PB#147: Lynch Syndrome

Question 1

Percentage of cases of uterine cancer attributable to a hereditary causes; percentage of cases of ovarian cancer attributable to a hereditary cause

Answer 1

~3-5%; 8-13%

Question 2

Syndrome that accounts for most cases of hereditary uterine and CR cancer

Answer 2

Lynch syndrome

Question 3

Top two most common causes of inherited ovarian cancer (in order)

Answer 3

1) Hereditary breast and ovarian cancer syndrome
2) Lynch syndrome

Question 4

Inheritance pattern of Lynch syndrome

Answer 4

Highly penetrant AD condition

Question 5

General molecular defect caused by Lynch syndrome

Answer 5

Defects in DNA MMR

Question 6

Population prevalence of Lynch syndrome

Answer 6

~1 in 600-3,000 individuals

Question 7

Most common genes associated w/ Lynch syndrome (4)

Answer 7

MLH1, MSH2, MSH6, PMS2

Question 8

Gene that, when deletions present, may also lead to inactivation of MSH2 and result in Lynch syndrome

Answer 8

EpCAM

Question 9

Incidence of Lynch syndrome in pts presenting w/ endometrial cancer

Answer 9

~2.3%

Question 10

Incidence of Lynch syndrome in pts presenting w/ CR cancer

Answer 10

~2.2%

Question 11

Clinical feature of Lynch syndrome endometrial/CR cancers

Answer 11

Substantially greater portion of early-onset cancers

Question 12

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

Answer 12

At least 5-9%; 5-7%

Question 13

Risk of CR cancer through 70 y/o for pts w/ Lynch syndrome; risk of CR cancer through 70 y/o in general population

Answer 13

18-61%; 1.7%

Question 14

Risk of endometrial cancer through 70 y/o for pts w/ Lynch syndrome

Answer 14

16-61% (equaling or exceeding risk of CR cancer)

Question 15

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

Answer 15

5-10%; ~1%; 38-46%; 12-20%

Question 16

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;

Answer 16

20-54%; 21-49%; 16-61%

Question 17

Noteworthy clinical feature of endometrial cancer among MSH6 mutation carriers

Answer 17

Later average age of disease onset

Question 18

Is gyn cancer or GI cancer the more common presenting cancer among pts w/ documented Lynch syndrome and metachronous GI and gyn malignancies?

Answer 18

Gyn cancer (in >50% of cases)

Question 19

Median interval between dx of endometrial cancer and dx of CR cancer among Lynch syndrome pts w/ metachronous GI and gyn malignancies

Answer 19

11 years

Question 20

Mean age of onset of endometrial cancer among pts w/ Lynch syndrome

Answer 20

47-49 y/o

Question 21

Histological feature more common w/ Lynch-associated endometrial cancer

Answer 21

Nonendometrioid histology

Question 22

Percentage of pts w/ Lynch syndrome who have endometrial path characteristics w/ that warrant adjuvant therapy s/p hyst

Answer 22

~25% (despite earlier disease stage at dx)

Question 23

Mean age of dx of ovarian cancer in Lynch syndrome pts

Answer 23

42-49 y/o

Question 24

Disease stage seen w/ Lynch syndrome pts at dx compared to pts w/ sporadic ovarian cancer

Answer 24

Earlier disease stage

Question 25

Overrepresented histologies seen w/ Lynch-associated ovarian cancer compared to sporadic ovarian cancer (2)

Answer 25

Endometrioid, clear cell

Question 26

Is 5-year survival rate higher in Lynch-associated ovarian cancer or sporadic ovarian cancer?

Answer 26

Not statistically different