Malinee PongsaveeVichanan YamkamonSumana DakengPornchai O-charoenratDuncan R. SmithGrady F. SaundersPimpicha PatmasiriwatMahidol University2018-09-132018-09-132009-06-01Genetic testing and molecular biomarkers. Vol.13, No.3 (2009), 307-317194502572-s2.0-67651021913https://repository.li.mahidol.ac.th/handle/20.500.14594/28052BACKGROUND: A significant proportion of familial and early-onset breast and ovarian cancers occur in individuals without coding mutations of BRCA1 and BRCA2. Aims: We identified genetic variation at 3'-untranslated region (UTR) of BRCA1 in familial and early-onset breast and ovarian cancer patients both with and without BRCA1/2 mutation in the coding regions (BRCA1/2 pos and BRCA1/2 neg), and verified the possible cancer risk factor of the specific 3'-UTR variation using functional analysis. METHODS: BRCA1 SNP analysis was screened in 46 patients and 103 unaffected Thais by heteroduplex analysis and DNA sequencing. After chi-square test for the potential cancer association of the specific 3'-UTR genotypes, the functional tests were conducted using several strategies of the luciferase gene expression model. RESULTS: We document the existence of two 3'-UTR polymorphic sites, the 5711+421(G or T) and the 5711+1286(C or T). Frequency of homozygous genotype 5711+421T/T_5711+1286T/T (or T/T-T/T) in the group of BRCA1/2 neg cancer patients was triple of that seen in unaffected persons and showed a significant cancer association (p = 0.007). Functional analysis of these polymorphic sites using luciferase experiments showed an obvious significant reduction in activity associated with the T allele at both sites. CONCLUSION: These results suggest that the inheritance of specific 3'-UTR polymorphisms may predispose individuals to early-onset or familial breast or ovarian cancer.Mahidol UniversityMedicineArticleSCOPUS10.1089/gtmb.2008.0127