Collaboration
Questions you wish that you could answer
(with the help of OHCRN)
Surveillance/Risk Reduction:
What proportion of individuals with pathogenic mutations in [moderate-penetrance gene] undergo [prophylactic risk‑reduction surgery]? (e.g., ATM/bilateral mastectomy)
What proportion of individuals with mutations of uncertain significance in [gene] undergo [prophylactic risk‑reduction surgery]? (e.g., BRCA1/bilateral mastectomy)
What is the uptake of [medication] for chemoprevention among individuals with [syndrome]? (e.g., aspirin/Lynch)
What proportion of individuals with mutations in [gene] undergo surveillance at the appropriate intervals? (e.g., BRCA1/mammo+MRI; TP53/whole body MRI)
Does early genetic diagnosis and surveillance modify age at cancer diagnosis? Does early genetic diagnosis and surveillance modify stage at cancer diagnosis?
Cancer Spectrum:
What proportion of individuals with mutations in [gene] have a [cancer diagnosis that has a tenuous association with the gene]? (e.g., PMS2/breast ca)
What is the age-specific cumulative incidence of [cancer] among carriers, stratified by uptake of risk-reducing surgery/adherence to surveillance/rural vs urban?
Among individuals with mutations in genes with emerging cancer associations (e.g., ATM and pancreatic cancer, CHEK2 and prostate cancer), what is the observed cancer incidence compared to the general population?
Clinical Trials and Prospective Studies:
Study of clonal hematopoiesis in BRCA1 carriers and its association with cancer, compared to age matched controls who have cancer.
Trial of high-dose aspirin on Lynch syndrome patients between ages 30-60 who do not have coronary artery disease.
Study of the effectiveness of [screening] vs [prophylactic surgery] in [gene positive] patients (e.g., endoscopy vs gastrectomy in CDH1 or endometrial biopsy vs hysterectomy in Lynch patients).
Study of a [novel screening blood test] in individuals with [syndrome] who have never been diagnosed with cancer.
Gene Discovery:
I would like to validate a PRS on gene positive and negative people to stratify cancer risk.
Health System:
What is the difference in healthcare costs for BRCA1 carriers who undergo risk‑reduction surgeries compared to those who undergo cancer treatment?
What is the difference in healthcare cost for [gene positive] individuals who undergo regular surveillance compared to those who undergo cancer treatment?
Compare [hereditary cancer syndrome] carriers managed in multidisciplinary institutions vs those in community care. Is there a difference in outcomes?
Genetic Counselling:
What is the hazard of incident cancer after genetic result disclosure?
How are different laboratories reporting certain variants (e.g. APC I1307K; CHEK2 I157T). Is management altered based on classification?
What are the attitudes of patients who have had their germline mutations reclassified?
What proportion of individuals with mutations suspicious for being of germline origin identified on tumor genomic profiling undergo confirmatory germline testing?
