Genetic Risk Assessment & Counseling Flashcards

A woman's brother has cystic fibrosis (autosomal recessive), and she is unaffected. Before any testing, what is her risk of being a carrier?

Answer: 2/3

Of the unaffected offspring of two carriers, two of three expected genotypes are carriers, giving a 2/3 risk.

A woman has a 1/2 prior risk of carrying an X-linked recessive condition and has two unaffected sons. What is her posterior carrier risk by Bayesian analysis?

Answer: 1/5

Joint carrier probability 1/8 divided by (1/8 + 1/2) equals 1/5.

A Caucasian individual (prior carrier risk about 1/25) tests negative on a CF panel with a 90% detection rate. What is the approximate residual carrier risk?

Answer: 1/241

(1/25 x 0.10) / [(1/25 x 0.10) + (24/25 x 1)] is about 1/241.

A variant has a relative risk of 2.0 for a disease with a 12% baseline lifetime risk. What is the approximate absolute lifetime risk for a variant carrier?

Answer: 24%

Multiplying the baseline risk by the relative risk gives about 24%.

Which lifetime breast cancer risk estimate generally triggers consideration of annual breast MRI screening in addition to mammography?

Answer: 20% or greater

ACS and NCCN guidelines recommend supplemental MRI when model-estimated lifetime risk is 20% or higher.

Which statement best defines penetrance?

Answer: The proportion of individuals with a genotype who show the associated phenotype

Penetrance is the proportion of individuals with a particular genotype who express the phenotype.

Which risk model estimates breast cancer risk using personal factors such as age, reproductive history and biopsies, but incorporates only limited family history?

Answer: Gail model

The Gail model relies on personal risk factors with minimal family history and is not suited to hereditary cancer families.