BACKGROUND: Prostaglandins are important inflammatory mediators; prostaglandin E2 (PGE2) is the predominant prostaglandin in colorectal neoplasia and affects colorectal carcinogenesis. Prostaglandins are metabolites of omega-6 and omega-3 polyunsaturated fatty acids; their biosynthesis is the primary target of nonsteroidal anti-inflammatory drugs (NSAID), which reduce colorectal neoplasia risk. METHODS: We investigated candidate and tagSNPs in PGE2 synthase (PGES), PGE2 receptors (EP2 and EP4), and prostaglandin dehydrogenase (PGDH) in a case-control study of adenomas (n = 483) versus polyp-free controls (n = 582) and examined interactions with NSAID use or fish intake, a source of omega-3 fatty acids. RESULTS: A 30% adenoma risk reduction was observed for EP2 4950G>A (intron 1; OR(GA/AA vs. GG), 0.71; 95% confidence interval, 0.52-0.99). For the candidate polymorphism EP4 Val294Ile, increasing fish intake was associated with increased adenoma risk among those with variant genotypes, but not among those with the Val/Val genotype (P(interaction) = 0.02). An interaction with fish intake was also observed for PGES -664A>T (5' untranslated region; P(interaction) = 0.01). Decreased risk with increasing fish intake was only seen among those with the AT or TT genotypes (OR(>2 t/wk vs. <1 t/wk), 0.56; 95% confidence interval, 0.28-1.13). We also detected interactions between NSAIDs and EP2 9814C>A (intron 1) and PGDH 343C>A (intron 1). However, none of the observed associations was statistically significant after adjustment for multiple testing. We investigated potential gene-gene interactions using the Chatterjee 1 degree of freedom Tukey test and logic regression; neither method detected significant interactions. CONCLUSIONS: These data provide little support for associations between adenoma risk and genetic variability related to PGE(2), yet suggest gene-environment interactions with anti-inflammatory exposures.
BACKGROUND:Prostaglandins are important inflammatory mediators; prostaglandin E2 (PGE2) is the predominant prostaglandin in colorectal neoplasia and affects colorectal carcinogenesis. Prostaglandins are metabolites of omega-6 and omega-3 polyunsaturated fatty acids; their biosynthesis is the primary target of nonsteroidal anti-inflammatory drugs (NSAID), which reduce colorectal neoplasia risk. METHODS: We investigated candidate and tagSNPs in PGE2 synthase (PGES), PGE2 receptors (EP2 and EP4), and prostaglandin dehydrogenase (PGDH) in a case-control study of adenomas (n = 483) versus polyp-free controls (n = 582) and examined interactions with NSAID use or fish intake, a source of omega-3 fatty acids. RESULTS: A 30% adenoma risk reduction was observed for EP2 4950G>A (intron 1; OR(GA/AA vs. GG), 0.71; 95% confidence interval, 0.52-0.99). For the candidate polymorphism EP4Val294Ile, increasing fish intake was associated with increased adenoma risk among those with variant genotypes, but not among those with the Val/Val genotype (P(interaction) = 0.02). An interaction with fish intake was also observed for PGES -664A>T (5' untranslated region; P(interaction) = 0.01). Decreased risk with increasing fish intake was only seen among those with the AT or TT genotypes (OR(>2 t/wk vs. <1 t/wk), 0.56; 95% confidence interval, 0.28-1.13). We also detected interactions between NSAIDs and EP2 9814C>A (intron 1) and PGDH 343C>A (intron 1). However, none of the observed associations was statistically significant after adjustment for multiple testing. We investigated potential gene-gene interactions using the Chatterjee 1 degree of freedom Tukey test and logic regression; neither method detected significant interactions. CONCLUSIONS: These data provide little support for associations between adenoma risk and genetic variability related to PGE(2), yet suggest gene-environment interactions with anti-inflammatory exposures.
