花生四烯酸脂氧合酶(ALOX)和环氧合酶(COX)多态性和结肠癌的风险。
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古德曼我,鲍曼ED Chanock SJ,阿尔贝里AJ,哈里斯CC
花生四烯酸脂氧合酶(ALOX)和环氧合酶(COX)多态性和结肠癌的风险。
致癌作用。2004年12月25日(12):2467 - 72。Epub 2004年8月12日。
- PubMed ID
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15308583 (在PubMed]
- 文摘
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在人类结肠癌、花生四烯酸代谢主要是通过环氧合酶(COX)和花生四烯酸脂氧合酶(ALOX)生物活性脂质,与结肠癌风险。几个多态性在ALOX和考克斯基因已经被鉴定,包括g - 1752 a、g - 1699 a和Glu254Lys ALOX5;Gln261Arg ALOX12;Leu237Met和Val481Ile COX1;和c - 645 t, COX2 Val511Ala。因为花生四烯酸代谢的重要作用在结肠癌,我们假设这些多态性可能影响对结肠癌。我们解决这个假设在非洲裔和白人使用结肠癌病例(n = 293)和医院- (n = 229)和以人群为基础的(n = 304)对照组。多态性对照组没有差异(P > 0.05);因此,他们结合起来分析。ALOX5 Glu254Lys COX2 c - 645 t和Val511Ala等位基因频率白种人和黑人控制之间的不同(P < 0.001)。 The ALOX5 -1752 and -1699 polymorphisms were in linkage disequilibrium (P < 0.001) and associated with a decreased risk in Caucasians in ALOX5 haplotype analyses (P = 0.03). Furthermore, an inverse association was observed between A alleles at positions -1752 and -1699 of ALOX5 and colon cancer risk in Caucasians, but not in African-Americans. Caucasians with A alleles at ALOX5 -1752 had a reduced odds of colon cancer versus those with G alleles [odds ratio (OR) (GA versus GG), 0.63; 95% confidence interval (CI), 0.39-1.01; OR (AA versus GG), 0.33; 95% CI, 0.07-1.65, P(trend) = 0.02]. Similar results were observed for ALOX5 G-1699A [OR (GA versus GG), 0.59, 95% CI, 0.37-0.94; OR (AA versus GG), 0.27, 95% CI, 0.06-1.32, P(trend) = 0.01]. Statistically significant associations with colon cancer were not observed for the other polymorphisms investigated. We have shown for the first time that a haplotype containing ALOX5 G-1752A and G-1699A in a negative regulatory region of the promoter may influence colon cancer risk in Caucasians.