Yuanjie Pang1, Jun Lv1,2, Christiana Kartsonaki3,4, Yu Guo5, Canqing Yu1,2, Yiping Chen3,4, Ling Yang3,4, Zheng Bian5, Iona Y Millwood3,4, Robin G Walters3,4, Xiaojun Li6, Ju Zou6, Michael V Holmes3,4,7, Junshi Chen8, Zhengming Chen3,4, Liming Li9,10. 1. Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China. 2. Peking University Center for Public Health and Epidemic Preparedness & Response (PKU-PHEPR), Peking University, 38 Xueyuan Road, Beijing, 100191, China. 3. Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford, UK. 4. Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK. 5. Chinese Academy of Medical Sciences, Beijing, China. 6. Jili Street Community Health Service Center, Liuyang, China. 7. National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, UK. 8. National Center for Food Safety Risk Assessment, Beijing, China. 9. Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China. lmleeph@vip.163.com. 10. Peking University Center for Public Health and Epidemic Preparedness & Response (PKU-PHEPR), Peking University, 38 Xueyuan Road, Beijing, 100191, China. lmleeph@vip.163.com.
Abstract
BACKGROUND: Gallstone disease (GSD) is associated with a higher risk of gastrointestinal (GI) cancer. However, it is unclear whether the associations are causal. METHODS: The prospective China Kadoorie Biobank (CKB) recorded 17,598 cases of GI cancer among 510,137 participants without cancer at baseline during 10 years of follow-up. Cox regression was used to estimate hazard ratios (HRs) for specific cancer by GSD status and duration. Mendelian randomisation was conducted to assess the genetic associations of GSD with specific cancer. RESULTS: Overall 6% of participants had symptomatic GSD at baseline. Compared with those without GSD, individuals with symptomatic GSD had adjusted HRs of 1.13 (1.01-1.29) for colorectal, 2.01 (1.78-2.26) for liver, 3.70 (2.88-4.87) for gallbladder, 2.31 (1.78-3.07) for biliary tract, and 1.38 (1.18-1.74) for pancreatic cancer. Compared with participants without GSD, the risks of colorectal, liver, gallbladder, biliary tract, and pancreatic cancer were highest during 0 to <5 years following disease diagnosis. There was evidence of genetic associations of GSD with these cancers, with odds ratios per 1-SD genetic score of 1.08 (1.05-1.11) for colorectal, 1.22 (1.19-1.25) for liver, 1.56 (1.49-1.64) for gallbladder, 1.39 (1.31-1.46) for biliary tract, and 1.16 (1.10-1.22) for pancreatic cancer. When meta-analysing the genetic estimates in CKB and UK Biobank, there was evidence of causal associations of GSD with colon cancer, gallbladder and biliary tract cancer (GBTC), and total GI cancer (RR per 1-SD: 1.05 [0.99-1.11], 2.00 [1.91-2.09], and 1.09 [1.05-1.13]). CONCLUSIONS: GSD was associated with higher risks of several GI cancers, warranting future studies on the underlying mechanisms.
BACKGROUND: Gallstone disease (GSD) is associated with a higher risk of gastrointestinal (GI) cancer. However, it is unclear whether the associations are causal. METHODS: The prospective China Kadoorie Biobank (CKB) recorded 17,598 cases of GI cancer among 510,137 participants without cancer at baseline during 10 years of follow-up. Cox regression was used to estimate hazard ratios (HRs) for specific cancer by GSD status and duration. Mendelian randomisation was conducted to assess the genetic associations of GSD with specific cancer. RESULTS: Overall 6% of participants had symptomatic GSD at baseline. Compared with those without GSD, individuals with symptomatic GSD had adjusted HRs of 1.13 (1.01-1.29) for colorectal, 2.01 (1.78-2.26) for liver, 3.70 (2.88-4.87) for gallbladder, 2.31 (1.78-3.07) for biliary tract, and 1.38 (1.18-1.74) for pancreatic cancer. Compared with participants without GSD, the risks of colorectal, liver, gallbladder, biliary tract, and pancreatic cancer were highest during 0 to <5 years following disease diagnosis. There was evidence of genetic associations of GSD with these cancers, with odds ratios per 1-SD genetic score of 1.08 (1.05-1.11) for colorectal, 1.22 (1.19-1.25) for liver, 1.56 (1.49-1.64) for gallbladder, 1.39 (1.31-1.46) for biliary tract, and 1.16 (1.10-1.22) for pancreatic cancer. When meta-analysing the genetic estimates in CKB and UK Biobank, there was evidence of causal associations of GSD with colon cancer, gallbladder and biliary tract cancer (GBTC), and total GI cancer (RR per 1-SD: 1.05 [0.99-1.11], 2.00 [1.91-2.09], and 1.09 [1.05-1.13]). CONCLUSIONS: GSD was associated with higher risks of several GI cancers, warranting future studies on the underlying mechanisms.
Authors: Frank Lammert; Kurinchi Gurusamy; Cynthia W Ko; Juan-Francisco Miquel; Nahum Méndez-Sánchez; Piero Portincasa; Karel J van Erpecum; Cees J van Laarhoven; David Q-H Wang Journal: Nat Rev Dis Primers Date: 2016-04-28 Impact factor: 52.329