Identifying etiologically distinct sub-types of cancer: A demonstration project involving breast cancer Journal Article

Authors: Begg, C. B.; Orlow, I.; Zabor, E. C.; Arora, A.; Sharma, A.; Seshan, V. E.; Bernstein, J. L.
Article Title: Identifying etiologically distinct sub-types of cancer: A demonstration project involving breast cancer
Abstract: With the advent of increasingly detailed molecular portraits of tumor specimens, much attention has been directed toward identifying clinically distinct subtypes of cancer. Subtyping of tumors can also be accomplished with the goal of identifying distinct etiologies. We demonstrate the use of new methodologies to identify genes that distinguish etiologically heterogeneous subtypes of breast cancer using data from the case-control Cancer and Steroid Hormone Study. Tumor specimens were evaluated using a breast cancer expression panel of 196 genes. Using a statistical measure that distinguishes the degree of etiologic heterogeneity in tumor subtypes, each gene is ranked on the basis of its ability to distinguish etiologically distinct subtypes. This is accomplished independently using case-control comparisons and by examining the concordance odds ratios in double primaries. The estrogen receptor gene, and others in this pathway with expression levels that correlated strongly with estrogen receptor levels, demonstrate high degrees of etiologic heterogeneity in both methods. Our results are consistent with a growing literature that confirms the distinct etiologies of breast cancers classified on the basis of estrogen receptor expression levels. This proof-of-principle project demonstrates the viability of new strategies to identify genomic features that distinguish subtypes of cancer from an etiologic perspective.
Keywords: dna methylation; tumor; lung-cancer; risk-factors; heterogeneity; mammographic density; subtypes; etiologic heterogeneity; risk prediction; receptor status; tumor subtypes; genetic susceptibility loci; molecular pathological epidemiology; double primaries; association consortium
Journal Title: Cancer Medicine
Volume: 4
Issue: 9
ISSN: 2045-7634
Publisher: Wiley Blackwell  
Date Published: 2015-09-01
Start Page: 1432
End Page: 1439
Language: English
ACCESSION: WOS:000361007400013
DOI: 10.1002/cam4.456
PMCID: PMC4567028
PUBMED: 25974664
Notes: Article -- Source: Wos
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    285 Seshan
  2. Colin B Begg
    238 Begg
  3. Irene Orlow
    191 Orlow
  4. Emily Craig Zabor
    131 Zabor
  5. Jonine L Bernstein
    103 Bernstein
  6. Ajay P Sharma
    7 Sharma
  7. Arshi Arora
    20 Arora