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An Autosome-Wide Scan for Linkage Disequilibrium–Based Association in Sporadic Breast Cancer Cases in Eastern Finland: Three Candidate Regions Found

Departments of ¹ Pathology and Forensic Medicine, ² Neuroscience and Neurology, and ³ Clinical Nutrition, University of Kuopio; Departments of ⁴ Oncology and ⁵ Surgery, Kuopio University Hospital, Kuopio, Finland; ⁶ Cancer Research UK Human Cancer Genetics Research Group, Department of Oncology, and ⁷ Cancer Research UK Genetic Epidemiology Unit, Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom; ⁸ Fujitsu, Fujitsu, Finland; ⁹ Department of Pathology, Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland; and ¹⁰ Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland

Requests for reprints: Jaana M. Hartikainen, Department of Pathology and Forensic Medicine, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland. Phone: 358-17-162754; Fax: 358-17-162753. E-mail: jaana{at}hartikainen@uku.fi

Breast cancer is the most common of cancers among women in industrialized countries. Many of breast cancer risk factors are known, but the majority of the genetic background is still unknown. Linkage disequilibrium–based association is a powerful tool for mapping disease genes and is suitable for mapping complex traits in founder populations. We report the results of a two-stage, autosome-wide scan for LD with breast cancer. Our aim was to identify genetic risk factors for sporadic breast cancer in an eastern Finnish population. Our case-control set is from the province of northern Savo in the late-settlement area of eastern Finland. This population is relatively young and genetically homogeneous. We used 435 autosomal microsatellite markers spaced by an average of 10 cM in a set of 49 breast cancer cases and 50 controls. In the first-stage scan, we found 21 markers in LD with breast cancer (Ps = 0.003-0.046, Fisher's exact test). In the second-stage scan with markers flanking 21 positive loci, four significant markers were found (Ps = 0.013-0.046, Fisher's exact test). Haplotype analysis using global score method with two, three, or four markers also revealed four positive marker combinations (simulated P for global score = 0.003-0.021). Our results suggest breast cancer–associated regions on 3p26, 11q23, and 22q13.1 in an eastern Finnish population.

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