73, p=0.0001). New-onset AF was also associated with an increased risk of cancer mortality (adjusted HR 1.37, 95% CI 1.01, 1.85, p=0.04). In contrast, women with new-onset cancer had an increased risk of incident AF within 3 months (HR 4.61, 95% CI 2.81, 7.54, p&lt;0.0001) but not beyond 1 year (HR 1.17, 95% CI 0.97, 1.41, p=0.11). Conclusions: In this large cohort of initially healthy women, new-onset AF was a significant risk factor for the short and long term diagnosis of incident cancer. In contrast, cancer was not associated with an increased AF risk over the long term. Our results may suggest that AF could be an early sign of occult cancer or an underlying systemic process conferring an increased cancer risk.

The Role of Inflammation in Mediating Risk for Medical Disorders in Depressed Patients

Depression, cancer, and cardiovascular disease are highly comorbid and prevalent medical conditions that account for leading causes of disability and mortality worldwide. Increasing evidence suggests that chronic inflammation plays a critical role in the pathogenesis and interplay of these conditions. Notably, chronic depression is an independent risk factor for incident cancer and cardiovascular disease, and is associated with disease progression and increased mortality. Successful depression treatment is associated independently with normalization of systemic proinflammatory cytokine levels and improved medical outcome. This article highlights the studies that identify depression as an independent risk factor for cancer and cardiovascular disease, and discusses the inflammatory-mediated biological mechanisms by which depression is hypothesized to influence the progression and outcome of these medical conditions. Research regarding the efficacy and impact of depression treatment on the medical outcome are also discussed. [ Psychiatr Ann . 2015;45(5):249–254.]

Evaluation of C-reactive protein and YKL-40 as risk factors for incident cancer and early death after a diagnosis of cancer.

1531 Background: Elevated plasma levels of C-reactive protein (CRP) and YKL-40 are each associated with increased risk of cancer in the general population and with early death in patients with canc...