Genetic Counseling for Cancer Flashcards
What are the types of hereditary cancer genes?
oncogenes (RET, MET): normally encourage cell growth, when mutated, flood cells with signals to divide, “gain of function”
Tumor suppressor genes (BRCA1/2, APC, TP53): restrain cell growth, when missing or inactivated, cells grow and divide uncontrolablly, “loss of function”
Mismatch repair genes (MLH1, MSH2, MSH6, PMS2): when mutated, fail to correct DNA replication errors, allowing mutations to accumulate in regulatory genes
What are the features of an inherited predisposition?
younger age of onset (one somatic mutation is acquired in less time than two)
multiple primary cancers (multiple cells may acquire a second somatic mutation)
What is the relationship between cancer and genetics?
approximately 5-10% of cancer is caused by an inherited predisposition (certain cancer, like ovarian, are more likely to be hereditary)
most cancer syndromes are NOT 100% penetrant
What genes and components are associated with HBOC?
BRCA1/2
breast, ovarian, prostate, pancreatic
What genes and components are associated with Cowden?
PTEN
breast, endometrial, thyroid
What genes and components are associated with Peutz-Jeghers?
STK11/LKB1
GI, breast, gonadal, endometrial
What genes and components are associated with Li-Fraumeni syndrome?
TP53
breast, sarcoma, acute leukemia, adrenocortical carcinoma, brain tumors
What genes and components are associated with HNPCC (Lynch)?
MLH1, MSH2, MSH6, PMS2, EPCAM
colon, small bowel, endometrial, stomach, ovarian, GU
What genes and components are associated with FAP, MAP?
APC, MUTYH
FAP: colon, small bowel, stomach, pancreas, thyroid, CNS, liver, bile duct
What are the reasons to refer to cancer genetics?
personal history of cancer (early onset, multiple primary/multifocal/bilateral, rare cancers, suggestive non-malignant features, signature pathology findings in a patient's tumor, member of a population at risk, unusual degree of cancer anxiety) family history (multiple individuals in the same generations of individuals affected with related cancers, multiple individuals in the same generation affected with related cancers, early onset, multiple primary cancers/bilateral, rare cancers, relative with known mutation)
Where do we get referrals for cancer genetics from?
physicians (primary care, OBGYN, oncologist, surgeon, other)
self-referred
unintended/incidental findings (WES/WGS, carrier screening, direct to consumer testing)
What is the agenda for cancer counseling sessions?
pre-visit preparation
initial consultation (contracting, family and medical history, risk assessment, discussion of cancer genetics, explanation of testing, implications for medical management)
results disclosure
How do you prepare for a cancer counseling visit?
initial contact with the patient to ascertain reason for referral
assess appropriateness of referral and eligibility for ongoing research studies
logistics (outline the process of genetic counseling and testing, give patient homework as necessary, schedule appointment, discuss insurance considerations)
What are the key points to a cancer pedigree?
at least three generations
who’s been diagnosed with cancer? (what type of cancer, primary site of cancer, age at diagnosis, pathology markers)
polyp burden
age of risk-reducing surgery
contribution of major environmental risk factors
What could make a family history uninformative?
patient is adopted and has no info about biological family
small family size
patient has no information regarding family members or cancer history
key family members died young
key family members had surgeries that obscure risk
sex effect (there is a paucity of females in the family on either side)
patient is young and so are their parents and siblings
erroneous information (often give metastatic sites rather than primary location, can confuse any cancer in the abdominal region)
incomplete penetrance
mosaicism (rare)
inaccurate or missing information
