BACKGROUND: 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.
BACKGROUND: 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 cancerpatients 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 cancerpatients 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.
Authors: Cory Pelletier; William C Speed; Trupti Paranjape; Katie Keane; Rachel Blitzblau; Antoinette Hollestelle; Kyan Safavi; Ans van den Ouweland; Daniel Zelterman; Frank J Slack; Kenneth K Kidd; Joanne B Weidhaas Journal: Cell Cycle Date: 2011-01-01 Impact factor: 4.534
Authors: Lijun Zhu; Erich M Sturgis; Hua Zhang; Zhongming Lu; Ye Tao; Qingyi Wei; Guojun Li Journal: Int J Cancer Date: 2017-07-07 Impact factor: 7.396
Authors: X Chen; T Paranjape; C Stahlhut; T McVeigh; F Keane; S Nallur; N Miller; M Kerin; Y Deng; X Yao; H Zhao; J B Weidhaas; F J Slack Journal: Oncogene Date: 2014-06-09 Impact factor: 8.756
Authors: Jemima J Dorairaj; David W Salzman; Deirdre Wall; Tiffany Rounds; Carina Preskill; Catherine A W Sullivan; Robert Lindner; Catherine Curran; Kim Lezon-Geyda; Terri McVeigh; Lyndsay Harris; John Newell; Michael J Kerin; Marie Wood; Nicola Miller; Joanne B Weidhaas Journal: BMC Cancer Date: 2014-06-10 Impact factor: 4.430