Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants

Author:

Campbell Peter T1ORCID,Lin Yi2,Bien Stephanie A2,Figueiredo Jane C34,Harrison Tabitha A2ORCID,Guinter Mark A1ORCID,Berndt Sonja I5,Brenner Hermann678,Chan Andrew T910111213,Chang-Claude Jenny1415,Gallinger Steven J16,Gapstur Susan M1,Giles Graham G171819ORCID,Giovannucci Edward1320,Gruber Stephen B21,Gunter Marc22,Hoffmeister Michael6ORCID,Jacobs Eric J1ORCID,Jenkins Mark A18ORCID,Le Marchand Loic23,Li Li24,McLaughlin John R25,Murphy Neil22,Milne Roger L171819ORCID,Newcomb Polly A2,Newton Christina1,Ogino Shuji12132627ORCID,Potter John D2ORCID,Rennert Gad282930ORCID,Rennert Hedy S282930,Robinson Jennifer31,Sakoda Lori C232ORCID,Slattery Martha L33,Song Yiqing34ORCID,White Emily235,Woods Michael O36ORCID,Casey Graham37,Hsu Li2,Peters Ulrike235

Affiliation:

1. Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA

2. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

3. Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

4. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

5. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

6. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

7. Division of Preventive Oncology, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT), Heidelberg, Germany

8. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

9. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

10. Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

11. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA

12. Broad Institute of Harvard and MIT, Cambridge, MA, USA

13. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA

14. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

15. University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany

16. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

17. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia

18. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia

19. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia

20. Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA

21. Center for Precision Medicine and Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA

22. Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France

23. University of Hawaii Cancer Center, Honolulu, HI, USA

24. Department of Family Medicine and Cancer Center, University of Virginia, Charlottesville, VA, USA

25. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

26. Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

27. Department of Pathology, Brigham & Women’s Hospital, and Harvard Medical School, Boston, MA, USA

28. Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel

29. Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

30. Clalit National Cancer Control Center, Haifa, Israel

31. Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA

32. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

33. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

34. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA

35. Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA

36. Discipline of Genetics, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada

37. Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA

Abstract

Abstract Background Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. Methods We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. Results Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10–17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10–24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10–10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10–10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10–8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes. Conclusion These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3