RESUMO
BACKGROUND: The best known hereditary colorectal cancer syndromes, familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), constitute about 2% of all colorectal cancers, and there are at least as many non-FAP, non-HNPCC cases where the family history suggests a dominantly inherited colorectal cancer risk. Recently, a locus on chromosome 9q22.2-31.2 was identified by linkage analysis in sib pairs with colorectal cancer or adenoma. METHODS: Linkage analysis for the suggested locus on chromosome 9 was carried out in an extended Swedish family. This family had previously been investigated but following the identification of adenomas in several previously unaffected family members, these subjects were now considered to be gene carriers. RESULTS: In the present study, we found linkage of adenoma and colorectal cancer to chromosome 9q22.32-31.1 with a multipoint LOD score of 2.4. We were also able to define the region for this locus to 7.9 cM between the markers D9S280 and D9S277. CONCLUSIONS: Our result supports the presence of a susceptibility locus predisposing to adenoma and colorectal cancer in this chromosomal region.
Assuntos
Adenoma/genética , Cromossomos Humanos Par 9/genética , Neoplasias Colorretais/genética , Ligação Genética/genética , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Linhagem , SuéciaAssuntos
Pareamento Incorreto de Bases/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo do DNA/genética , Mutação/genética , Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte , Clonagem Molecular/métodos , DNA Complementar/genética , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Éxons/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Humanos , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/genética , Proteínas Nucleares , Proteínas Proto-Oncogênicas/genética , RNA/genética , Splicing de RNA/genética , RNA Circular , RNA Neoplásico/genética , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
Few studies have investigated the frequency of hereditary non-polyposis colorectal cancer (HNPCC) in patients with colorectal cancer (CRC), and these have shown marked geographic variations. The aim of this study was to estimate the frequency of HNPCC in a cohort of Uruguayan CRC patients. We included all patients operated consecutively for CRC in the Hospital Central de las Fuerzas Armadas (Uruguay) between 1987 and 2003. Cases were classified into three groups: (i) those fulfilling Amsterdam criteria; (ii) those not fulfilling Amsterdam criteria but considered as a population at increased risk of cancer; and (iii) sporadic CRC. Genetic analysis to detect point mutations in hMLH/hMSH2/hMSH6 genes was performed in group 1 patients. Cases not showing mutations were tested by multiplex ligation-dependent probe amplification. Among 461 patients, group 1 represented 2.6%, group 2 represented 5.6%, and sporadic cases 91.8%. hMLH1/hMSH2/hMSH6 mutations were found in 25% of cases classified as HNPCC (two in hMLH1 and one in hMSH2). No mutations were detected in hMSH6 gene. The proportion of CRC patients that fulfilled Amsterdam criteria agrees with other reports. However, the percentage of HNPCC cases with identified mutations (25%) may be lower than that reported from other populations. This may reflect, among other possible causes, a different genetic profile in the Uruguayan population.