title: Susceptibility genetic variants associated with early-onset colorectal cancer.
abstract: Colorectal cancer (CRC) is the second most common cancer in Western countries. Hereditary forms only correspond to 5% of CRC burden. Recently, genome-wide association studies have identified common low-penetrant CRC genetic susceptibility loci. Early-onset CRC (CRC<50 years old) is especially suggestive of hereditary predisposition although 85-90% of heritability still remains unidentified. CRC<50 patients (n = 191) were compared with a late-onset CRC group (CRC>65 years old) (n = 1264). CRC susceptibility variants at 8q23.3 (rs16892766), 8q24.21 (rs6983267), 10p14 (rs10795668), 11q23.1 (rs3802842), 15q13.3 (rs4779584), 18q21 (rs4939827), 14q22.2 (rs4444235), 16q22.1 (rs9929218), 19q13.1 (rs10411210) and 20p12.3 (rs961253) were genotyped in all DNA samples. A genotype-phenotype correlation with clinical and pathological characteristics in both groups was performed. Risk allele carriers for rs3802842 [Odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.1-2.05, P = 0.0096, dominant model) and rs4779584 (OR = 1.39, 95% CI 1.02-1.9, P = 0.0396, dominant model) were more frequent in the CRC<50 group, whereas homozygotes for rs10795668 risk allele were also more frequent in the early-onset CRC (P = 0.02, codominant model). Regarding early-onset cases, 14q22 (rs4444235), 11q23 (rs3802842) and 20p12 (rs961253) variants were more associated with family history of CRC or tumors of the Lynch syndrome spectrum excluding CRC. In our entire cohort, sum of risk alleles was significantly higher in patients with a CRC family history (OR = 1.40, 95% CI 1.06-1.85, P = 0.01). In conclusion, variants at 10p14 (rs10795668), 11q23.1 (rs3802842) and 15q13.3 (rs4779584) may have a predominant role in predisposition to early-onset CRC. Association of CRC susceptibility variants with some patient's familiar and personal features could be relevant for screening and surveillance strategies in this high-risk group and it should be explored in further studies.
authors.affiliation: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Villarroel 170, 08036 Barcelona, Catalonia, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Giráldez
authors.forename: Adriana
authors.initials: A
authors.lastname: López-Dóriga
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.forename: Anna
authors.initials: A
authors.lastname: Abulí
authors.forename: Xavier
authors.initials: X
authors.lastname: Bessa
authors.forename: Ceres
authors.initials: C
authors.lastname: Fernández-Rozadilla
authors.forename: Jenifer
authors.initials: J
authors.lastname: Muñoz
authors.forename: Miriam
authors.initials: M
authors.lastname: Cuatrecasas
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jover
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Xicola
authors.forename: Xavier
authors.initials: X
authors.lastname: Llor
authors.forename: Josep M
authors.initials: JM
authors.lastname: Piqué
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Clara
authors.initials: C
authors.lastname: Ruiz-Ponte
authors.forename: Angel
authors.initials: A
authors.lastname: Cosme
authors.forename: José María
authors.initials: JM
authors.lastname: Enríquez-Navascués
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Montserrat
authors.initials: M
authors.lastname: Andreu
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.forename: Francesc
authors.initials: F
authors.lastname: Balaguer
authors.forename: Sergi
authors.initials: S
authors.lastname: Castellví-Bel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors