title: Genetic variation in ALCAM and other chromosomal instability genes in breast cancer survival.
abstract: Chromosomal instability is a hallmark of many cancers and it has a potential to predict clinical outcome of a cancer patient. We hypothesized that genes whose expression status differs between chromosomal stable and unstable breast tumors represent target genes for the identification of genetic variants predicting breast cancer (BC) risk, disease progression, and survival. We used a published list of 38 genes associated with chromosomal instability as a basis for searching potentially functional and informative tagging single nucleotide polymorphisms (SNPs). As a result, 33 SNPs in 16 genes were genotyped in a population-based series of 783 Swedish BC cases. Two SNPs in the ALCAM gene associated with BC-specific survival. For rs1044243, the HR was 4.35 (95% CI 1.34-14.18), and for rs1157, the HR was 3.42 (95% CI 1.32-8.83) for the homozygous carriers of the minor alleles. For the minor allele carriers of CCL18 SNP rs14304, we observed a significant association with aggressive tumor characteristics: large tumor size (OR 1.53, 95% CI 1.10-2.14), positive lymph node metastasis (OR 1.75, 95% CI 1.02-3.00), and high stage (OR 1.37, 95% CI 1.02-1.85). In a Polish population consisting of 506 familial/early onset BC cases, no association with event-free survival for the ALCAM SNPs nor any association with tumor characteristics for the CCL18 SNP were observed, suggesting either a chance finding in the Swedish population or population-based or etiological differences between sporadic and familial/early onset BC.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, DKFZ, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany, v.varadi@dkfz-heidelberg.de
authors.forename: Verena
authors.initials: V
authors.lastname: Varadi
authors.forename: Melanie
authors.initials: M
authors.lastname: Bevier
authors.forename: Ewa
authors.initials: E
authors.lastname: Grzybowska
authors.forename: Robert
authors.initials: R
authors.lastname: Johansson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Enquist-Olsson
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: Jolanta
authors.initials: J
authors.lastname: Pamula-Pilat
authors.forename: Karolina
authors.initials: K
authors.lastname: Tecza
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; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D043171:Chromosomal Instability / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005326:Fetal Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012306:Risk; D055815:Young Adult; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule