Passarelli Michael N, Newcomb Polly A, Makar Karen W, Burnett-Hartman Andrea N, Potter John D, Upton Melissa P, Zhu Lee-Ching, Rosenfeld Michael E, Schwartz Stephen M, Rutter Carolyn M
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-B402, Seattle, WA, 98109, USA.
Cancer Causes Control. 2015 Mar;26(3):467-73. doi: 10.1007/s10552-015-0526-3. Epub 2015 Jan 25.
Studies linking cholesterol levels to the development of colorectal neoplasia are inconsistent, and Mendelian randomization has been suggested as a way to help avoid problems with confounding and reverse causation.
We genotyped individuals who received a colonoscopy at Group Health (1998-2007) for 96 of 102 single-nucleotide polymorphisms identified by the Global Lipids Genetics Consortium. Participants included 139 advanced adenoma cases, 518 non-advanced adenoma cases, 380 non-adenomatous polyp cases, and 754 polyp-free controls. All had at least one available pre-colonoscopy lipid measurement from electronic records maintained by Group Health.
Advanced adenoma cases were more likely than controls to have higher pre-colonoscopy zenith low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (odds ratio, OR per 20 mg/dL LDL increase: 1.16, 95 % confidence interval, CI 1.03-1.30; per 40 mg/dL TG increase: 1.09, 1.03-1.16; and per 20 mg/dL TC increase: 1.09, 1.02-1.18). For these traits, genotype-polyp ORs using weighted allele scores were not statistically significant (OR per increase in score scaled to a 20 mg/dL LDL increase: 1.17, 0.78-1.75; a 40 mg/dL TG increase: 1.12, 0.91-1.38; a 20 mg/dL TC increase: 0.99, 0.71-1.38).
Cholesterol levels may be associated with advanced adenomas, but larger studies are warranted to determine whether this association can be attributed to genetics.
有关胆固醇水平与结直肠肿瘤发生之间联系的研究结果并不一致，孟德尔随机化已被提议作为一种有助于避免混杂因素和反向因果关系问题的方法。
我们对在健康集团（1998 - 2007年）接受结肠镜检查的个体进行基因分型，检测全球脂质遗传学联盟确定的102个单核苷酸多态性中的96个。参与者包括139例进展期腺瘤病例、518例非进展期腺瘤病例、380例非腺瘤性息肉病例和754例无息肉对照。所有人在健康集团维护的电子记录中都至少有一次结肠镜检查前的血脂测量值。
进展期腺瘤病例比对照组更有可能在结肠镜检查前具有更高的顶点低密度脂蛋白（LDL）、甘油三酯（TG）和总胆固醇（TC）水平（优势比，每20mg/dL LDL增加的OR：1.16，95%置信区间，CI 1.03 - 1.30；每40mg/dL TG增加：1.09，1.03 - 1.16；每20mg/dL TC增加：1.09，1.02 - 1.18）。对于这些性状，使用加权等位基因分数的基因型 - 息肉OR无统计学意义（每增加一个分数，按20mg/dL LDL增加进行标度的OR：1.17，0.78 - 1.75；40mg/dL TG增加：1.12，0.91 - 1.38；20mg/dL TC增加：0.99，0.71 - 1.38）。
胆固醇水平可能与进展期腺瘤有关，但需要更大规模的研究来确定这种关联是否可归因于遗传学。
