gms | German Medical Science

MAINZ//2011: 56. GMDS-Jahrestagung und 6. DGEpi-Jahrestagung

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e. V.
Deutsche Gesellschaft für Epidemiologie e. V.

26. - 29.09.2011 in Mainz

Phospholipase A2A polymorphisms and risk of colorectal neoplasia

Meeting Abstract

  • Clare Abbenhardt - Nationales Centrum für Tumorerkrankungen/Deutsches Krebsforschungszentrum, Heidelberg
  • Elizabeth M Poole - Channing Laboratory, Department of Medicine, Bringham and Women's Hospital Harvard Medical School, Boston, MA
  • Liren Xiao - Fred Hutchinson Cancer Research Center, Seattle, WA
  • Martha L Slattery - University of Utah, School of Medicine, Department of Medicine, Salt Lake City, UT
  • Rachel L Galbraith - Fred Hutchinson Cancer Research Center, Seattle, WA
  • David Duggan - Translational Genomics Research Institute, Phoenix, AZ
  • Karen W Makar - Fred Hutchcinson Cancer Research Center, Seattle, WA
  • Richard J Kulmacz - University of Texas Health Science Center at Houston, Houston TX
  • Karen Curtin - University of Utah, School of Medicine, Department of Medicine, Salt Lake City, UT
  • John D Potter - Fred HUtchinson Cancer Research Center, Seattle, WA
  • Bette J Caan - Kaiser Permanente Medical Research Program, Department of Research, Oakland, CA
  • Jill Muehling - Translational Genomics Research Institute, Phoenix, AZ
  • Darren Taverna - Translational Genomics Research Institute, Phoenix, AZ
  • Christopher S Carlson - Fred Hutchinson Cancer Reserach Center, Seattle, WA
  • Cornelia M Ulrich - Nationales Centrum für Tumorerkrankungen/Deutsches Krebsforschungszentrum, Heidelberg

Mainz//2011. 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi). Mainz, 26.-29.09.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11gmds306

doi: 10.3205/11gmds306, urn:nbn:de:0183-11gmds3063

Veröffentlicht: 20. September 2011

© 2011 Abbenhardt et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Pancreatic phospholipase A2 (also known as PLA2G1B or PLA2A) catalyzes the release of fatty acids from dietary phospholipids for adsorption in the small intestine. Some of the polyunsaturated fatty acids removed from the intestinal lumen are precursors to eicosanoids, which are linked to inflammation, cell proliferation and colorectal carcinogenesis. We suspect that genetic variation at the PLA2A locus might affect colorectal neoplasia and thus we evaluated the association of PLA2A tagSNPs with colorectal neoplasia risk in three independent study populations capturing the range of colorectal carcinogenesis.

Methods: A linkage-disequilibrium (LD)-based tagSNP selection algorithm (r2=0.90, MAF=4%) identified 3 tagSNPs in PLA2A. We genotyped these SNPs on the same Illumina platform in 3 US population-based case-control studies of colon cancer (1424 cases/1780 controls), rectal cancer (583 cases/775 controls), and colorectal adenomas (485 cases/578 controls). LD was calculated among Caucasian controls for each study. For gene-level associations, we conducted principal components analysis (PCA) and haplotype analysis. Multiple logistic regression was used for single SNPs, adjusting for age, sex, and study site. To avoid confounding by race, we restricted our analyses to Caucasians (>90% of all study populations).

Results: Two PLA2A variants were statistically significantly associated with reduced risk of rectal cancer (rs5637, 3702G>A Ser98Ser, p-trend = 0.03 and rs9657930, 1593C>T p-trend = 0.01, see table). Linkage disequilibrium between the SNPs was modest (r2<0.6). Principal component analysis was significant (p=0.02). No statistically significant associations were observed with colon cancer or colorectal polyps overall; however, there was significant heterogeneity by tumor site for polyps (p= 0.01).

Conclusion: The results suggest that genetic variability in PLA2A affects susceptibility to rectal but not colon cancer. Additional observational and functional follow-up studies are needed.

Table 1 [Tab. 1].


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