Detection of BRCA1 and BRCA2 mutations in a selected Hawaii population.

Objective: To examine BRCA1 and BRCA2 gene sequence testing results, specifically variants of uncertain clinical significance in the BRCA1 and/or BRCA2 sequences of an ethnically diverse population within a particular time constraint.

Methods: A retrospective chart analysis of BRCA1 and BRCA2 gene sequence testing cases was reviewed at Kapiolani Medical Center for Women and Children from October 1996 to November 2007. Information was extracted and categorized regarding each patient's age, age of cancer onset, types of can cer in family history, ethnicity/ancestry, type of test used for analysis, and specific characteristics of each variant.

Results: Of the 273 patients who received BRCA1/BRCA2 gene sequence testing, 45 patients demonstrated variants of uncertain clinical significance. A total of 48 variants of uncertain clinical significance were reported and 9 of the variants had previously never been observed before. Of the 45 patients, 33.3% were Caucasian, 40% were Asian, and 26.67% were of mixed ethnicity.

Conclusions: Within the local population at Kapiolani Medical Center for Women and Children, a significantly higher proportion of patients exhibited variants compared to the national average. A high percentage of variants existed among the ethnically diverse as well as the Caucasian population. Gene sequence testing is a valuable asset for physicians treating patients who are at risk for inherited cancer: however, the direction of treatment remains clinically questionable for patients with variants of unknown significance.