Risk Of Subsequent Cancer Diagnosis Research Articles

Abstract 2016: Prior Diagnosis Of An Abdominal Aortic Aneurysm Is Associated With An Elevated Risk Of Subsequent Cancer Diagnosis

Background: Epidemiological and mechanistic evidence suggests a potential causal link between cardiovascular disease (CVD) and cancer. Abdominal aortic aneurysms (AAA), a prevalent form of CVD with distinct genetic and biological etiologies, lack clarity regarding cancer risk compared to other CVD types. We conducted a retrospective cohort study using the IBM MarketScan Research Database to investigate whether AAA individuals face an increased cancer risk independent of traditional shared risk factors. Methods: Enrolling individuals aged ≥18 with ≥36 months of continuous coverage between 2008 and 2020, we excluded those with potential Mendelian AAA etiologies, aortic aneurysms with nonspecific anatomic location, or pre-follow-up cancer diagnoses. A subgroup analysis was performed including individuals with Health Risk Assessment records that included smoking status and BMI. We compared three groups: 1) AAA, 2) non-AAA CVD, and 3) no-CVD. Results: The propensity score-matched cohort comprised 68,269 AAA, 136,538 non-AAA CVD, and 136,538 no-CVD individuals. The 5-year cumulative incidence of any cancer was 10.0% (9.7 - 10.3%) in AAA, 7.4% (7.2 - 7.6%) in non-AAA CVD, and 7.4% (7.2 - 7.5%) in no CVD. Time-dependent multivariable-adjusted Cox proportional hazards regression models revealed AAA patients had a higher cancer risk than non-AAA CVD (HR: 1.32; 95% CI: 1.28-1.37; p-value: <0.001) or no CVD (HR: 1.37; 95% CI: 1.32-1.44; p-value: <0.001). Results were consistent after excluding common smoking-related cancers and when adjusting for smoking status and BMI in a subgroup analysis. Conclusions: AAA patients may face a uniquely elevated cancer risk, warranting further mechanistic study and enhanced cancer screening investigations.

Cancer Type and Dementia Diagnosis in Community Dwelling African Americans

AbstractBackgroundCancer and dementia have been reported to have an inverse relationship, suggesting those with cancer may have decreased risk of subsequent dementia, and those with dementia may have a decreased risk of subsequent cancer diagnosis (Zablocka, 2021). However, emerging evidence challenges this idea. A paucity of research exists examining these associations in African Americans, who are twice as likely as whites to develop dementia (Barnes, 2022). Our objective was to examine the association between different types of cancer and dementia risk in community dwelling African Americans.MethodsUsing data from the 2011 National Health and Aging Trends Study (NHATS), a nationally representative sample of Medicare beneficiaries aged 65 and older, we examined the association between cancer type and dementia diagnosis in community dwelling African Americans (n = 1529). Multinomial logistic regression models examined the association between cancer type and dementia diagnosis, controlling for age, sex, and education, as well as anxiety, depression, diabetes, heart disease, and stroke.ResultsResults showed 2.6% of African Americans reported a kidney disease diagnosis, representing 208,107 older adults. Fully adjusted models revealed that African Americans with kidney cancer are over 5 times as likely to have a dementia diagnosis compared to African Americans without kidney cancer [OR: 5.48, p<0.05 (95% CI: 1.24, 24.20]). Other types of cancer (skin, breast, prostate, bladder, ovarian, colon, and “other”) were not significantly associated with increased odds of dementia diagnosis.ConclusionResults show a strong association between kidney cancer and dementia diagnosis in older African Americans, but not other types of cancer. Further research in this area may elucidate reasons for increased dementia risk in African Americans.

Guideline concordance for timely chest imaging after new presentations of dyspnoea or haemoptysis in primary care: a retrospective cohort study

BackgroundGuidelines recommend urgent chest X-ray for newly presenting dyspnoea or haemoptysis but there is little evidence about their implementation.MethodsWe analysed linked primary care and hospital imaging data for patients aged...

