title: Colorectal cancer and polymorphisms in DNA repair genes WRN, RMI1 and BLM.
abstract: RecQ helicase family members are involved in multiple DNA repair pathways, protecting the genome from incorrect recombination during mitosis and maintaining its stability. Deficiencies in genes encoding the RecQ helicases WRN and BLM lead to rare autosomal recessive diseases, Werner and Bloom syndromes, which have been implicated in early onset of aging, and predisposition to various types of cancer. We investigated associations of WRN, BLM and BLM-associated protein (BLAP75/RMI1) gene polymorphisms and risk of colorectal cancer (CRC), genotyping WRN V114I (rs2230009), WRN L1074F (rs2725362), WRN C1367R (rs1346044), RMI1 S455N (rs1982151) and BLM P868L (rs11852361). A large population-based case-control study, including 1795 CRC cases and 1805 controls, found no evidence for an association between the selected allelic variants in DNA repair-related genes and CRC risk. However, we detected a significant association of BLM P868L with an increased rectal cancer risk (odds ratio = 1.29, 95% confidence interval 1.02-1.64 and P = 0.04), suggesting a potential cancer-site specificity. This is the first study to analyze the associations between polymorphisms in WRN, BLM and RMI1 and CRC risk. Although none of them showed a significant association with CRC, the association of BLM P868L with rectal cancer risk requires further investigation.
authors: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, 69115 Heidelberg, Germany. b.frank@dkfz.de
authors: Bernd
authors: B
authors: Frank
authors: Michael
authors: M
authors: Hoffmeister
authors: Norman
authors: N
authors: Klopp
authors: Thomas
authors: T
authors: Illig
authors: Jenny
authors: J
authors: Chang-Claude
authors: Hermann
authors: H
authors: Brenner
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D053484:RecQ Helicases / Q000235:genetics*; D012306:Risk; D000071657:Werner Syndrome Helicase
chemical_list: D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C501527:RMI1 protein, human; D005090:Exodeoxyribonucleases; C097151:Bloom syndrome protein; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase