Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT
| Autor: | Larson, G. P., Ding, Y., Cheng, L. S. -C, Lundberg, C., Gagalang, V., Rivas, G., Geller, L., Jeffrey Weitzel, Macdonald, D., Archambeau, J., Slater, J., Neuberg, D., Daly, M. B., Angel, I., Benson Iii, A. B., Smith, K., Kirkwood, J. M., O Dwyer, P. J., Raskay, B., Sutphen, R., Drew, R., Stewart, J. A., Werndli, J., Johnson, D., Ruckdeschel, J. C., Elston, R. C., Krontiris, T. G. |
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| Předmět: |
Adult
Aged 80 and over Male Cancer Research Genetic Linkage Chromosome Mapping Prostatic Neoplasms Adenocarcinoma Middle Aged Polymorphism Single Nucleotide Acid Anhydride Hydrolases Neoplasm Proteins Haplotypes Oncology Case-Control Studies Humans Genetic Predisposition to Disease Chromosomes Human Pair 3 Aged Microsatellite Repeats |
| Zdroj: | Scopus-Elsevier |
| Popis: | We conducted linkage analysis of 80 candidate genes in 201 brother pairs affected with prostatic adenocarcinoma. Markers representing two adjacent candidate genes on chromosome 3p, CDC25A and FHIT, showed suggestive evidence for linkage with single-point identity-by-descent allele-sharing statistics. Fine-structure multipoint linkage analysis yielded a maximum LOD score of 3.17 (P = 0.00007) at D3S1234 within FHIT intron 5. For a subgroup of 38 families in which three or more affected brothers were reported, the LOD score was 3.83 (P = 0.00001). Further analysis reported herein suggested a recessive mode of inheritance. Association testing of 16 single nucleotide polymorphisms (SNP) spanning a 381-kb interval surrounding D3S1234 in 202 cases of European descent with 143 matched, unrelated controls revealed significant evidence for association between case status and the A allele of single nucleotide polymorphism rs760317, located within intron 5 of FHIT (Pearson's χ2 = 8.54, df = 1, P = 0.0035). Our results strongly suggest involvement of germline variations of FHIT in prostate cancer risk. |
| Databáze: | OpenAIRE |
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