Depression Is Associated with an Increased Risk of Subsequent Cancer Diagnosis: A Retrospective Cohort Study with 235,404 Patients.

Background: Depression and cancer share common risk factors and mechanisms of disease. The current literature has not explored the effect of depression on cancer risk. We assessed the difference in cancer risk in patients with and without depression in a large cohort in Germany. Methods: We compared cancer risk and incidence in patients with and without depression aged 18 or above diagnosed between 2015 and 2018 documented in the Disease Analyzer Database. Patients from a comparator group were matched 1:1 to patients with depression based on propensity scores. Patients with previous bipolar disorder (F31), mania (F30) or schizophrenia (F20-29) and cancer diagnosis 3 years prior to index date were excluded. Analyses were stratified by cancer type, age group, and gender. Results: A total of 117,702 patients with depression were included and matched 1:1, resulting in a cohort overall of 235,404. 4.9% of patients with depression compared to 4.1% without depression received at least one cancer diagnosis over 3.9 years median follow-up. The depression group showed an 18% increase in risk for a cancer diagnosis overall, with largest increased risk in lung cancer (HR: 1.39 [1.21-1.60], p < 0.0001), cancers of the gastro-intestinal-tract (HR: 1.30 [1.15-1.46], p < 0.0001), breast (HR: 1.23 [1.12-1.35], p < 0.0001) and urinary (HR: 1.23 [1.06-1.43], p < 0.01). Similarly, the incidence of cancer diagnosis overall increased by 22% for depressed patients. IRs showed no difference across cancer types. Conclusions: Depression increased the risk for cancer diagnosis consistently independent of the comparison method used. The potential mediating factors or shared mechanisms of the disease require further investigation.

Incident cardiovascular events among middle-age men are associated with increased risk of subsequent prostate cancer diagnosis

Abstract Introduction Prostate cancer is the second most common malignancy in men worldwide, but incidence is highly dependent on screening. Purpose We aimed to examine whether incident cardiovascular disease (CVD) events are associated with increased risk of future prostate cancer in middle-aged men. Methods We evaluated asymptomatic self-referred men who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention, or stroke. Study endpoint was the development of cancer during follow up. Cancer and mortality data were available for all subjects from national registries. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event. Results Final study population included 18,282 subjects. Median age was 47 years (Interquartile range [IQR] 41–54). During median follow up time of 12 years (IQR 4–17) 2,047 (11%) subjects developed CVD, 406 (2.2%) developed prostate cancer and 694 (4%) died. Compared with patients who were free of CVD or prostate cancer during follow up, risk of death was 4, 6 and 15 times higher for patients who developed CVD event, prostate cancer, or both during follow up, respectively (p &amp;lt;.001 for all). Time dependent survival analysis showed that subjects who developed CVD during follow up were 60% more likely to develop prostate cancer (95% Confidence Interval [CI] 1.2–2.1, p=.001). However, after multivariable adjustment, this association was no longer significant. Interaction analysis demonstrated that the association of incident CVD with the risk of future cancer diagnosis was age dependent such that in middle-aged men (age≤55 years; N=14,473) incident CVD was associated with a significant 70% increased risk of subsequent cancer diagnosis in multivariable model (95% CI 1.13–2.6, p=.011, p for interaction=.002). Exploratory analysis of men younger than 55 showed that independent association of incident CVD with subsequent cancer diagnosis was different among subjects with normal body mass index (BMI) (≤25 kg/m2) compared with those with increased BMI (HR 0.55; 95% CI [0.22–1.42]; p value=0.23 vs. 1.6; 95% CI [1.007–2.54]; p value=.047; p for interaction=.058, respectively). Conclusion Incident CVD is independently associated with increased risk of subsequent prostate cancer diagnosis among men ≤55 years. Routine prostate cancer surveillance should be considered after CVD event in this population. Funding Acknowledgement Type of funding sources: None.

