RT Journal Article
SR Electronic
T1 Gynecological tumors revealing hereditary nonpolyposis colorectal cancer: analysis of a large Lebanese pedigree
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 1516
OP 1521
DO 10.1136/ijgc-00009577-200607000-00004
VO 16
IS 4
A1 R. Akoum
A1 A. Ghaoui
A1 E. Brihi
A1 M. Ghabash
A1 J Abou Atme
YR 2006
UL http://ijgc.bmj.com/content/16/4/1516.abstract
AB The objective of this study was to evaluate the aggregation of colorectal cancer (CRC) and hereditary nonpolyposis colorectal cancer (HNPCC)–related extracolonic cancers in an extended Lebanese family with HNPCC. This was a pedigree analysis and a prospective follow-up over an 8-year period. The causative germ line mutation was detected using denaturing high-performance liquid chromatography, polymerase chain reaction (PCR) of short fluorescent fragments, and direct DNA sequencing of purified PCR products. The penetrance of CRC is high and accounts for approximately two thirds of risk carriers with an early age of onset (21 years). The extracolonic cancer spectrum includes ovary, endometrium, small bowel, skin, and brain, with an age of onset as early as 30 years. The causative mismatch repair gene mutation is an MSH2 point mutation involving the splice donor site of intron 3 (G→A). Scrutinized in genomic DNA from 35 consented members, it was found in 18 of them and cosegregates with the cancer phenotype in the family. Early-onset ovarian and endometrial carcinomas may reveal HNPCC families in the Middle Eastern region, with MSH2 germ line mutation. We propose a biannual screening program, starting around the age of 20–25 years, pending additional data on this topic.