In new recommendations published in the Journal of Clinical Oncology, ASCO stated that family history of cancer in first- and second-degree relatives is critical to assessing for familial risk in patients with cancer. ASCO’s recommendations are the first to focus on family history taking specifically in oncology to help determine patients’ personal genetic risk for cancer.
Although the current standard in medical genetics, genetic counseling and research settings is a comprehensive recording of three generations, following a review of all available evidence, ASCO concluded that reported family history is most accurate in close relatives and loses accuracy in more distant relatives.
“Genetic factors are a key component of precision medicine because they can unlock important information that can help an oncologist determine the best course of individualized treatment, “ said ASCO President Clifford A. Hudis, MD, FACP. “An adequate family history is key to identifying those patients whose cancer may be associated with inherited genetic factors.”
For each relative with cancer, ASCO recommends recording type of primary cancer(s), age at diagnosis, lineage (maternal and/or paternal), ethnicity and results of any cancer genetic testing in any relative. Family history information should be recorded at a patient’s initial visit to the oncology provider, and be reassessed if new information about family members diagnosed with cancer becomes available.
Addressing Barriers to Implementation
In a separate analysis of data from ASCO’s Quality Oncology Practice Initiative QOPI®, results showed that of breast and colorectal patients with a first degree family history of cancer, 79.8 percent were documented in their chart and for those with a second degree family history of cancer, 64.6 percent were documented. These results document a greater opportunity for oncologists to maximize the potential of family history taking, and set a baseline for further quality improvement efforts.
To address barriers to implementation, ASCO recommends increasing patient education and awareness on the importance of a family history and the significance of a cancer risk assessment for patients and their family. Cancer.Net, ASCO’s patient website, will offer an article and infographic, as well as a cancer family questionnaire patients can download.
ASCO also notes that the increasing use of electronic health records (EHRs) can help providers overcome challenges to adopting these new recommendations.
ASCO will be providing a comprehensive update of cancer genetics including family history assessment at its annual meeting. For more information about ASCO’s prevention and genetics work, please click here.
Our new study shows that we can do much more to identify patients with Lynch syndrome in the UK. We already know that diagnosing Lynch syndrome can affect the treatment of a patient with bowel cancer – and can save the lives of their family members. Every team dealing with bowel cancer patients needs to routinely discuss the possibility of an inherited cancer syndrome. This study has just been published in the journal ‘Frontline Gastroenterology’.
Lynch syndrome is the most common familial bowel cancer syndrome. European guidelines suggest selective screening of appropriate colorectal cancer patients, according to the revised Bethesda criteria. Many eligible patients do not undergo the necessary investigation.
What this study adds
This is the first time that UK practice in this area has been evaluated. Our patients are assessed haphazardly for Lynch syndrome, and we do not follow international guidance. This will lead to under-diagnosis and missed opportunities to reduce cancer mortality. impact on clinical practice in the foreseeable
Colorectal cancer teams should incorporate a revised Bethesda assessment into the routine discussion of each new patient. They should develop screening and referral pathways with their local genetics services. This aspect of their work can be audited and may become a quality standard in the future.
The “Family History of Bowel Cancer” clinic at the West Middlesex University Hospital, led by Dr Kevin Monahan, helps assess patients with a significant family background of cancers. Patients, GPs and other health professionals can read more about our service, and how to make a referral, at https://familyhistorybowelcancer.wordpress.com.
Article: UK colorectal cancer patients are inadequately assessed for Lynch syndrome. Maria Adelson, Samuel Pannick, James E East, Peter Risby, Peter Dawson, Kevin J Monahan
This information sheet is available in pdf form by clicking this link Variants of Uncertain Significance
Lynch Syndrome is a genetic condition that carries a high risk of colorectal (bowel) cancer and other cancers. Individuals at risk for Lynch Syndrome can have genetic testing for it. The test may confirm a diagnosis and determine actions that can be taken. Results from genetic testing can also affect the perspectives of relatives who might also be affected.
What is a VUS? A variant of uncertain significance (VUS) is a genetic sequence change whose association with disease risk is currently unknown.
Most genetic test results are either ‘positive for a deleterious mutation,’ or ‘no mutation detected.’ However, as in many areas of medicine, results are occasionally inconclusive; consequently, medical management decisions are based on other contributing factors.
In the field of cancer genetics, clinicians and patients have encountered challenges related to the significance of unclassified genetic variants (UV) or variants of unknown significance (VUS). VUS are data that may not provide enough information to make decisions. As the field of medical genetics moves toward whole genome sequencing (WGS), these challenges will inevitably become more frequent. VUS represent ambiguous and uncertain data, for which pathogenicity has not been demonstrated or excluded in published literature, mutation databases or on the basis of other clinical findings. Such variants present a clinical interpretation challenge and also evoke new counseling dilemmas for the understanding and psychosocial impact of uncertain genetic test results.
