Genes & Nutrition

, Volume 8, Issue 1, pp 115–126 | Cite as

PTGS1, PTGS2, ALOX5, ALOX12, ALOX15, and FLAP SNPs: interaction with fatty acids in colon cancer and rectal cancer

  • Nina Habermann
  • Cornelia M. Ulrich
  • Abbie Lundgreen
  • Karen W. Makar
  • Elizabeth M. Poole
  • Bette Caan
  • Richard Kulmacz
  • John Whitton
  • Rachel Galbraith
  • John D. Potter
  • Martha L. Slattery
Research Paper

Abstract

Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Oxygenation of omega-6 PUFAs generally results in the production of pro-inflammatory mediators, whereas oxygenated products of omega-3 (n-3) PUFAs generally have lower inflammatory activity. We hypothesize that elevated n-3 PUFA intakes from fish are associated with lower risk of colorectal cancer among those with genetic variants that result in higher levels of pro-inflammatory mediators. In population-based case–control studies of colon (case n = 1,574) and rectal cancer (case n = 791) and disease-free controls (n = 2,969), we investigated interactions between dietary fatty acid intake and 107 candidate polymorphisms and tagSNPs in PTGS1, PTGS2, ALOX12, ALOX5, ALOX15, and FLAP. The two studies used an identical genotyping protocol. We observed interactions and statistically significant increases in colon cancer risk for low docosahexaenoic acid intake among those with the PTGS1 rs10306110 (−1,053 A > G) variant genotypes (OR = 1.6, 95 % confidence interval = 1.1–2.3, adj. p = 0.06) and rectal cancer risk for low total fat intake among those with the variant PTGS1 rs10306122 (7,135 A > G) (ORvs.wt = 1.80, 1.02–2.99; adj. p = 0.08). The ALOX15 rs11568131 (10,339 C > T) wild type in combination with a high inflammation score (low EPA intake, high AA intake, no regular NSAID use, high BMI, smoking) was associated with increased colon cancer risk (OR = 2.28, 1.7–3.07). Rectal cancer risk was inversely associated with a low inflammation score among PTGS2 rs4648276 (3,934 T > C) variant allele carriers (OR = 0.49, 0.25–0.75). Overall, these data provide some modest evidence for interactions between dietary fat intake and genetic variation in genes involved in eicosanoid metabolism and colorectal cancer risk.

Keywords

Colon cancer Rectal cancer Genetic variants Fatty acid intake 

Supplementary material

12263_2012_302_MOESM1_ESM.docx (33 kb)
Supplementary material 1 (DOCX 32 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Nina Habermann
    • 1
    • 2
  • Cornelia M. Ulrich
    • 1
    • 2
  • Abbie Lundgreen
    • 3
  • Karen W. Makar
    • 4
  • Elizabeth M. Poole
    • 5
    • 6
  • Bette Caan
    • 7
  • Richard Kulmacz
    • 8
  • John Whitton
    • 4
  • Rachel Galbraith
    • 4
  • John D. Potter
    • 4
  • Martha L. Slattery
    • 3
  1. 1.National Center for Tumor DiseasesHeidelbergGermany
  2. 2.German Cancer Research CenterHeidelbergGermany
  3. 3.Department of Medicine, School of MedicineUniversity of UtahSalt Lake CityUSA
  4. 4.Fred Hutchinson Cancer Research CenterSeattleUSA
  5. 5.Channing Laboratory, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  6. 6.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  7. 7.Kaiser Permanente Medical Research Program, Department of ResearchOaklandUSA
  8. 8.University of Texas Health Science Center at HoustonHoustonUSA

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