title: The EGFR R521K polymorphism influences the risk to develop colorectal cancer.
abstract: Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been extensively investigated for its possible involvement in cancer development and progression. In colorectal cancer (CRC) EGFR family has been found frequently over-expressed, thus therapy targeting EGFR has been developed. Interestingly, it has been observed that genetic variants in these receptors may alter the therapeutic efficacy of EGFR inhibitors. Polymorphic variants in members of the EGFR family could influence different biologic activities, such as ligands affinity, dimerization efficiency, kinase activity, expression levels, with a consequent impact in signalling pathways and cell behaviour. This study aimed to verify whether single nucleotide polymorphisms (SNPs) of EGFR family members could represent susceptibility factors able to influence the risk to develop CRC. Peripheral blood of 70 Italian colon cancer patients and 72 healthy controls was used as a source of genomic DNA to investigate EGFR, HER2 and HER3 common non-synonymous SNPs. Genetic association tests were performed to verify a possible relationship with CRC. Evidence of genotype association was found for the R521K EGFR polymorphism under a dominant mode of inheritance (Mid-P=0.031). Genotypes with the variant allele of EGFR R521K SNP confer a risk reduction to develop CRC.
authors: Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Italy.
authors: Marcella
authors: M
authors: Martinelli
authors: Giampaolo
authors: G
authors: Ugolini
authors: Luca
authors: L
authors: Scapoli
authors: Stefano
authors: S
authors: Rivetti
authors: Mattia
authors: M
authors: Lauriola
authors: Gabriella
authors: G
authors: Mattei
authors: Giancarlo
authors: G
authors: Rosati
authors: Isacco
authors: I
authors: Montroni
authors: Alessio
authors: A
authors: Manaresi
authors: Davide
authors: D
authors: Zattoni
authors: Mario
authors: M
authors: Taffurelli
authors: Rossella
authors: R
authors: Solmi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008239:Lysine / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D001120:Arginine; C512478:EGFR protein, human; D066246:ErbB Receptors; D008239:Lysine