title: A specific haplotype of single nucleotide polymorphisms on chromosome 19q13.2-3 encompassing the gene RAI is indicative of post-menopausal breast cancer before age 55.
abstract: The new genetic information, in particular the greatly increased density of markers in the chromosomal maps, may permit analysis of the importance of genes in the development of disease exclusively from molecular epidemiological studies. Motivated by our previous results on the same region in relation to basal cell carcinoma we have investigated the occurrence of post-menopausal breast cancer in relation to a number of single nucleotide polymorphisms in the chromosomal region 19q13.2-3. A case-control study including 425 human cases and a similar number of controls was nested in a population-based prospective investigation encompassing 24 697 Danish post-menopausal women (aged 50-64 at inclusion) living in Copenhagen or Aarhus. We combined three markers located together in or near the gene RAI into a high-risk haplotype. Compared with all other haplotypes, those who were homozygous had a rate ratio of 1.64 (95% CI 1.17-2.29, P < or = 0.004) for development of breast cancer. When we further focused on those persons with post-menopausal breast cancer before age 55 the rate ratio increased to 9.5 (95% CI 2.21-40.79, P < or = 0.003). The likely explanation for our results is a common recessive genetic variant located in or near the gene RAI, which, when homozygous, conveys an increased risk of breast cancer. Presumably it is identical to the genetic variant previously observed in the same region that increases the risk of basal cell carcinoma before age 50.
authors.affiliation: Institute of Human Genetics, The Bartholin Building, University of Aarhus, Denmark. nexo@humgen.au.dk
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Nexø
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Tina
authors.initials: T
authors.lastname: Ketelsen
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Bukowy
authors.forename: Birthe L
authors.initials: BL
authors.lastname: Thomsen
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
mesh_terms: D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns / Q000235:genetics; D018895:Microsatellite Repeats; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause; D011446:Prospective Studies; D012097:Repressor Proteins; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; D004247:DNA