PB#147: Lynch Syndrome Flashcards
Percentage of cases of uterine cancer attributable to a hereditary causes; percentage of cases of ovarian cancer attributable to a hereditary cause
~3-5%; 8-13%
Syndrome that accounts for most cases of hereditary uterine and CR cancer
Lynch syndrome
Top two most common causes of inherited ovarian cancer (in order)
1) Hereditary breast and ovarian cancer syndrome
2) Lynch syndrome
Inheritance pattern of Lynch syndrome
Highly penetrant AD condition
General molecular defect caused by Lynch syndrome
Defects in DNA MMR
Population prevalence of Lynch syndrome
~1 in 600-3,000 individuals
Most common genes associated w/ Lynch syndrome (4)
MLH1, MSH2, MSH6, PMS2
Gene that, when deletions present, may also lead to inactivation of MSH2 and result in Lynch syndrome
EpCAM
Incidence of Lynch syndrome in pts presenting w/ endometrial cancer
~2.3%
Incidence of Lynch syndrome in pts presenting w/ CR cancer
~2.2%
Clinical feature of Lynch syndrome endometrial/CR cancers
Substantially greater portion of early-onset cancers
Percentage of pts <50 y/o w/ endometrial cancer who will have a detectable deleterious MMR gene mutation associated w/ Lynch syndrome; percentage of pts <50 y/o w/ CR cancer who will have a detectable deleterious MMR gene mutation associated w/ Lynch syndrome
At least 5-9%; 5-7%
Risk of CR cancer through 70 y/o for pts w/ Lynch syndrome; risk of CR cancer through 70 y/o in general population
18-61%; 1.7%
Risk of endometrial cancer through 70 y/o for pts w/ Lynch syndrome
16-61% (equaling or exceeding risk of CR cancer)
Risk of ovarian cancer through 70 y/o for pts w/ Lynch syndrome; risk of ovarian cancer through 70 y/o in general population; risk of ovarian cancer through 70 y/o for pts w/ BRCA1 mutation; risk of ovarian cancer through 70 y/o for pts w/ BRCA2 mutation
5-10%; ~1%; 38-46%; 12-20%
Risk of endometrial cancer by 70 y/o among MLH1 mutation carriers; risk of endometrial cancer by 70 y/o among MSH2 mutation carriers; risk of endometrial cancer by 70 y/o among MSH6 mutation carriers;
20-54%; 21-49%; 16-61%
Noteworthy clinical feature of endometrial cancer among MSH6 mutation carriers
Later average age of disease onset
Is gyn cancer or GI cancer the more common presenting cancer among pts w/ documented Lynch syndrome and metachronous GI and gyn malignancies?
Gyn cancer (in >50% of cases)
Median interval between dx of endometrial cancer and dx of CR cancer among Lynch syndrome pts w/ metachronous GI and gyn malignancies
11 years
Mean age of onset of endometrial cancer among pts w/ Lynch syndrome
47-49 y/o
Histological feature more common w/ Lynch-associated endometrial cancer
Nonendometrioid histology
Percentage of pts w/ Lynch syndrome who have endometrial path characteristics w/ that warrant adjuvant therapy s/p hyst
~25% (despite earlier disease stage at dx)
Mean age of dx of ovarian cancer in Lynch syndrome pts
42-49 y/o
Disease stage seen w/ Lynch syndrome pts at dx compared to pts w/ sporadic ovarian cancer
Earlier disease stage