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000168784 1001_ $$00000-0003-2114-2975$$aHua, Xinwei$$b0
000168784 245__ $$aGenetically predicted circulating C-reactive protein concentration and colorectal cancer survival: A Mendelian randomization consortium study.
000168784 260__ $$aPhiladelphia, Pa.$$bAACR$$c2021
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000168784 500__ $$a2021 Jul;30(7):1349-1358
000168784 520__ $$aA positive association between circulating C-reactive protein (CRP) and colorectal cancer (CRC) survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically-predicted CRP concentrations and CRC-specific survival.We used individual-level data for 16,918 eligible CRC cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Due to the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically-predicted CRP concentrations and CRC-specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components.Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to CRC. Genetically-predicted CRP concentration was not associated with CRC-specific survival (HD= -1.15, 95% CI: -2.76 to 0.47 per 100,000 person-years, P =0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location.Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on CRC-specific survival.Future research evaluating genetically-determined levels of other circulating inflammatory biomarkers (i.e. interleukin-6) with CRC survival outcomes is needed.
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000168784 7001_ $$aDai, James Y$$b1
000168784 7001_ $$aLindström, Sara$$b2
000168784 7001_ $$00000-0002-4173-7530$$aHarrison, Tabitha A$$b3
000168784 7001_ $$aLin, Yi$$b4
000168784 7001_ $$aAlberts, Steven R$$b5
000168784 7001_ $$0P:(DE-He78)9b2a61b2abe4a64ca23b6783b7c4fe63$$aAlwers, Elizabeth$$b6$$udkfz
000168784 7001_ $$aBerndt, Sonja I$$b7
000168784 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b8$$udkfz
000168784 7001_ $$00000-0003-2225-6675$$aBuchanan, Daniel D$$b9
000168784 7001_ $$00000-0002-5549-2036$$aCampbell, Peter T$$b10
000168784 7001_ $$aCasey, Graham$$b11
000168784 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b12$$udkfz
000168784 7001_ $$aGallinger, Steven$$b13
000168784 7001_ $$00000-0003-4946-9099$$aGiles, Graham G$$b14
000168784 7001_ $$00000-0003-0308-8223$$aGoldberg, Richard M$$b15
000168784 7001_ $$aGunter, Marc J$$b16
000168784 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b17$$udkfz
000168784 7001_ $$aJenkins, Mark A$$b18
000168784 7001_ $$aJoshi, Amit D$$b19
000168784 7001_ $$aMa, Wenjie$$b20
000168784 7001_ $$00000-0001-5764-7268$$aMilne, Roger L$$b21
000168784 7001_ $$aMurphy, Neil$$b22
000168784 7001_ $$00000-0002-2692-221X$$aPai, Rish K$$b23
000168784 7001_ $$00000-0002-0900-5735$$aSakoda, Lori C$$b24
000168784 7001_ $$00000-0001-7153-2766$$aSchoen, Robert E$$b25
000168784 7001_ $$aShi, Qian$$b26
000168784 7001_ $$00000-0002-1655-6543$$aSlattery, Martha L$$b27
000168784 7001_ $$aSong, Mingyang$$b28
000168784 7001_ $$aWhite, Emily$$b29
000168784 7001_ $$aLe Marchand, Loic$$b30
000168784 7001_ $$aChan, Andrew T$$b31
000168784 7001_ $$00000-0001-5666-9318$$aPeters, Ulrike$$b32
000168784 7001_ $$aNewcomb, Polly A$$b33
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