Cardiovascular disease risks among head and neck cancer survivors in a large, population-based cohort study.

Wei, Mei; Hashibe, Mia; Abdelaziz, Sarah; Hunt, Jason P.; Buchmann, Luke; Rowe, Kerry; Synder, John; Wan, Yuan; Deshmukh, Vikrant; Newman, Michael G.; Fraser, Alison; Herget, Kim; Monroe, Marcus M.

doi:10.1200/jco.2018.36.15_suppl.6051

Cited by 3 publications

(4 citation statements)

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“…A lookup in the BIOS QTL Browser (https://genenetwork.nl/biosqtlbrowser/) confirms 20 cis-expression quantitative trait methylations (eQTMs) showing evidence of correlation between gene expression and methylation at this locus in whole blood, though further work evaluating tissue-specific expression is required. The role of this gene in cardiac function is of interest since cardiovascular disease is a common comorbidity of people with HNC [46,47], where the 5-year incidence of non-cancer survival is 13% [48]. Our finding may have clinical relevance for OPC and prognostic studies more broadly if methylation and/ or expression of SPEG is confirmed to be causally related to with survival.…”

Section: Discussionmentioning

confidence: 71%

Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer

et al. 2020

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Background: Smoking status, alcohol consumption and HPV infection (acquired through sexual activity) are the predominant risk factors for oropharyngeal cancer and are thought to alter the prognosis of the disease. Here, we conducted single-site and differentially methylated region (DMR) epigenome-wide association studies (EWAS) of these factors, in addition to ∼ 3-year survival, using Illumina Methylation EPIC DNA methylation profiles from whole blood in 409 individuals as part of the Head and Neck 5000 (HN5000) study. Overlapping sites between each factor and survival were then assessed using two-step Mendelian randomization to assess whether methylation at these positions causally affected survival. Results: Using the MethylationEPIC array in an OPC dataset, we found novel CpG associations with smoking, alcohol consumption and~3-year survival. We found no CpG associations below our multiple testing threshold associated with HPV16 E6 serological response (used as a proxy for HPV infection). CpG site associations below our multiple-testing threshold (P Bonferroni < 0.05) for both a prognostic factor and survival were observed at four gene regions: SPEG (smoking), GFI1 (smoking), PPT2 (smoking) and KHDC3L (alcohol consumption). Evidence for a causal effect of DNA methylation on survival was only observed in the SPEG gene region (HR per SD increase in methylation score 1.28, 95% CI 1.14 to 1.43, P 2.12 × 10 −05). Conclusions: Part of the effect of smoking on survival in those with oropharyngeal cancer may be mediated by methylation at the SPEG gene locus. Replication in data from independent datasets and data from HN5000 with longer follow-up times is needed to confirm these findings.

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Section: Discussionmentioning

confidence: 71%

Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer

et al. 2020

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“…In particular, multiple large population-based studies have shown that cardiovascular (CV) disease (CVD) is the leading noncancer cause of morbidity and mortality in patients with HNSCC . Patients in the US who receive a diagnosis of HNSCC have a more than 3-fold higher incidence of developing CVD, including acute myocardial infarction (MI), during the first 2 years after diagnosis compared with matched individuals without cancer . A SEER-Medicare analysis of more than 6000 patients older than 65 years with HNSCC treated with radiotherapy from 1992 and 2002 reported up to a 34% 10-year incidence of cerebrovascular events .…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6] Patients in the US who receive a diagnosis of HNSCC have a more than 3-fold higher incidence of developing CVD, including acute myocardial infarction (MI), during the first 2 years after diagnosis compared with matched individuals without cancer. 7 A SEER-Medicare analysis of more than 6000 patients older than 65 years with HNSCC treated with radiotherapy from 1992 and 2002 reported up to a 34% 10-year incidence of cerebrovascular events. 8 A large study from Korea found that the risks of MI and stroke were 38% and 48% higher, respectively, in patients with head and neck cancer compared with noncancer controls.…”

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confidence: 99%

Risk of Cardiovascular Events Among Patients With Head and Neck Cancer

Sun

Brody

Candelieri

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportanceCardiovascular (CV) disease is a substantial cause of morbidity and mortality in cancer due to shared risk factors and exposure to potentially cardiotoxic cancer therapy. However, our understanding of CV risk in patients with head and neck squamous cell carcinoma (HNSCC) is limited.ObjectiveTo define CV risk profiles, incident stroke, myocardial infarction (MI), and mortality in patients with HNSCC.Design, Setting, ParticipantsThis retrospective, population-based cohort study included 35 897 US veterans with newly diagnosed HNSCC from January 1, 2000, to December 31, 2020. Data were analyzed from May 2022 to January 2023.ExposuresDemographic, cancer-specific, and treatment characteristicsMain OutcomesPrevalence of CV risk factors, medication use, and control at HNSCC diagnosis; cumulative incidence of stroke and MI; and all-cause death.ResultsOf 35 857 US veterans with HNSCC (median [IQR] age, 63 [58-69] years; 176 [0.5%] American Indian or Alaska Native, 57 [0.2%] Asian, 5321 [16.6%] Black, 207 [0.6%] Native Hawaiian or Other Pacific Islander, and 26 277 [82.0%] White individuals), there were high rates of former or current smoking (16 341 [83%]), hypertension (24 023 [67%]), diabetes (7988 [22%]), and hyperlipidemia (18 421 [51%]). Although most patients were taking risk-lowering medications, 15 941 (47%) had at least 1 uncontrolled CV risk factor. Black race was associated with increased risk of having uncontrolled CV risk factor(s) (relative risk, 1.06; 95% CI, 1.03-1.09), and patients with larynx cancer had higher rates of prevalent and uncontrolled risk factors compared with other cancer subsites. Considering death as a competing risk, the 10-year cumulative incidence of stroke and MI was 12.5% and 8.3%, respectively. In cause-specific hazards models, hypertension, diabetes, carotid artery stenosis, coronary artery disease, and presence of uncontrolled CV risk factor(s) were significantly associated with stroke and MI. In extended Cox models, incident stroke and MI were associated with a 47% (95% CI, 41%-54%) and 71% (95% CI, 63%-81%) increased risk of all-cause death, respectively.ConclusionThe results of this cohort study suggest that in HNSCC, the burden of suboptimally controlled CV risk factors and incident risk of stroke and MI are substantial. Modifiable CV risk factors are associated with risk of adverse CV events, and these events are associated with a higher risk of death. These findings identify populations at risk and potentially underscore the importance of modifiable CV risk factor control and motivate strategies to reduce CV risk in HNSCC survivorship care.

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“…HNC and CVD have similar risk factors such as male sex, low fruit and vegetable intake, and tobacco and alcohol use [ 6 ]. In HNC patients, the prevalence rates of carotid artery disease and any CVD, which can possibly be underestimated, are 3% and 26%, respectively [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Application of Carotid Duplex Ultrasonography in the Surveillance of Carotid Artery Stenosis after Neck Irradiation

Kuo¹,

Wu²,

Hsieh³

et al. 2022

Rev. Cardiovasc. Med.

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Head and neck cancer (HNC) shares some risk factors with cardiovascular disease. Neck radiotherapy (RT) causes carotid artery injury and stenosis. In HNC patients treated with RT, the prevalence rate of severe (>70%) carotid artery stenosis is >10%, and the cumulative incidence continuously increases over time. There is at least a two-fold risk of cerebrovascular events in these patients compared with the normal population. Carotid artery stenosis is mainly assessed and diagnosed via duplex ultrasonography. Angioplasty and stenting may be recommended to patients who developed severe post-irradiation carotid artery stenosis. This review assessed Taiwanese data that provided some recommendations for HNC patients treated with RT. With consideration of the high prevalence rate of carotid artery stenosis after neck irradiation, duplex ultrasonography should be included in the follow-up workup.

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Cardiovascular disease risks among head and neck cancer survivors in a large, population-based cohort study.

Cited by 3 publications

References 0 publications

Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer

Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer

Risk of Cardiovascular Events Among Patients With Head and Neck Cancer

Application of Carotid Duplex Ultrasonography in the Surveillance of Carotid Artery Stenosis after Neck Irradiation

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