title: HLA-DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma.
abstract: Increasing evidence suggests that HLA-DRB1 alleles reduce or increase the risk of developing ulcerative colitis-associated colorectal carcinoma (CRC) tumors. However, the role of HLA-DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA-DRB1 alleles are associated with IBD-independent CRC tumor. HLA-DRB1 allele polymorphisms were identified by sequence-based typing method in 53 CRC patients and 57 sex- and age-matched healthy Caucasian controls. Pearson's chi-squared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA-DRB1 in patients and controls. A total of 29 HLA-DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p = 0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p = 0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA-DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear.
authors.affiliation: CNR Institute of Translational Pharmacology, Rome and L'Aquila, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Aureli
authors.forename: Angelica
authors.initials: A
authors.lastname: Canossi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Del Beato
authors.forename: Luana
authors.initials: L
authors.lastname: Franceschilli
authors.forename: Oreste
authors.initials: O
authors.lastname: Buonomo
authors.forename: Franco
authors.initials: F
authors.lastname: Papola
authors.forename: Flavio
authors.initials: F
authors.lastname: De Sanctis
authors.forename: Giulia
authors.initials: G
authors.lastname: Lanzilli
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Sileri
authors.forename: Andrea
authors.initials: A
authors.lastname: Coppola
authors.forename: Sara
authors.initials: S
authors.lastname: Caratelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Arriga
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.forename: Piero
authors.initials: P
authors.lastname: Rossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sconocchia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D059811:HLA-DRB1 Chains
keywords: DRB1; HLA; HLA-DRB1*11:01; HLA-DRB1*13:01; PCR-SBT; colorectal cancer