الفهرس 
GENETIC BASIS OF COLORECTAL CANCEROnly 14 pages are availabe for public view
 |  | from | 128 |  |  |
| | | from | 128 | | |
Abstract
HNPCC is an autosomal dominant trait. It has an incidence of 1:1.000 in the general population and up to 1:100 in individuals with CRC, which accounts for 3-8% of CRCs.
It was first described in 1913 by Aldred Warthin, in the family of his seamstress (later known as ”family G”). This hereditary pattern of cancers gained little attention over the subsequent 50 years or more, until characterized by Henry Lynch as the Cancer Family Syndrome (CFS). The term CFS was subsequently replaced by the term ”Lynch Syndrome” which is preferred than HNPCC to include both colorectal and extracolonic cancers.
Based on a series of international collaborative studies, they developed the ”Amsterdam criteria” to standardize diagnostic criteria of HNPCC, which later on modified by the national cancer institute workshop as ”Bethesda guidelines”.
There are genetic mutations responsible for developing of HNPCC. These mutations occur in any one of five DNA genes. The majority of mutations responsible for HNPCC occur in two genes, MSH2 and MLH1. The protein products of these genes are responsible for repair of mutations that occur in other genes. These genes known as mismatch repair genes ”MMR”.
HNPCC is characterized by an 80% lifetime risk for CRC and a 60% lifetime risk for endometrial cancer with onset at a young age (median of 44 years), so discovering of susceptible groups by family history, continuous screening, and detection of germ-line mutations in DNA MMR genes are important in HNPCC management.
Prophylactic total abdominal colectomy with ileorectal anastomosis(TAC-IR) is strongly considered for diagnosed HNPCC member with close regular follow up, as there is a 1% annual risk for cancer in the remaining rectum.
Prophylactic total abdominal hysterectomy–bilateral salpingo–oophorectomy (TAH–BSO) may be considered for women who have mutation-proven HNPCC.
Adjuvant 5-FU- based chemotherapy after surgery will improve prognosis especially for patient with MSI+ tumors.
HNPCC colorectal cancers are associated with a better prognosis compared to sporadic CRCs.