How do I manage a patient with a VUS? Since it is not possible to classify the genetic change as deleterious or benign, the patient should be managed based on personal and family history.
Individualized management may include increased surveillance and possibly other interventions, such as surgery or chemoprevention. Consider reviewing the case with your specialist to discuss appropriate management in the context of the specific patient and family history, and to explore whether additional work-up is indicated for the patient or family.
In practice, patients may be screened as usual for Lynch Syndrome if the clinical history was suggestive of this, but we would currently be unable to offer presymptomatic genetics testing to unaffected relatives, unless the variant was reclassified as a probable pathogenic mutation.
|| No mutation detected (about 90% of results)
|| Variant, favor polymorphism (rare)
|| Genetic Variant of Uncertain Significance (rare)
|| Variant, suspected deleterious (rare)
|| Almost certainly negative
|| Almost certainly positive
| Cause of cancer in family has not been determined; patient may have increased cancer risk, but hereditary cancer less likely
|| Cause of cancer in family not likely due to this variant; patient may have increased cancer risk, but hereditary cancer less likely
|| May turn out to be positive or negative; physician will be notified once reclassified
|| Patient likely has the syndrome with cancer risks defined by the syndrome
|| Patient is confirmed to have the syndrome; cancer risks defined by the syndrome
| Manage based on personal and family history
|| Manage based on personal and family history
|| Manage based on personal and family history; provider should receive invitation for patient to participate in Variant Classification Program
|| Manage according to guidelines for syndrome; suggest single site testing for family members
|| Manage according to guidelines for syndrome; suggest single site testing for family members
|What happens once a variant is reclassified?
Over time, a variant will often get reclassified as either a benign polymorphism or a deleterious mutation. When this occurs, an amended report is sent to the original ordering provider. While most clinical genetics centres proactively reclassify variants and communicates new findings to the original ordering providers, it is important to urge your patients with VUSs to keep in contact with your office or to notify the laboratory of an alternative provider if they move, so that they and their family can benefit from new information as it becomes available.
Cancer Research UK (Photo credit: Wikipedia)
A UK trial is investigating whether a curry ingredient can improve the treatment of patients with advanced bowel cancer.
Scientists will supplement standard chemotherapy with pills containing curcumin, a compound found in the yellow curry spice turmeric.
Laboratory tests have suggested that curcumin can boost the ability of chemotherapy drugs to kill bowel cancer cells. The compound is known to have powerful anti-inflammatory properties and also acts as an antioxidant.
Turmeric powder 薑黃粉 (Photo credit: Wikipedia)
Some studies have indicated it may slow the spread of cancer, improve the effectiveness of chemotherapy and protect healthy cells from the effects of radiotherapy. However, hard evidence from properly conducted scientific trials is lacking.
The two-year trial, by scientists from Cancer Research UK and the University of Leicester, aims to recruit about 40 patients with bowel cancer that has spread to the liver.
Trial leader Professor William Steward, director of the Experimental Cancer Medicine Centre at the University of Leicester, said: “The prospect that curcumin might increase the sensitivity of cancer cells to chemotherapy is exciting because it could mean giving lower doses, so patients have fewer side-effects and can keep having treatment for longer.”
Read more here
What is your family history?
The Family History of Bowel Cancer Registry was founded in 2010. It has been a useful resource for hereditary and non-hereditary colorectal cancer research conducted at West Middlesex University Hospital. Our clinicians and researchers have utilised the information our registry provides for research on the causes of colorectal cancer. It helps to link our patients with their screening and surveillance programmes, and also in to local and national research projects such as the Cancer Research UK study CORGI (COloRectal Gene Identification Study). The registry also provides services to families, community health professionals, and the general public, including educational materials and programs on hereditary colorectal cancer syndromes, cancer genetics, and current research.
Family History of Bowel Cancer Registry;
- Evaluation of family histories based on questionnaires and medical records
- Genetic counseling
- Recommendations regarding cancer management
- Development and implementation of research studies
- Provide information for patients and professionals about cancer genetics research
- Referral of patients and service providers to community and hospital resources
- Development of literature for use by public and private agencies and individual patients and their families
Conditions and Syndromes;
- Family History of Cancer
- Lynch Syndrome
- Familial colorectal cancer syndrome-X
- Familial adenomatous polyposis coli (FAP)
- MUTYH-associated polyposis (MAP)
- Peutz-Jeghers syndrome (PJS)
- Juvenile polyposis
- Hyperplastic polyposis syndrome (HPS)
- Hereditary mixed polyposis syndrome (HMPS)
- PTEN-mutation spectrum