Abstract Background: In an ethnically-homogeneous population, it is valuable to identify founder mutations in cancer-predisposing genes. Founder mutations have been found in four breast cancer predisposing genes in French-Canadian breast cancer families. The frequencies of the mutant alleles have not been measured in a large series of unselected breast cancer patients from Quebec, nor in healthy controls. These estimates are necessary to measure their contribution to the hereditary burden of breast cancer in Quebec and to help develop genetic screening policies which are appropriate for the province.Methods: We studied 564 French-Canadian women with early-onset invasive breast cancer who were treated at a single Montreal hospital. Patients had been diagnosed at age 50 or less, and were ascertained between 2004 and 2008. We screened all 564 patients for nine founder mutations; four in BRCA1, three in BRCA2 and one each in PALB2 and CHEK2. We also studied 6433 DNA samples from newborn infants from the Quebec City area to estimate the frequency of the nine variant alleles in the French-Canadian population.Results: We identified a mutation in 36 of the 564 breast cancer cases (6.4%) and in 35 of 6443 controls (0.5%). In the breast cancer patients, the majority of mutations were in BRCA2 (54%). However, in the general population (newborn infants), the majority of mutations were in CHEK2 (54%). The odds ratio for breast cancer to age 50, given a BRCA1 mutation was 10.1 (95% CI: 3.7 to 28) and given a BRCA2 mutation was 29.5 (95% CI: 12.9 – 67). The odds ratio for breast cancer to age 50, given a CHEK2 mutation was 3.6 (95% CI: 1.4 – 9.1). One-half of the women with a mutation had a first or second-degree relative diagnosed with breast or ovarian cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 902.