title: Single nucleotide polymorphisms in chromosomal instability genes and risk and clinical outcome of breast cancer: a Swedish prospective case-control study.
abstract: Chromosomal instability (CIN) is a major characteristic of many cancers. We investigated whether putatively functional single nucleotide polymorphisms (SNPs) in genes related to CIN (CENPF, ESPL1, NEK2, PTTG1, ZWILCH, ZWINT) affect breast cancer (BC) risk and clinical outcome in a Swedish cohort of 749 incident BC cases with detailed clinical data and up to 15 years of follow-up and 1493 matched controls. As a main observation, carriers of the A allele of the CENPF SNP rs438034 had a worse BC-specific survival compared to the wild type genotype GG carriers (hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.19-5.90), although they were less likely to have regional lymph node metastases (odds ratio (OR) 0.71, 95% CI 0.51-1.01) and tumours of stage II-IV (OR 0.73, 95% CI 0.54-0.99). As there is increasing evidence that CENPF is associated with poor prognosis in patients with primary BC, further independent studies are needed to clarify the importance of genetic variation in the CENPF gene in the clinic.
authors.affiliation: Division of Molecular Genetic Epidemiology C050, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Brendle
authors.forename: Andreas
authors.initials: A
authors.lastname: Brandt
authors.forename: Robert
authors.initials: R
authors.lastname: Johansson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Enquist
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Per
authors.initials: P
authors.lastname: Lenner
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D043171:Chromosomal Instability / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology
chemical_list: D005819:Genetic Markers