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000170190 1001_ $$00000-0001-5184-2935$$aWang, Xiaoliang$$b0
000170190 245__ $$aAssociation Between Smoking and Molecular Subtypes of Colorectal Cancer.
000170190 260__ $$aOxford$$bOxford University Press$$c2021
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000170190 520__ $$aSmoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking.A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutation, KRAS mutation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. A multinomial logistic regression analysis was used to assess the association between smoking and risk of CRC subtypes by molecular characteristics, adjusting for age, sex, and study. All statistical tests were 2-sided and adjusted for Bonferroni correction.Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (P trend < .001). The associations differed statistically significantly between all molecular subtypes, which was the most statistically significant for CIMP and BRAF. Compared with never-smokers, smokers in the fourth quartile of pack-years had a 90% higher risk of CIMP-positive CRC (odds ratio = 1.90, 95% confidence interval = 1.60 to 2.26) but only 35% higher risk for CIMP-negative CRC (odds ratio = 1.35, 95% confidence interval = 1.22 to 1.49; P difference = 2.1 x 10-6). The association was also stronger in tumors that were CIMP positive, MSI high, or KRAS wild type when combined (P difference < .001).Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. Heavier smokers had particularly higher risk of CRC subtypes that were CIMP positive and MSI high in combination, suggesting that smoking may be involved in the development of colorectal tumors via the serrated pathway.
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000170190 7001_ $$0P:(DE-He78)6e02c183f41e45a5867dec393fb4616a$$aAmitay, Efrat$$b1$$udkfz
000170190 7001_ $$00000-0002-4173-7530$$aHarrison, Tabitha A$$b2
000170190 7001_ $$aBanbury, Barbara L$$b3
000170190 7001_ $$aBerndt, Sonja I$$b4
000170190 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b5$$udkfz
000170190 7001_ $$00000-0003-2225-6675$$aBuchanan, Daniel D$$b6
000170190 7001_ $$00000-0002-5549-2036$$aCampbell, Peter T$$b7
000170190 7001_ $$00000-0001-9835-7662$$aCao, Yin$$b8
000170190 7001_ $$aChan, Andrew T$$b9
000170190 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b10$$udkfz
000170190 7001_ $$aGallinger, Steven J$$b11
000170190 7001_ $$aGiannakis, Marios$$b12
000170190 7001_ $$aGiles, Graham G$$b13
000170190 7001_ $$00000-0001-5472-6761$$aGunter, Marc J$$b14
000170190 7001_ $$aHopper, John L$$b15
000170190 7001_ $$00000-0002-8964-6160$$aJenkins, Mark A$$b16
000170190 7001_ $$aLin, Yi$$b17
000170190 7001_ $$00000-0002-2818-5487$$aMoreno, Victor$$b18
000170190 7001_ $$aNishihara, Reiko$$b19
000170190 7001_ $$aNewcomb, Polly A$$b20
000170190 7001_ $$00000-0002-3909-2323$$aOgino, Shuji$$b21
000170190 7001_ $$aPhipps, Amanda I$$b22
000170190 7001_ $$00000-0002-0900-5735$$aSakoda, Lori C$$b23
000170190 7001_ $$00000-0001-7153-2766$$aSchoen, Robert E$$b24
000170190 7001_ $$aSlattery, Martha L$$b25
000170190 7001_ $$00000-0002-1324-0316$$aSong, Mingyang$$b26
000170190 7001_ $$00000-0002-6350-1107$$aSun, Wei$$b27
000170190 7001_ $$aThibodeau, Steven N$$b28
000170190 7001_ $$00000-0002-0271-1792$$aToland, Amanda E$$b29
000170190 7001_ $$aVan Guelpen, Bethany$$b30
000170190 7001_ $$00000-0001-8180-418X$$aWoods, Michael O$$b31
000170190 7001_ $$aHsu, Li$$b32
000170190 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b33$$udkfz
000170190 7001_ $$aPeters, Ulrike$$b34
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