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000143174 1001_ $$aWang, Xiaoliang$$b0
000143174 245__ $$aMendelian randomization analysis of C-reactive protein on colorectal cancer risk.
000143174 260__ $$aOxford$$bOxford Univ. Press$$c2019
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000143174 520__ $$aChronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach.Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk.Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors.In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.
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000143174 7001_ $$aDai, James Y$$b1
000143174 7001_ $$aAlbanes, Demetrius$$b2
000143174 7001_ $$0P:(DE-He78)d023fdf423d87ee6c710e34dd7581fa0$$aArndt, Volker$$b3$$udkfz
000143174 7001_ $$aBerndt, Sonja I$$b4
000143174 7001_ $$aBézieau, Stéphane$$b5
000143174 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b6$$udkfz
000143174 7001_ $$aBuchanan, Daniel D$$b7
000143174 7001_ $$0P:(DE-He78)7ca7eafba864e5c3ebb7598149380452$$aButterbach, Katja$$b8$$udkfz
000143174 7001_ $$aCaan, Bette$$b9
000143174 7001_ $$aCasey, Graham$$b10
000143174 7001_ $$aCampbell, Peter T$$b11
000143174 7001_ $$aChan, Andrew T$$b12
000143174 7001_ $$aChen, Zhengyi$$b13
000143174 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b14$$udkfz
000143174 7001_ $$aCotterchio, Michelle$$b15
000143174 7001_ $$aEaston, Douglas F$$b16
000143174 7001_ $$aGiles, Graham G$$b17
000143174 7001_ $$aGiovannucci, Edward$$b18
000143174 7001_ $$aGrady, William M$$b19
000143174 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b20$$udkfz
000143174 7001_ $$aHopper, John L$$b21
000143174 7001_ $$aHsu, Li$$b22
000143174 7001_ $$aJenkins, Mark A$$b23
000143174 7001_ $$aJoshi, Amit D$$b24
000143174 7001_ $$aLampe, Johanna W$$b25
000143174 7001_ $$aLarsson, Susanna C$$b26
000143174 7001_ $$aLejbkowicz, Flavio$$b27
000143174 7001_ $$aLi, Li$$b28
000143174 7001_ $$aLindblom, Annika$$b29
000143174 7001_ $$aLe Marchand, Loic$$b30
000143174 7001_ $$aMartin, Vicente$$b31
000143174 7001_ $$aMilne, Roger L$$b32
000143174 7001_ $$aMoreno, Victor$$b33
000143174 7001_ $$aNewcomb, Polly A$$b34
000143174 7001_ $$aOffitt, Kenneth$$b35
000143174 7001_ $$aOgino, Shuji$$b36
000143174 7001_ $$aPharoah, Paul D P$$b37
000143174 7001_ $$aPinchev, Mila$$b38
000143174 7001_ $$aPotter, John D$$b39
000143174 7001_ $$aRennert, Hedy S$$b40
000143174 7001_ $$aRennert, Gad$$b41
000143174 7001_ $$aSaliba, Walid$$b42
000143174 7001_ $$aSchafmayer, Clemens$$b43
000143174 7001_ $$aSchoen, Robert E$$b44
000143174 7001_ $$0P:(DE-He78)01ef71f71b01a3ec3b698653fd43fe86$$aSchrotz-King, Petra$$b45$$udkfz
000143174 7001_ $$aSlattery, Martha L$$b46
000143174 7001_ $$aSong, Mingyang$$b47
000143174 7001_ $$aStegmaier, Christa$$b48
000143174 7001_ $$aWeinstein, Stephanie J$$b49
000143174 7001_ $$aWolk, Alicja$$b50
000143174 7001_ $$aWoods, Michael O$$b51
000143174 7001_ $$aWu, Anna H$$b52
000143174 7001_ $$aGruber, Stephen B$$b53
000143174 7001_ $$aPeters, Ulrike$$b54
000143174 7001_ $$aWhite, Emily$$b55
000143174 773__ $$0PERI:(DE-600)1494592-7$$a10.1093/ije/dyy244$$n3$$p767-780$$tInternational journal of epidemiology$$v48$$x1464-3685$$y2019
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