title: Recurrent HOXB13 mutations in the Dutch population do not associate with increased breast cancer risk.
abstract: The HOXB13 p.G84E mutation has been firmly established as a prostate cancer susceptibility allele. Although HOXB13 also plays a role in breast tumor progression, the association of HOXB13 p.G84E with breast cancer risk is less evident. Therefore, we comprehensively interrogated the entire HOXB13 coding sequence for mutations in 1,250 non-BRCA1/2 familial breast cancer cases and 800 controls. We identified two predicted deleterious missense mutations, p.G84E and p.R217C, that were recurrent among breast cancer cases and further evaluated their association with breast cancer risk in a larger study. Taken together, 4,520 familial non-BRCA1/2 breast cancer cases and 3,127 controls were genotyped including the cases and controls of the whole gene screen. The concordance rate for the genotyping assays compared with Sanger sequencing was 100%. The prostate cancer risk allele p.G84E was identified in 18 (0.56%) of 3,187 cases and 16 (0.70%) of 2,300 controls (OR = 0.81, 95% CI = 0.41-1.59, P = 0.54). Additionally, p.R217C was identified in 10 (0.31%) of 3,208 cases and 2 (0.087%) of 2,288 controls (OR = 3.57, 95% CI = 0.76-33.57, P = 0.14). These results imply that none of the recurrent HOXB13 mutations in the Dutch population are associated with breast cancer risk, although it may be worthwhile to evaluate p.R217C in a larger study.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Wendy J C
authors.initials: WJ
authors.lastname: Prager-van der Smissen
authors.affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: J Margriet
authors.initials: JM
authors.lastname: Collée
authors.affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Sten
authors.initials: S
authors.lastname: Cornelissen
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Roy
authors.initials: R
authors.lastname: Lamping
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Anja
authors.initials: A
authors.lastname: Nieuwlaat
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.affiliation: Division of Diagnostic Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Senno
authors.initials: S
authors.lastname: Verhoef
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Ans M W
authors.initials: AM
authors.lastname: van den Ouweland
authors.affiliation: Division of Diagnostic Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Frans B L
authors.initials: FB
authors.lastname: Hogervorst
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.|Cancer Genomics Netherlands, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hollestelle
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk
chemical_list: C484414:HOXB13 protein, human; D018398:Homeodomain Proteins