Incident cardiovascular events among healthy subjects are associated with increased risk of subsequent cancer diagnosis

Abstract Introduction While Cardiovascular disease (CVD) and cancer share common risk factors, data on the temporal association between the occurrence of CVD and cancer is limited. Purpose This study investigated the association between incident CVD events future cancer among apparently healthy subjects. Methods We evaluated asymptomatic self-referred adults who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention, or stroke. Study endpoint was the development of cancer during follow up. Cancer and mortality data were available for all subjects from national registries. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event. Results Final study population included 26,574 subjects. Median age was 46 years (Interquartile range [IQR] 40–53) and 69% were men. During median follow up time of 10 years (IQR 3–16) 2,463 (9%) subjects developed CVD, 2,040 (8%) developed cancer and 869 (3%) died. Most common cancer types were prostate among men (N=406, 2.2%) and breast among women (N=283, 3.4%). Compared with patients who were free of CVD and cancer during follow up, risk of death was 5, 34 and 54 times higher for patients who developed CVD event, cancer, or both during follow up, respectively (p &amp;lt;.001 for all). Time dependent survival analysis showed that subjects who developed CVD during follow up were 50% more likely to develop cancer in a univariate model (95% Confidence Interval [CI] 1.3–1.7, p&amp;lt;.001). Interaction analysis demonstrated that the association of incident CVD with the risk of future cancer diagnosis was age dependent such that in younger subjects (≤52 years; N=19,052) incident CVD was associated with a significant 30% increased risk of subsequent cancer diagnosis (95% CI 1.03–1.67, p=.027) while in older subjects incident CVD was not associated with increased risk of cancer in the multivariable model (p for interaction =.018). Conclusion Incident CVD is independently associated with increased risk of subsequent cancer diagnosis among young adults. Active cancer surveillance should be considered among young patients recovering from a CVD event. Funding Acknowledgement Type of funding sources: None.

Incident cardiovascular events and risk of subsequent cancer diagnosis

Abstract Background Cardiovascular disease (CVD) and cancer share common risk factors. This study investigated the association of CVD diagnosis and the risk of future cancer. Methods We evaluated asymptomatic self-referred adults aged 40–79 years who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention or stroke. Cancer and mortality data were available for all subjects from national registries. Primary end-point was development of cancer during follow up. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event. Results Final study population included 15,486 subjects. Median age was 50 years (Interquartile range [IQR] 44–55) and 72% were men. During median follow up time of 11 years (IQR 6–15) 1,028 (7%) subjects developed CVD, 1,281 (8%) developed cancer and 499 (3%) died. Most common cancer types were prostate among men (N=277, 1.8%) and breast among women (N=187, 1.2%). Time dependent survival analysis showed that subjects who developed CVD during follow up were 60% more likely to develop cancer (95% Confidence Interval [CI] 1.3–1.95, p&amp;lt;0.001). However, after adjustment for known predictors of cancer, the association of incident CVD with cancer diagnosis was no longer significant (p=0.21). Interaction analysis demonstrated that the association of incident CVD with the risk of future cancer diagnosis was age dependent such that in younger subjects (&amp;lt;50 years; N=7,649) incident CVD was associated with a significant 2 fold increased risk of subsequent cancer diagnosis (95% CI 1.2–3.6, p=0.014) while in older subjects incident CVD was not associated with increased risk of cancer in the multivariable model (p for interaction =0.035; Figure 1). Conclusions Incident CVD is independently associated with 2-fold increased risk of subsequent cancer diagnosis among young adults. Our analysis underscores the importance of cancer surveillance among young patients following a CVD event. Figure 1 Funding Acknowledgement Type of funding source: None

Risk of subsequent cancer diagnosis in patients treated with 3D conformal, intensity modulated, or proton beam radiation therapy.

