The identification of Lynch syndrome in British Columbia.
OBJECTIVE
To determine the prevalence of Lynch syndrome mutations in a Canadian hereditary cancer clinic population, and to determine the effectiveness of the program's referral criteria and testing algorithm.


METHODS
A retrospective chart review of all patients who were referred for and received genetic counselling at the BC Cancer Agency's Hereditary Cancer Program for a family history of colon cancer from August 1, 2004, to September 1, 2006, was performed. Charts were reviewed for referral criteria met, cancer history, whether testing was offered and the outcome of testing.


RESULTS
Lynch syndrome was confirmed or highly suspected in 14.3% of index test patients (eight of 56) by the identification of a deleterious mutation or variant likely to be deleterious in either of the hMLH1 or hMSH2 mismatch repair genes. In the program, the two most effective criteria were a personal diagnosis of two or more primary Lynch syndrome-related cancers (one diagnosed at younger than 50 years of age) or two first-degree relatives with a Lynch syndrome-related cancer (both diagnosed at younger than 50 years of age). The respective positive predictive values of these two criteria were calculated to be 66.7% (95% CI 40% to 93%) and 58.3% (95% CI 30.4% to 86.2%).


CONCLUSIONS
The Hereditary Cancer Program developed and successfully implemented an approach that selected individuals at risk for Lynch syndrome with a significant pretest probability of mutation of 14.3%. Improved ascertainment of families with Lynch syndrome will require greater physician awareness of referral criteria, program advances in the testing algorithm and a population-based approach to screening incident colon cancers.
Cremin
Carol M
CM
Hereditary Cancer Program, BC Cancer Agency, Vancouver, Canada. ccremin@bccancer.bc.ca
Armstrong
Linlea
L
Gill
Sharlene
S
Huntsman
David
D
Bajdik
Chris
C
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D020137:Base Pair Mismatch; D001955:British Columbia / Q000453:epidemiology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods / Q000592:standards; D005260:Female; D005817:Genetic Counseling / Q000379:methods / Q000592:standards; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008487:Medical History Taking / Q000379:methods / Q000592:standards; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015995:Prevalence; D015397:Program Evaluation
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein