Genetic variation in ALCAM and other chromosomal instability genes in breast cancer survival View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-09-21

AUTHORS

Verena Varadi, Melanie Bevier, Ewa Grzybowska, Robert Johansson, Kerstin Enquist-Olsson, Roger Henriksson, Dorota Butkiewicz, Jolanta Pamula-Pilat, Karolina Tecza, Kari Hemminki, Per Lenner, Asta Försti

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. More... »

PAGES

311-319

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-011-1765-y

DOI

http://dx.doi.org/10.1007/s10549-011-1765-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020737578

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21935604


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33 schema:description 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.
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40 ALCAM gene
41 BC
42 BC cases
43 BC-specific survival
44 Polish population
45 Swedish population
46 aggressive tumor characteristics
47 allele carriers
48 alleles
49 association
50 basis
51 breast cancer risk
52 breast cancer survival
53 breast tumors
54 cancer
55 cancer patients
56 cancer risk
57 cancer survival
58 carriers
59 cases
60 chance
61 characteristics
62 chromosomal instability
63 clinical outcomes
64 differences
65 disease progression
66 early-onset BC
67 etiological differences
68 event-free survival
69 expression status
70 genes
71 genetic variants
72 genetic variation
73 hallmark
74 higher stage
75 homozygous carriers
76 hr
77 identification
78 instability
79 larger tumor size
80 list
81 lymph node metastasis
82 metastasis
83 minor allele
84 minor allele carriers
85 node metastasis
86 nucleotide polymorphisms
87 outcomes
88 patients
89 polymorphism
90 population
91 population-based series
92 positive lymph node metastasis
93 potential
94 progression
95 results
96 risk
97 series
98 significant association
99 single nucleotide polymorphisms
100 size
101 stage
102 status
103 survival
104 target genes
105 tumor characteristics
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