Principal Investigator: Dr Nirmala Bhoo Pathy
Department: Social and Preventive Medicine
University of Malaya, Social and Preventive Medicine, Faculty of Medicine, Lembah Pantai, 50603 Kuala Lumpur, MalaysiaTags: 13462, adjuvant therapy, cancer, cardiovascular disease, survival
1a: Cancer therapy-induced cardiotoxicity is the leading cause of treatment-associated mortality among cancer survivors. Anticancer therapies may interact with pre-existing cardiovascular risk factors and accentuate cardiovascular morbidity among cancer survivors.
We aim to determine:
- Prevalence of cardiovascular risk factors in cancer patients
- Impact of pre-existing cardiovascular risk factors on cancer survival
- The extent to which cancer therapy, ethnicity, socioeconomic status, and lifestyle, modifies the association between pre-existing cardiovascular risk factors and cancer survival
- Association between cancer therapy and risk of hypertension, diabetes, stroke and cardiovascular disease among cancer survivors without concurrent comorbidities
1b: UKBIOBANK aims to improve the prevention, diagnosis and treatment of life-threatening illnesses including cancer. Knowledge on baseline cardiovascular risk profile and competing mortality risks in cancer patients (cardiovascular mortality versus cancer mortality) will aid tailoring of cancer therapy. In patients with considerable risk of developing cardiovascular disease, physicians may be able to choose adjuvant cancer therapies with higher cardiac safety profile. Furthermore, it will be highly relevant to determine for which patients with cancer will preventive cardiovascular intervention, lead to meaningful reduction in late cardiac complications, and mortality. This research will improve management of cancer patients and their survival.
1c: Linkage between UK Biobank and cancer registries allows identification of participants with newly diagnosed cancers. The baseline presence of cardiovascular risk factors (diabetes, hypertension, hypercholesterolemia, obesity, smoking, and family history of premature coronary heart disease) will be determined in these patients.
Subsequent linkage with death registries will allow estimation of overall and disease-specific survival of cancer survivors. Linkage with primary care data and in-patient hospital admissions data will enable assessment of incidence of hypertension, diabetes, stroke and coronary heart disease in these survivors.
We will compare the survival of cancer patients with cardiovascular risk factors against those without.
1d: We intend to include all participants of the UK Biobank cohort with either prevalent, or incident cancers.
Lead Collaborators: 1) Michael O’Rorke
Collaborating Institutions and Addresses: 1) Queen’s University Belfast, Centre for Public Health, ICS-B, RVH Site, Grosvenor Road, Belfast BT12 6BJ, United Kingdom
Project Extension Text:
This study examines cancer therapy-induced cardiotoxicity and cardiovascular morbidity among cancer survivors. Importantly, the major cardiovascular diseases, including coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF) and congenital heart disease (CHD), are caused by multiple genetic and environmental factors, as well as the interactions between them 1, 2.
In the past two decades, much effort has been undertaken to understand the genes and specific DNA sequence variants responsible for this heritability. For example, several genome-wide association studies have identified a number of novel loci (13 SNPs) associated with myocardial infarction 3 with close to 60 common SNPs associated with coronary artery disease risk 4. These data have been used to create genetic risk scores and prognostic indices that can improve prediction beyond adjustment for conventional risk factors 3.
Whilst we know that factors such as the metabolic syndrome, smoking and co-morbidity contribute to cardiovascular disease risk, there are indications of individual variation of susceptibility to cancer treatment-related toxicity and variation of genetic susceptibility for radiation-related cardiovascular disease 5, 6. It is therefore important that we attempt to adjust for specific genes and DNA sequence variants among cancer survivors, as genetic predisposition may also alter individual risk for cardiovascular mortality and morbidity post-diagnosis.
We plan to use the UK Biobank Axiom® array testing to adjust for the risk of potential cardiovascular predisposition, targeting genetic markers of specific interest identified from empirical literature. We believe that an examination of the genetic data may be a good use of our interim study resources whilst we await release of the UK biobank biomarker data and subsequent examination of our planned cardiac biomarkers for this project.
1. Kaynak B, Wang Q, Mebus S, et al: Genome-Wide Array Analysis of Normal and Malformed Human Hearts [Internet]. Circulation 107:2467–2474, 2003[cited 2017 Jun 2] Available from: http://circ.ahajournals.org/cgi/doi/10.1161/01.CIR.0000066694.21510.E2
2. Kathiresan S, Srivastava D: Genetics of human cardiovascular disease. [Internet]. Cell 148:1242–57, 2012[cited 2017 Jun 2] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22424232
3. Thanassoulis G, Vasan RS: Genetic Cardiovascular Risk Prediction: Will We Get There? [Internet]. Circulation 122:2323–2334, 2010[cited 2017 Jun 2] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21147729
4. McPherson R, Tybjaerg-Hansen A: Genetics of Coronary Artery Disease [Internet]. Circ Res 118:564–578, 2016[cited 2017 Jun 2] Available from: http://www.ncbi.nlm.nih.gov/pubmed/26892958
5. Hilbers FSM, Boekel NB, van den Broek AJ, et al: Genetic variants in TGFβ-1 and PAI-1 as possible risk factors for cardiovascular disease after radiotherapy for breast cancer. [Internet]. Radiother Oncol 102:115–21, 2012[cited 2017 Jun 2] Available from: http://linkinghub.elsevier.com/retrieve/pii/S0167814011006293
6. Aleman BMP, Moser EC, Nuver J, et al: Cardiovascular disease after cancer therapy. [Internet]. EJC Suppl EJC Off J EORTC, Eur Organ Res Treat Cancer . [et al] 12:18–28, 2014[cited 2017 Jun 2] Available from: http://www.ncbi.nlm.nih.gov/pubmed/26217163