#AGBTPH – Imran Haque, Overcoming artificial selection to realize the potential of germ line cancer screening

@imranshaque – Counsyl

Selfie related deaths:  Indiscriminate killer – equal risk for men vs. women.  40% of related deaths occurred in india.  10% of those who sing in the car….   About on par with shark attack deaths.

Cancer genomics is about 30 years old.  RB1 (1986).  Today many genes are known to be implicated in cancer.  Many of the more recent ones are less penetrant.

You can now get a commercial NGS test for 39-42 genes – and it’s relatively cheap.  How to get it:  1: get cancer, or 2: related to those who had cancer.

Models is under strain.

Access to “free” genetic testing for cancer risk is gated by personal and family history.

Very complicated decision tree.  Personal history of Breast cancer (long list of tree)… or other cancers or many many other factors.  Why is this bad?  Requires a 3rd degree pedigree, which may be too complex for an appointment.  Only a small number of patients who qualify actually get test: 7%.

Counsyl – First Care. (Product)  Helps you do your pre-test consult before you go into the clinic.  Then, offer follow up with genetic counsellor.  Reports it back to physician for appropriate treatment.  Anecdotally doing very well and increasing the number of patients who qualify for free testing.

Some insurers require additional barriers to get testing.  Patients may also be required to do pre-testing.  This helps to bring genetic counselling into the picture, and guarantees that the right tests are being used.

Counsyl can evaluate that – A large segment of population cancels the test if the requirements of pre-counselling are put in place.  Pre-test counselling is not being seen as a bonus.

Yield:

A good amount of cancers are driven by the same 2 genes (BRCA1/2).

Ability to integrate all high risk genes into single testes + discovery of new “moderate risk” genes has nearly doubled yield of diagnostic gremlin testing.  Expanded tests help, but still, total yields are around 7%.

Twin study, 1/3 of cancer risks come from genetics.  up to 55% from prostate cancer, but depends widely on the type of cancer.

Breast cancer: 20% heritability from single-gene penetrant alleles

Prostate Cancer: 55% heritability, but <5% from known single gene effects.

[Survey of literature, covering screening, risk and actionability.]

Equity:

Most genetic studies are done on non-diverse cohorts.  VUS rates differ systematically by ethnicity: BRCA1/2 ~3% for Europeans, ~7% for Africans and Asians. Similar for larger cancer panels.  Correlate to panel size as well, and systematic across other diagnostic panels.

Lack of diversity in discovery cohort leads to seriously skewed ability to process non European populations. Worse, possible misdiagnoses for non-white population.

Conclusions:

better systems to improve access;  better studies to demonstrate utility of bringing testing to wider population.

Polygenic risk is important and needs to be studied.

Issues of diversity are still plaguing us.  Need to include much more diverse populations.

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