Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study.
Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study.
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DOI：
10.1186/1471-2407-9-407
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发表时间：
2009-11-21
期刊：
影响因子：
3.8
通讯作者：
Vogel U
中科院分区：
文献类型：
--
作者：
Andersen V;Ostergaard M;Christensen J;Overvad K;Tjønneland A;Vogel U
外源性转运蛋白、多药耐药1 (MDR1/ABCB1) 和乳腺癌耐药蛋白(BCRP/ABCG2) 可能会限制肠道吸收各种致癌物，包括杂环胺(HCA) 和多环芳烃(PAH)。 Cyclooxygenase-2 (COX-2) derived prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness.本研究的目的是调查这些基因的多态性是否与结直肠癌 (CRC) 风险相关，并调查与吸烟、肉类消费和非甾体抗炎药使用等生活方式因素之间可能的相互作用。分析了以下多态性；外显子 26 中的同义 MDR1 C3435T (rs1045642)、内含子 3 中的 G-rs3789243-A、功能性 BCRP C421A (rs2231142)、启动子区域中的两个 COX-2 A-1195G (rs689466) 和 G-765C (rs20417) 以及 COX-2 T8473C (rs5275) polymorphisms in the 3'-untranslated region.在一项包含 359 例病例的巢式病例队列研究和来自丹麦前瞻性饮食、癌症与健康研究的 765 名参与者的随机队列样本中，对多态性与生活方式因素进行了评估。 MDR1 内含子 3 多态性变异等位基因携带者患 CRC 的风险比纯合野生型等位基因携带者高 1.52 倍（发病率比 (IRR) = 1.52，95% 置信区间 (CI)：1.12-2.06）。 Carriers of the variant allele of MDR1 C3435T exon 26 had a lower risk of CRC than homozygous C-allele carriers (IRR = 0.71 (CI:0.50-1.00)).这些 MDR1 多态性与红肉和加工肉类的摄入量之间存在相互作用，与 CRC 风险相关。纯合 MDR1 C3435T C 等位基因携带者每天摄入 25 克肉后，风险增加 8%（CI：1.00-1.16），而变异等位基因携带者的风险并未增加（交互作用 p = 0.02）。 COX-2 and BCRP polymorphisms were not associated with CRC risk. There was interaction between NSAID use and MDR1 C3435T and COX-2 T8473C (p-values for interaction 0.001 and 0.04, respectively). MDR1 的两个多态性与 CRC 风险相关，并且这些多态性和肉类摄入量与 CRC 风险相关。 Our results suggest that MDR1 polymorphisms affect the relationship between meat and CRC risk.
The xenobiotic transporters, Multidrug Resistance 1 (MDR1/ABCB1) and Breast Cancer Resistance Protein (BCRP/ABCG2) may restrict intestinal absorption of various carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Cyclooxygenase-2 (COX-2) derived prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness. The aim of this study was to investigate if polymorphisms in these genes were associated with risk of colorectal cancer (CRC), and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. The following polymorphisms were analyzed; a synonymous MDR1 C3435T (rs1045642) in exon26, G-rs3789243-A in intron3, the functional BCRP C421A (rs2231142), the two COX-2 A-1195G (rs689466) and G-765C (rs20417) in the promoter region, and the COX-2 T8473C (rs5275) polymorphisms in the 3'-untranslated region. The polymorphisms were assessed together with lifestyle factors in a nested case-cohort study of 359 cases and a random cohort sample of 765 participants from the Danish prospective Diet, Cancer and Health study. Carriers of the variant allele of MDR1 intron 3 polymorphism were at 1.52-fold higher risk of CRC than homozygous wild type allele carriers (Incidence rate ratio (IRR) = 1.52, 95% Confidence Interval (CI): 1.12-2.06). Carriers of the variant allele of MDR1 C3435T exon 26 had a lower risk of CRC than homozygous C-allele carriers (IRR = 0.71 (CI:0.50-1.00)). There was interaction between these MDR1 polymorphisms and intake of red and processed meat in relation to CRC risk. Homozygous MDR1 C3435T C-allele carriers were at 8% increased risk pr 25 gram meat per day (CI: 1.00-1.16) whereas variant allele carriers were not at increased risk (p for interaction = 0.02). COX-2 and BCRP polymorphisms were not associated with CRC risk. There was interaction between NSAID use and MDR1 C3435T and COX-2 T8473C (p-values for interaction 0.001 and 0.04, respectively). Two polymorphisms in MDR1 were associated with CRC risk and there was interaction between these polymorphisms and meat intake in relation to CRC risk. Our results suggest that MDR1 polymorphisms affect the relationship between meat and CRC risk.
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影响因子：
--
作者：
Andersen V;Agerstjerne L;Jensen D;Østergaard M;Saebø M;Hamfjord J;Kure E;Vogel U
通讯作者：
Vogel U
DOI：
10.1016/j.bbapap.2009.02.014
发表时间：
2009-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Fung KL;Gottesman MM
通讯作者：
Gottesman MM
影响因子：
2.8
作者：
Gong, Zhihong;Bostick, Roberd M.;Hebert, James R.
通讯作者：
Hebert, James R.
影响因子：
3.5
作者：
Ho, GT;Soranzo, N;Satsangi, J
通讯作者：
Satsangi, J
影响因子：
5.8
作者：
Albermann, N;Schmitz-Winnenthal, FH;Weiss, J
通讯作者：
Weiss, J