Devita, Hellman, and Rosenberg's Cancer

LWBK1006-20 LWW-Govindan-Review December 12, 2011 19:4

Chapter 20•Cancer of the Gastrointestinal Tract 275

members who do not carry the known mutation, there is no need for inten-

sive surveillance, and routine colorectal screening according to national

guidelines is recommended. For family members who carry the germ line

MMR mutation, the National Comprehensive Cancer Network recom-

mends colonoscopies every 1 to 2 years beginning at age 20 to 25 years

or 5 to 10 years younger than the earliest age of diagnosis in the family,

whichever comes first. For women with the MMR mutation, screening

for endometrial cancer with transvaginal ultrasound with or without CA

125 for ovarian cancer screening is recommended by age 30 to 35 years.

Women who have completed childbearing could opt for prophylactic hys-

terectomy and bilateral salpingo-oophorectomy to reduce their risks for

developing endometrial and ovarian cancers.

Answer 20.5.5. The answer is D.

Germ line mutations in the MMR genes MSH2, MLH1, and MSH6

account for 90% of all patients with HNPCC. APC gene mutation is com-

monly associated with FAP. MYH-associated polyposis is a rare inherited

syndrome with increased for colorectal cancer.

Answer 20.5.6. The answer is D.

The standard adjuvant therapy for patients with stage III colon cancer is

oxaliplatin with 5FU based on the MOSAIC and the NSABP-C07 studies.

Recent updates of the MOSAIC study demonstrated a significant improve-

ment in 6-year overall survival among patients with stage III colorectal

cancer treated with FOLFOX compared with those treated with infusional

5FU/LV. Irinotecan-based regimens are not recommended for adjuvant

therapy for patients with stage III according to the negative results of

three large randomized studies. Current studies on adding bevacizumab

and cetuximab to oxaliplatin regimens are ongoing.

Answer 20.5.7. The answer is C.

More than 80% of the administered dose of 5FU is eliminated via the dihy-

dropyrimidine dehydrogenase (DPD) enzyme. Patients with DPD defi-

ciency are at high risk for 5FU toxicities, such as severe neutropenia, neu-

tropenic fever, diarrhea, mucositis, cerebellar ataxia, neurotoxicity, and

even death. The most common mutation associated with DPD deficiency

is the IVS14+1G>A, DPYD*2A mutation. Complete DPD deficiency

has been reported in patients homozygous for this allele, whereas par-

tial DPD deficiency occurs in patients heterozygous for this allele. More

than 40 other mutations and polymorphism have been identified in the

DPD gene, although the functional significance of these polymorphisms

is not clear. Moreover, instances of low DPD activity have been reported

in patients without any identified DPD mutation or polymorphism. The

TSER *3/*3 genotype is associated with higher levels of thymidine

synthase and lower tumor response to 5FU therapy. Although it is

possible that this patient is homozygous for the UGT1A1∗28 gene

resulting in severe neutropenia and diarrhea, the constellation of the

patient’s symptoms, including cerebellar ataxia and mucositis, is more