1503 Background: Approximately half of cancer patients receive radiation therapy (RT). Modern RT modalities (3D conformal [3DCRT], intensity modulated [IMRT], proton beam [PBRT]) have been theorized to pose different risks of second cancers, but the relationship between RT modality and subsequent cancers has been unclear due to their rarity. Methods: Pediatric and adult patients with a first cancer diagnosis who received 3DCRT, IMRT, or PBRT were identified in the National Cancer Database. To analyze a more uniform population, cases were required to be non-metastatic and have at least 2 years of follow-up time. Ten cancer types were included: head/neck, upper gastrointestinal (GI), lower GI, gynecological, lymphoma, non-small cell lung, prostate, breast, bone/soft tissue, and brain/central nervous system. Diagnosis of a subsequent cancer was determined using a variable denoting the sequence of malignant neoplasms over the lifetime of the patient. The risk of subsequent cancer diagnosis was modeled using multivariable logistic regression adjusting for age, follow-up time, cancer type, RT dose, chemotherapy, and other factors. Propensity score matching was additionally used to balance baseline characteristics. Results: In total, 430,866 patients were included (33.4% 3DCRT, 65.1% IMRT, 1.5% PBRT) with median follow-up of 5.0 years and total follow-up period of 2.35 million person-years. In the comparison of IMRT relative to 3DCRT, there was no difference in the risk of subsequent cancer diagnosis (adjusted odds ratio [OR] 1.01; 95% confidence interval [CI] 0.98-1.03; p = 0.62). In contrast, recipients of PBRT had significantly lower risk of subsequent cancer diagnosis relative to IMRT (adjusted OR 0.31; 95% CI 0.26-0.37; p &lt; 0.0001). The benefit associated with PBRT persisted in sensitivity analyses that excluded patients with prostate cancer (71.6% of the PBRT cases), receipt of chemotherapy, and/or follow-up time less than 5 years. Conclusions: Risk of subsequent cancer diagnosis was similar between IMRT and 3DCRT and significantly lower for PBRT. PBRT may be preferred in situations where avoidance of second cancers is paramount, such as pediatrics and young adults.

Association between unexplained hypoalbuminaemia and new cancer diagnoses in UK primary care patients.

The association between hypoalbuminaemia and a new diagnosis of cancer is as yet unknown. This study aimed to assess whether unexplained hypoalbuminaemia was associated with an increased risk of subsequent new cancer diagnosis within the next 12 months. A cohort study was performed using a large UK database of adult primary care patients. Patients with a serum albumin test, either low or normal, were followed for 12 months for a new diagnosis of non-skin cancer. Logistic regression was used to assess for relationships between hypoalbuminaemia and cancer diagnoses. A total of 100 122 participants had at least one albumin test result. Of these, 5753 (5.75%) had a result <35g/l, of whom 1634 developed cancer within 12 months. Of the 94 116 patients with normal albumin values, 13 906 developed cancer. Hypoalbuminaemia was associated with an increased risk of subsequent cancer diagnosis within 12 months (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 2.15-2.43). This association was smaller in magnitude after controlling for other conditions known to affect albumin levels (OR: 1.29; 95% CI: 1.12-1.49). Low albumin levels were associated with an increased risk of cancer. This finding needs to be confirmed in other primary care populations.

Unprovoked venous thromboembolism and subsequent cancer risk: a population‐based cohort study

ESSENTIALS: A relationship between unprovoked venous thromboembolism (VTE) and cancer risk was investigated. We collected 27,751 VTE patients and compared them with 110,409 frequency-matched people without VTE. This cohort study showed significantly higher risks of overall and site-specific cancers in the VTE group. There is an increased risk in the first 6 months after VTE, and VTE can be an indicator of occult cancer. We investigated the relationship between unprovoked venous thromboembolism (VTE) and subsequent cancer risk in Taiwan, focusing on both short-term and long-term cancer development. For the case group, we obtained data on 27,751 patients diagnosed with unprovoked VTE between 1 January 1998, and 31 December 2008. For the comparison group, four people without unprovoked VTE were frequency-matched with each unprovoked VTE patient according to age, sex, and index year. Cox proportional hazards regression models were employed to determine the effects of unprovoked VTE on cancer risk. Overall cancer risk was significantly higher in the unprovoked VTE group than in the comparison group (adjusted hazard ratio = 2.26, 95% confidence interval = 2.16-2.37). The increased risk was observed in both men and women in various age groups. The patients in the unprovoked VTE group showed a significantly increased risk of cancer at all site-specific cancer sites. Analyses stratified according to follow-up duration revealed that significant differences were more evident between the two groups over a follow-up duration of < 0.5 years than over a follow-up duration of ≥ 3 years. Furthermore, the 1-year mortality risk of cancer patients with unprovoked VTE was significantly higher than that for cancer patients in the non-VTE group. The results of this study show that unprovoked VTE is associated with a consistently high risk of subsequent cancer diagnosis. This is particularly true in the first 6 months after VTE. It suggests that unprovoked VTE can be an indicator of occult malignancy.

