身高与结直肠癌风险的孟德尔随机化研究。
Mendelian randomization study of height and risk of colorectal cancer.
作者信息
Thrift Aaron P, Gong Jian, Peters Ulrike, Chang-Claude Jenny, Rudolph Anja, Slattery Martha L, Chan Andrew T, Esko Tonu, Wood Andrew R, Yang Jian, Vedantam Sailaja, Gustafsson Stefan, Pers Tune H, Baron John A, Bezieau Stéphane, Küry Sébastien, Ogino Shuji, Berndt Sonja I, Casey Graham, Haile Robert W, Du Mengmeng, Harrison Tabitha A, Thornquist Mark, Duggan David J, Le Marchand Loic, Lemire Mathieu, Lindor Noralane M, Seminara Daniela, Song Mingyang, Thibodeau Stephen N, Cotterchio Michelle, Win Aung Ko, Jenkins Mark A, Hopper John L, Ulrich Cornelia M, Potter John D, Newcomb Polly A, Schoen Robert E, Hoffmeister Michael, Brenner Hermann, White Emily, Hsu Li, Campbell Peter T
机构信息
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA, Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Estonian Genome Center, University of Tartu, Tartu, Estonia, Divisions of Endocrinology and Genetics and Center for Basic Translational Obesity Research, Boston Children's Hospital, Boston, MA, USA, Department of Genetics, Harvard Medical School, Boston, MA, USA, Broad Institute, Cambridge, MA, USA, Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK, Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia, University of Queensland Diamantina Institute, Translation Research Institute, Brisbane, QLD, Australia, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA, CHU Nantes, Service de Génétique Médicale, Nantes, France, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, USC Norris
出版信息
Int J Epidemiol. 2015 Apr;44(2):662-72. doi: 10.1093/ije/dyv082. Epub 2015 May 20.
BACKGROUND
For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk.
METHODS
To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10,226 CRC cases and 10,286 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height, genetically predicted height and CRC.
RESULTS
Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = .01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15).
CONCLUSION
We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies.
背景
对于男性和女性而言，较高的身高与所有癌症综合发病风险的增加相关。对于结直肠癌（CRC），尚不清楚身高与性别的差异关联是真实存在的，还是由于观察性研究中固有的混杂因素或偏差所致。我们开展了一项孟德尔随机化研究，以检验身高与结直肠癌风险之间的关联。
方法
为尽量减少混杂因素和偏差，我们在10226例结直肠癌病例和10286例对照中，推导了一个预测身高的加权遗传风险评分（使用696个与身高相关的基因变异）。采用逻辑回归来估计身高、基因预测身高与结直肠癌之间关联的比值比（OR）和95%置信区间（95%CI）。
结果
使用传统方法，身高增加（每增加10厘米）与结直肠癌风险增加相关（OR = 1.08，95%CI = 1.02 - 1.15）。在按性别进行的分析中，身高与女性结直肠癌风险相关（OR = 1.15，95%CI = 1.05 - 1.26），但与男性无关（OR = 0.98，95%CI = 0.92 - 1.05）。与这些结果一致，携带更多（加权）增加身高的等位基因（每增加1个单位）与女性和男性综合结直肠癌风险较高相关（OR = 1.07，95%CI = 1.01 - 1.14），与女性相关（OR = 1.09，95%CI = 1.01 - 1.19）。男性存在关联的证据较弱（OR = 1.05，95%CI = 0.96 - 1.15）。
结论
我们提供了身高与女性结直肠癌之间存在因果关联的证据。男性结直肠癌与身高的关联仍不明确，需要在其他大型研究中进一步调查。
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