Journal article

Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk

Zhiyu Xia, Yu-Ru Su, Paneen Petersen, Lihong Qi, Andre E Kim, Jane C Figueiredo, Yi Lin, Hongmei Nan, Lori C Sakoda, Demetrius Albanes, Sonja I Berndt, Stephane Bezieau, Stephanie Bien, Daniel D Buchanan, Graham Casey, Andrew T Chan, David V Conti, David A Drew, Steven J Gallinger, W James Gauderman Show all

CANCER MEDICINE | WILEY | Published : 2020

Abstract

BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology. METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expressio..

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Grants

Awarded by National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services


Awarded by National Institutes of Health


Awarded by NIH/NCI Cancer Center Support Grant


Awarded by University Hospital Center of Nantes (CHU de Nantes)


Awarded by U.S. Public Health Service from the National Cancer Institute, Department of Health and Human Services


Awarded by National Cancer Institute (NCI), National Institutes of Health (NIH)


Awarded by NCI/NIH


Awarded by National Cancer Institute, National Institutes of Health (NCI/NIH), U.S. Department of Health and Human Services


Awarded by National Institutes of Environmental Health Sciences, National Institutes of Health


Awarded by German Research Council


Awarded by German Federal Ministry of Education and Research


Awarded by Damon Runyon Cancer Research Foundation


Awarded by NCI


Awarded by Australian NHMRC


Awarded by National Institutes of Health, U.S. Department of Health and Human Services


Awarded by Interdisciplinary Health Research Team award from the Canadian Institutes of Health Research


Awarded by National Cancer Institute of Canada


Awarded by Genes, Environment and Health Initiative (GEI)


Awarded by NIH


Awarded by NIH GEI


Awarded by Cancer Research UK


Awarded by National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services


Awarded by FEDER funds -a way to build Europe


Awarded by Agency for Management of University and Research Grants (AGAUR) of the Catalan Government


Awarded by Junta de Castilla y Leon


Awarded by Xarxa de Bancs de Tumors de Catalunya - Pla Director d'Oncologia de Catalunya (XBTC), Plataforma Biobancos


Funding Acknowledgements

Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA164930, U01 CA137088, R01 CA059045, R01201407). Genotyping/Sequencing services were provided by the Center for Inherited Disease Research (CIDR) (X01-HG008596 and X-01-HG007585). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268201200008I. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704. ASTERISK: a Hospital Clinical Research Program (PHRC-BRD09/C) from the University Hospital Center of Nantes (CHU de Nantes) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC). The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and by U.S. Public Health Service contract HHSN261201500005C from the National Cancer Institute, Department of Health and Human Services. COLO2&3: National Institutes of Health (R01 CA60987). The Colon Cancer Family Registry (CCFR) Illumina GWAS was supported by funding from the National Cancer Institute (NCI), National Institutes of Health (NIH) (grant numbers U01 CA122839, R01 CA143247). The CCFR participant recruitment and collection of data and biospecimens used in this study were supported by the NCI/NIH (grant number U01 CA167551) and through NCI/NIH cooperative agreements with the following Colon CFR centers: Australasian Colorectal Cancer Family Registry (grant numbers U01 CA074778 and U01/U24 CA097735), USC Consortium Colorectal Cancer Family Registry (grant numbers U01/U24 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (grant number U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (grant number U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (grant number U01/U24 CA074794), and University of Hawaii Colorectal Cancer Family Registry (grant number U01/U24 CA074806) The content of this manuscript does not necessarily reflect the views or policies of the NCI, NIH or any of the collaborating centers in the Colon Cancer Family Registry (CCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government, any cancer registry, or the CCFR. Colorectal Cancer Transdisciplinary (CORECT) Study: The CORECT Study was supported by the National Cancer Institute, National Institutes of Health (NCI/NIH), U.S. Department of Health and Human Services (grant numbers U19 CA148107, R01 CA81488, P30 CA014089, R01 CA197350; P01 CA196569; R01 CA201407) and National Institutes of Environmental Health Sciences, National Institutes of Health (grant number T32 ES013678). CPS-II: The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort. This study was conducted with Institutional Review Board approval. DACHS: This work was supported by the German Research Council (BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, HO 5117/2-1, HE 5998/2-1, KL 2354/3-1, RO 2270/8-1 and BR 1704/17-1), the Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany, and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01ER1505A and 01ER1505B).DALS: National Institutes of Health (R01 CA48998 to M. L. Slattery). Harvard cohorts (HPFS, NHS, PHS): HPFS is supported by the National Institutes of Health (P01 CA055075, UM1 CA167552, U01 CA167552, R01 CA137178, R01 CA151993, and R35 CA197735), NHS by the National Institutes of Health (R01 CA137178, P01 CA087969, UM1 CA186107, R01 CA151993, and R35 CA197735) and PHS by the National Institutes of Health (R01 CA042182). Kentucky: This work was supported by the following grant support: Clinical Investigator Award from Damon Runyon Cancer Research Foundation (CI-8); NCI R01CA136726. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 509348, 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. MEC: National Institutes of Health (R37 CA54281, P01 CA033619, and R01 CA063464). MECC: This work was supported by the National Institutes of Health, U.S. Department of Health and Human Services (R01 CA81488 to SBG and GR). NFCCR: This work was supported by an Interdisciplinary Health Research Team award from the Canadian Institutes of Health Research (CRT 43821); the National Institutes of Health, U.S. Department of Health and Human Serivces (U01 CA74783); and National Cancer Institute of Canada grants (18223 and 18226). The authors wish to acknowledge the contribution of Alexandre Belisle and the genotyping team of the McGill University and Genome Quebec Innovation Centre, Montreal, Canada, for genotyping the Sequenom panel in the NFCCR samples. Funding was provided to Michael O. Woods by the Canadian Cancer Society Research Institute. OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research, and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Funding was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. SEARCH: The University of Cambridge has received salary support in respect of PDPP from the NHS in the East of England through the Clinical Academic Reserve. Cancer Research UK (C490/A16561); the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge. Swedish Mammography Cohort and Cohort of Swedish Men: This work is supported by the Swedish Research Council/Infrastructure grant, the Swedish Cancer Foundation, and the Karolinska Institute's Distinguished Professor Award to Alicja Wolk. VITAL: National Institutes of Health (K05 CA154337). WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN26 8201100003C, HHSN268201100004C, and HHS N27 1201100004C.SPAIN: Colorectal Cancer Genetics & Genomics, Spanish study was supported by Instituto de Salud Carlos III, co-funded by FEDER funds -a way to build Europe -(grants PI14-613 and PI09-1286), Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (grant 2017SGR723), and Junta de Castilla y Leon (grant LE22A10-2). Sample collection of this work was supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d'Oncologia de Catalunya (XBTC), Plataforma Biobancos PT13/0010/0013 and ICOBIOBANC, sponsored by the Catalan Institute of Oncology. PMH-SCCFR: National Institutes of Health (R01 CA076366 to P. Newcomb and U01 CA074794 to J. Potter).