Innate immunity gene polymorphisms and the risk of colorectal neoplasia
Innate immunity gene polymorphisms and the risk of colorectal neoplasia
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DOI：
10.1093/carcin/bgt228
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发表时间：
2013-11-01
期刊：
影响因子：
4.7
通讯作者：
Berndt, Sonja I.
中科院分区：
文献类型：
--
作者：
Chang, Cindy M.;Chia, Victoria M.;Berndt, Sonja I.
调节先天免疫和炎症的基因的遗传变异可能导致结直肠肿瘤风险。为了评估这种关联，我们在前列腺、肺、结肠直肠和卵巢癌筛查试验中对451例结肠直肠癌病例、694例晚期结肠直肠腺瘤病例和696例对照欧洲血统进行了巢式病例对照研究。共评估了98个基因的935个标签单核苷酸多态性（SNP）。Logistic回归分析用于估计与结直肠肿瘤相关性的比值比（OR）和95%置信区间（CI）。16个SNPs与结直肠肿瘤风险相关，P < 0.01，但经多重检验校正后，仅rs 2838732（ITGB 2）仍与结直肠肿瘤相关（OR每T等位基因0.68，95% CI：0.57 - 0.83，P 7.7 10（5），校正P 0.07）。ITGB 2编码整合素β链家族中的CD 18蛋白。ITGB 2与结直肠癌的关联性（OR每T等位基因0.41，95%CI：0.300.55，P 2.4 10（9））强于与腺瘤的关联性（OR每T等位基因0.84，95%CI：0.691.03，P 0.08），但在验证研究中未重复。吸烟状态显著改变了ITGB 2 rs 2838732相关性（相互作用的P值为0.003）。在从不吸烟者和曾经吸烟者中，它与结直肠肿瘤呈负相关（OR/T等位基因分别为0.5，95% CI：0.37 - 0.69和OR/T等位基因分别为0.72，95% CI：0.54 - 0.95），但在目前吸烟者中未观察到相关性。在BPI/LBP和MYD 88中观察到SNP的其他显著发现。虽然结果需要重复，但我们的研究结果表明，炎症相关基因的遗传变异可能与结直肠肿瘤的风险有关。
Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested casecontrol study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (ORper T allele 0.68, 95% CI: 0.570.83, P 7.7 10(5), adjusted P 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (ORper T allele 0.41, 95% CI: 0.300.55, P 2.4 10(9)) than for adenoma (ORper T allele 0.84, 95%CI: 0.691.03, P 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (ORper T allele 0.5, 95% CI: 0.370.69 and ORper T allele 0.72, 95% CI: 0.540.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammation-related genes may be related to the risk of colorectal neoplasia.