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000144081 1001_ $$00000-0001-9571-4257$$aPardini, Barbara$$b0
000144081 245__ $$aDNA repair and cancer in colon and rectum: novel players in genetic susceptibility.
000144081 260__ $$aBognor Regis$$bWiley-Liss$$c2020
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000144081 520__ $$aInter-individual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value=3.5x10-6 ) and rs2189517 (in RAD51B) with rectal cancer risk (p-value=5.7x10-6 ). The results had statistical significance close to the Bonferroni corrected p-value of 5.8x10-6 . Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g. rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis. This article is protected by copyright. All rights reserved.
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000144081 7001_ $$aCorrado, Alda$$b1
000144081 7001_ $$aPaolicchi, Elisa$$b2
000144081 7001_ $$aCugliari, Giovanni$$b3
000144081 7001_ $$aBerndt, Sonja I$$b4
000144081 7001_ $$aBezieau, Stephane$$b5
000144081 7001_ $$aBien, Stephanie A$$b6
000144081 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b7$$udkfz
000144081 7001_ $$aCaan, Bette J$$b8
000144081 7001_ $$aCampbell, Peter T$$b9
000144081 7001_ $$aCasey, Graham$$b10
000144081 7001_ $$aChan, Andrew T$$b11
000144081 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b12$$udkfz
000144081 7001_ $$aCotterchio, Michelle$$b13
000144081 7001_ $$aGala, Manish$$b14
000144081 7001_ $$aGallinger, Steven J$$b15
000144081 7001_ $$aHaile, Robert W$$b16
000144081 7001_ $$aHarrison, Tabitha A$$b17
000144081 7001_ $$aHayes, Richard B$$b18
000144081 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b19$$udkfz
000144081 7001_ $$aHopper, John L$$b20
000144081 7001_ $$aHsu, Li$$b21
000144081 7001_ $$aHuyghe, Jeroen$$b22
000144081 7001_ $$aJenkins, Mark A$$b23
000144081 7001_ $$aLe Marchand, Loic$$b24
000144081 7001_ $$aLin, Yi$$b25
000144081 7001_ $$aLindor, Noralane M$$b26
000144081 7001_ $$aNan, Hongmei$$b27
000144081 7001_ $$aNewcomb, Polly A$$b28
000144081 7001_ $$aOgino, Shuji$$b29
000144081 7001_ $$aPotter, John D$$b30
000144081 7001_ $$aSchoen, Robert E$$b31
000144081 7001_ $$00000-0002-1655-6543$$aSlattery, Martha L$$b32
000144081 7001_ $$aWhite, Emily$$b33
000144081 7001_ $$aVodickova, Ludmila$$b34
000144081 7001_ $$aVymetalkova, Veronika$$b35
000144081 7001_ $$aVodicka, Pavel$$b36
000144081 7001_ $$aGemignani, Federica$$b37
000144081 7001_ $$aPeters, Ulrike$$b38
000144081 7001_ $$aNaccarati, Alessio$$b39
000144081 7001_ $$aLandi, Stefano$$b40
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