As the use of genetic testing increasingly impacts patient outcomes, the role of general practitioners (GPs) in the identification and care of patients at high risk for hereditary cancer becomes even more important. A GP-led model of surveillance provides a convenient and accessible platform to support adherence to screening strategies.
The past decade has seen great strides in our understanding of the genetic basis of human disease. Arguably, the most profound impact has been in the area of cancer genetics, where cancer genes with high-penetrance familial pathogenic variants are increasingly identified. These insights have paved the way for the integration of genetics into mainstream cancer care.
Understanding the hereditary cancer predisposition syndrome that underlies one’s personal and/or family history realises the potential of gene-directed cancer prevention, management and treatment.
Currently, over 400 hereditary cancer predisposition syndromes have been identified, most of which have an autosomal dominant inheritance pattern. Although many of these are rare syndromes, they account for at least 5–10% of all cancer incidence
A hereditary cancer predisposition syndrome is usually suspected in families with the following characteristics
However, due to phenotypic variability, incomplete penetrance, and gender-specific cancer risks, some families with a hereditary cancer predisposition syndrome may not meet these criteria. A negative family history of cancer does not rule out the possibility of a hereditary cancer syndrome.
1. Hereditary Breast Cancer
Breast cancer is the most common cancer that afflicts women in Singapore. Almost 25% of breast cancer patients have an underlying breast cancer predisposition syndrome.
Breast cancer genetic testing minimally includes over 20 breast cancer susceptibility genes. Clinically, the most important of these are the BRCA1 and BRCA2 genes. These are high-risk breast cancer genes, where carriers of pathogenic BRCA1/2 variants are predisposed to an increased risk of breast cancer (49–57% vs. general population risk of 12%) and ovarian cancer (18–40% vs. general population risk of 1%).
How to manage individuals at risk of hereditary breast cancer?Female carriers of a breast cancer susceptibility gene are recommended the following screening and surveillance measures to detect signs of cancer at the earliest and most treatable stage:
Treatment implicationsCancers that arise as a result of a germline predisposition are typically managed differently from those that arise sporadically. Patients may undergo more extensive local therapy if they are at an increased risk for metachronous malignancy. Studies have also identified BRCA1/2 status as clinically relevant in the selection of therapy for patients already diagnosed with breast cancer. Emerging breast and ovarian cancer research indicates that BRCA1/2 status predicts responsiveness to platinum-based chemotherapy, as well as to inhibitors of poly (ADP-ribose) polymerase (PARP), owing to the ability of these interventions to inhibit DNA repair pathways.
BRCA1/2 germline testing thus has important and expanding roles in treatment planning for subsets of patients with breast cancer.
2. Hereditary Colorectal Cancer
Colorectal cancer is the most common cancer observed in Singaporean men. Approximately 5–10% of cases are caused by a hereditary cancer predisposition syndrome.
Colorectal cancer genetic testing minimally includes over 19 colorectal cancer susceptibility genes. Clinically, the most important of these are the genes that cause familial adenomatous polyposis (APC) and Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM). Patients with familial adenomatous polyposis have a lifetime risk of colorectal cancer above 90%, while patients with Lynch syndrome are predisposed to an increased risk of colorectal cancer (20–47% vs. general population risk of 13–17%) and endometrial cancer (10–36% vs. general population risk of 6.9%).
How to manage individuals at risk of hereditary colorectal cancer?Carriers of a colorectal cancer susceptibility gene are recommended the following measures to detect signs of cancer early:
Perhaps the most important application of genetic testing is in individual cancer risk assessment. For the at-risk individual, identification of pathogenic variants in cancer predisposition genes enables risk reduction via enhanced surveillance or risk-reducing surgery.
Knowing who is at high risk allows us to intensify screening, resulting in early cancer detection and overall cost savings (Figure 3). Correspondingly, unaffected family members can avoid the inconveniences and costs of unnecessary surveillance.
We believe that a GP-led model of surveillance for high-risk individuals poses a convenient and accessible platform for the strategies outlined above, increasing patient adherence. We support initiatives to promote multidisciplinary coordinated care, potentially through academic-community partnerships, as these are valuable opportunities to enhance care for our patients.
We welcome any interested GP partners to contact us at firstname.lastname@example.org or 6436 8000.
The CGS actively contributes to research on a national and international scale. We have multiple ongoing research studies to identify novel pathogenic gene variants that predispose individuals to cancer. We are also involved in health services research to understand the psychosocial impact of hereditary cancer syndromes and are exploring the use of outreach methods to improve accessibility for cancer genetics testing. Lastly, we are also interested in the design of novel drugs tailored for gene-directed targeted treatment of patients with metastatic cancer.
The team at CGS are strong advocates in raising awareness and providing education to both the public and healthcare professionals. We regularly conduct public outreach programmes to educate the public on hereditary cancers. This is often done in conjunction with our annual ‘Jeans for Genes’ campaign in April to raise awareness on hereditary cancers.
We contribute knowledge through various channels which include GP education forums, multidisciplinary tumour board meetings, clinical rotation training, as well as local and international workshops, conferences and lectures.
In addition to training international aspiring genetics professionals, we are actively involved in the training of medical students, doctors and nurses – where CGS is regarded as a regional and international centre for cancer genetics training.
Medical professionals are welcome to contact us at email@example.com or 6436 8000 if they are interested to partner with us, find out more about our educational and training opportunities, or refer a patient or family with a cancer predisposition syndrome to any of our research programmes.
Jeanette Yuen is a Genetic Counsellor at the National Cancer Centre Singapore. She received her Masters of Genetic Counselling from the University of Sydney, where she studied the use of internet-based platforms to facilitate population screening. She has a keen interest in hereditary cancer syndromes and related health services research to improve patient outcomes through genetic counselling and testing.
GPs who would like more information on this topic, please contact Ms Yuen at jeanette.yuen.x.y.@nccs.com.sg.
Dr Chiang Jianbang is an Associate Consultant in Medical Oncology, National Cancer Centre Singapore (NCCS). He completed his internal medicine residency at Singapore General Hospital and senior residency in medical oncology at NCCS. He works with a dedicated team of geneticists and genetic counsellors in the Cancer Genetics Service at NCCS. He hopes to empower patients, family members and healthcare professionals with cancer genetics knowledge to improve personal and public health. His interests are in cancer genetics and lymphoproliferative disorders.
GPs who would like more information on this topic, please contact Dr Chiang at firstname.lastname@example.org.
Associate Professor Joanne Ngeow is a Senior Consultant in Medical Oncology, National Cancer Centre Singapore (NCCS) and Associate Professor at Lee Kong Chian School of Medicine, Nanyang Technological University. She heads the NCCS Cancer Genetics Service with an academic interest in hereditary cancer syndromes and translational cancer genetics. Her current clinical and research focus revolves around understanding cancer predisposition by studying cancers clustered in families, young adults with cancers and patients with multiple or rare cancers.
GPs who would like more information on this topic, please contact Prof Ngeow at email@example.com.
GPs can call the SingHealth Duke-NUS Genomic Medicine Centre for appointments at the following hotlines:KK Women's and Children's Hospital: 6692 2984National Cancer Centre Singapore: 6436 8288
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