Limited screening with versus without 18F-fluorodeoxyglucose PET/CT for occult malignancy in unprovoked venous thromboembolism: an open-label randomised controlled trial

Clear guidelines for the investigation of occult malignancy after unprovoked venous thromboembolism are not yet available. (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT could serve as a comprehensive screening strategy for occult malignancy in this context. We aimed to compare a screening strategy based on (18)F-FDG PET/CT with a limited screening strategy for detection of malignant disease in patients with unprovoked venous thromboembolism. In an open-label, multicentre, randomised study we enrolled patients from four French university hospitals. Patients aged 18 years or older, diagnosed with unprovoked venous thromboembolism (not provoked by a major inherited or acquired risk factor) were invited to participate. Patients were randomly assigned in a 1:1 ratio to a limited screening strategy (physical examination, usual laboratory tests, and basic radiographs) or a screening strategy consisting of the limited strategy plus an (18)F-FDG PET/CT scan. Randomisation was done with a dedicated central web-based randomisation system, in block sizes of six, stratified by centre, and concealed from the investigators. Patients and investigators were not masked to study group assignment. Patients were followed up for 2 years. The primary outcome was the proportion of patients with a cancer diagnosis in each group after the initial screening assessment. Analyses were conducted in modified intention-to-test and per-protocol populations. This trial is completed and registered with ClinicalTrials.gov, number NCT00964275. Between March 3, 2009, and Aug 18, 2012, we enrolled and randomly assigned 399 patients; five withdrew consent, leaving 197 in each group for the modified intention-to-test analysis. After initial screening assessment, cancer was diagnosed in 11 (5·6%) patients in the (18)F-FDG PET/CT group and four (2·0%) patients in the limited screening group (absolute risk difference 3·6%, 95% CI -0·4 to 7·9; p=0·07). At the initial screening assessment, seven (64%) of the 11 cancers diagnosed in the (18)F-FDG PET/CT group were early-stage compared with two of four cancers diagnosed in the limited screening group (p=1·00). One (0·5%) occult malignancy was detected in 186 patients who had negative initial screening in the (18)F-FDG PET/CT group, compared with nine (4·7%) in 193 patients in the limited screening group (absolute risk difference 4·1%, 95% CI 0·8 to 8·4, p=0·01). Overall, five (42%) of the 12 cancers diagnosed in the (18)F-FDG PET/CT group were advanced stage, compared with seven (54%) of the 13 cancers diagnosed in the limited screening group (p=0·70). 16 patients died during follow-up, eight (4·1%) in each group. Two (1·0%) patients in the (18)F-FDG PET/CT group and five (2·5%) in the limited screening group had cancer-related deaths. A strategy including limited screening and a (18)F-FDG PET/CT was not associated with a significantly higher rate of cancer diagnosis after unprovoked venous thromboembolism. The risk of subsequent cancer diagnosis was, however, lower in patients who had negative initial screening that included (18)F-FDG PET/CT than in patients who had negative initial limited screening. Whether or not (18)F-FDG PET/CT might be useful in a more selected population of patients with a high risk of cancer remains to be determined. Programme Hospitalier de Recherche Clinique (French Department of Health).