Authors: Cornelia M Ulrich; Jeannette Bigler; Rachel Sparks; John Whitton; Justin G Sibert; Ellen L Goode; Yutaka Yasui; John D Potter Journal: Cancer Epidemiol Biomarkers Prev Date: 2004-05 Impact factor: 4.254
Authors: Elizabeth M Poole; Jeannette Bigler; John Whitton; Justin G Sibert; Richard J Kulmacz; John D Potter; Cornelia M Ulrich Journal: Carcinogenesis Date: 2007-02-02 Impact factor: 4.944
Authors: C M Ulrich; E Kampman; J Bigler; S M Schwartz; C Chen; R Bostick; L Fosdick; S A Beresford; Y Yasui; J D Potter Journal: Cancer Epidemiol Biomarkers Prev Date: 1999-08 Impact factor: 4.254
Authors: John A Baron; Bernard F Cole; Robert S Sandler; Robert W Haile; Dennis Ahnen; Robert Bresalier; Gail McKeown-Eyssen; Robert W Summers; Richard Rothstein; Carol A Burke; Dale C Snover; Timothy R Church; John I Allen; Michael Beach; Gerald J Beck; John H Bond; Tim Byers; E Robert Greenberg; Jack S Mandel; Norman Marcon; Leila A Mott; Loretta Pearson; Fred Saibil; Rosalind U van Stolk Journal: N Engl J Med Date: 2003-03-06 Impact factor: 91.245
Authors: W C Willett; L Sampson; M J Stampfer; B Rosner; C Bain; J Witschi; C H Hennekens; F E Speizer Journal: Am J Epidemiol Date: 1985-07 Impact factor: 4.897
Authors: Ulrike Haug; Elizabeth M Poole; Liren Xiao; Karen Curtin; David Duggan; Li Hsu; Karen W Makar; Ulrike Peters; Richard J Kulmacz; John D Potter; Lisel Koepl; Bette J Caan; Martha L Slattery; Cornelia M Ulrich Journal: Genes Chromosomes Cancer Date: 2012-02-27 Impact factor: 5.006
Authors: Karen W Makar; Elizabeth M Poole; Alexa J Resler; Brenna Seufert; Karen Curtin; Sarah E Kleinstein; David Duggan; Richard J Kulmacz; Li Hsu; John Whitton; Christopher S Carlson; Christine F Rimorin; Bette J Caan; John A Baron; John D Potter; Martha L Slattery; Cornelia M Ulrich Journal: Cancer Causes Control Date: 2013-12 Impact factor: 2.506
Authors: Zora Djuric; D Kim Turgeon; Ananda Sen; Jianwei Ren; Kirk Herman; Devon Ramaswamy; Lili Zhao; Mack T Ruffin; Daniel P Normolle; William L Smith; Dean E Brenner Journal: Cancer Prev Res (Phila) Date: 2017-11-13
Authors: Alexa J Resler; Karen W Makar; Laura Heath; John Whitton; John D Potter; Elizabeth M Poole; Nina Habermann; Dominique Scherer; David Duggan; Hansong Wang; Noralane M Lindor; Michael N Passarelli; John A Baron; Polly A Newcomb; Loic Le Marchand; Cornelia M Ulrich Journal: Carcinogenesis Date: 2014-06-07 Impact factor: 4.944
Authors: Todd L Edwards; Martha J Shrubsole; Qiuyin Cai; Guoliang Li; Qi Dai; Douglas K Rex; Thomas M Ulbright; Zhenming Fu; Harvey J Murff; Walter Smalley; Reid Ness; Wei Zheng Journal: Cancer Prev Res (Phila) Date: 2012-05-02
Authors: Suzanna M Zick; D Kim Turgeon; Shaiju K Vareed; Mack T Ruffin; Amie J Litzinger; Benjamin D Wright; Sara Alrawi; Daniel P Normolle; Zora Djuric; Dean E Brenner Journal: Cancer Prev Res (Phila) Date: 2011-10-11
Authors: Sarah Kraus; Simone Hummler; Nadir Arber; Cornelia M Ulrich; Adetunji T Toriola; Elizabeth M Poole; Dominique Scherer; Jana Kotzmann; Karen W Makar; Dina Kazanov; Lior Galazan; Inna Naumov; Anna E Coghill; David Duggan; Biljana Gigic Journal: Pharmacogenet Genomics Date: 2013-08 Impact factor: 2.089
Authors: Brenna L Seufert; Elizabeth M Poole; John Whitton; Liren Xiao; Karen W Makar; Peter T Campbell; Richard J Kulmacz; John A Baron; Polly A Newcomb; Martha L Slattery; John D Potter; Cornelia M Ulrich Journal: Carcinogenesis Date: 2012-09-22 Impact factor: 4.944
Authors: Sarah E Kleinstein; Laura Heath; Karen W Makar; Elizabeth M Poole; Brenna L Seufert; Martha L Slattery; Liren Xiao; David J Duggan; Li Hsu; Karen Curtin; Lisel Koepl; Jill Muehling; Darin Taverna; Bette J Caan; Christopher S Carlson; John D Potter; Cornelia M Ulrich Journal: Genes Chromosomes Cancer Date: 2013-02-12 Impact factor: 5.006