LWBK1006-03 LWW-Govindan-Review November 24, 2011 11:19
Chapter 3•Etiology of Cancer Part 1 45in tissue of origin are generally the cause of cancer initiation, in some cases
the genetic changes may occur in the stromal cells resulting in aberrant
stromal–parenchymal interactions, leading to carcinogenesis.Answer 3.8. The answer is A.
The ASCO guidelines state that screening for cancer susceptibility syn-
dromes is not warranted in the general population but is recommended
for individuals with a suspected familial syndrome. In addition, the guide-
lines recommend that the testing should be done if the results can be easily
interpreted and will influence the management of the individuals being
tested.Answer 3.9. The answer is A.
Rb1 protein is a central regulator of the cell cycle. It is a 105-kDa protein
that undergoes phosphorylation at specific points in the cell cycle. During
the G0 and G1 phases of the cell cycle, hypophosphorylated Rb1 protein
binds to E2F transcription factors. Cyclin D-CDK4 phosphorylates Rb1
protein when the cell cycle transitions to the S phase. Phosphorylated RB1
protein dissociates from the E2F transcription factors, which then allows
these factors to recruit and activate other cell-cycle genes.Answer 3.10. The answer is D.
HNPCC, originally known as Lynch syndrome, is the most common can-
cer susceptibility disease and is responsible for at least 2% to 3% of
total colon cancer cases in the United States. HNPCC can be caused by
a germ line mutation in one of five genes:MLH1, MSH2, MSH6, PMS1,
orPMS2.All five genes function in DNA mismatch repair, and so muta-
tions in these genes affect genomic integrity. HNPCC is inherited in an
autosomal-dominant fashion with a penetrance of approximately 90%.
Men are affected at a higher penetrance, with women being less affected
but at an additional risk of endometrial cancer.Answer 3.11. The answer is A.
HNPCC accounts for 2% to 3% of total colon cancer cases, and is
caused by a germ line mutation in one of six DNA mismatch repair genes:
MLH1, MSH2, MSH3, MSH6, PMS1,orPMS2.HNPCC is inherited in
an autosomal-dominant manner with a penetrance of about 90%. Males
are affected at a higher penetrance. Patients with HNPCC have increased
risk of stomach, ovary, small intestine, ureter, and kidney cancers. Patients
typically present with colon cancer at a younger average age than patients
with sporadic colon cancer. In contrast to other familial colon cancer syn-
dromes, patients with HNPCC rarely exhibit polyps, making early detec-
tion difficult. Family members of patients with HNPCC should undergo
annual screening colonoscopy starting at approximately age 20 years. In
addition, women should undergo yearly pelvic examinations and ultra-
sound.