Prevalence of 185delAG and 5382insC mutations in BRCA1, and 6174delT in BRCA2 in women of Ashkenazi Jewish origin in southern Brazil

Abstract

Certain mutations in BRCA1 and BRCA2 genes are frequent in the Ashkenazi Jewish population. Several factors contribute to this increased frequency, including consanguineous marriages and an event known as a “bottleneck”, which occurred in the past and caused a drastic reduction in the genetic variability of this population. Several studies were performed over the years in an attempt to elucidate the role of BRCA1 and BRCA2 genes in susceptibility to breast cancer. The aim of this study was to estimate the carrier frequency of certain common mutations in the BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) genes in an Ashkenazi Jewish population from Porto Alegre, Brazil. Molecular analyses were done by PCR followed by RFLP (ACRS). The carrier frequencies for BRCA1 185delAG and 5382insC were 0.78 and 0 respectively, and 0.4 for the BRCA2 6174deT mutation. These findings are similar to those of some prior studies but differ from others, possibly due to excluding individuals with a personal or family history of cancer. Our sample was drawn from the community group and included individuals with or without a family or personal history of cancer. Furthermore, increased dispersion among Ashkenazi subpopulations may be the result of strong genetic drift and/or admixture. It is therefore necessary to consider the effects of local admixture on the mismatch distributions of various Jewish populations.

Hereditary breast and ovarian cancer susceptibility genes (Review)

“…Ashkenazi Jewish subjects are observed at increased frequency compared to other Caucasian, because this population harbors ancient BRCA1 and BRCA2 mutant alleles. Mutation analysis revealed the c. 5266dup (until recently referred in the literature as 5382insC), c. 68_69del (185delAG) and 4153delA mutations in BRCA1 and c. 5946del (6174delT) mutation in BRCA2 (13). BRCA gene founder mutations such as BRCA1c.…”

Relationship of Breast Cancer with Ovarian Cancer

“…The most common susceptibility genes in this field are BRCA1/ BRCA2. If any mutations are present in either of these genes, it translates to a 60-85% lifetime risk of developing breast or ovarian cancer [4].…”

“…Frequency of this mutation is higher than in the rest of the Caucasian population, because the female Ashkenazi Jewish population harbors ancient BRCA1 / BRCA 2 mutant alleles. The 5266dup, BRCA2999del5 and BRCA1delexon17 mutations have been defined in some populations such as Slavic, Finnish, Icelandic and German [4].…”

Mutacja BRCA1 4153delA („bałtycko-czarnomorska”) u chorych na raka piersi na Ukrainie

“…W odniesieniu do RP -w rodzinach 36 spośród 335 (10,7%) pacjentów obserwowano 51 przypadków RP (w 28 -po jednym, u 10 -po dwa, zaś u jednej pacjentki -w trzech przypadkach -za wyjątkiem jej samej). Wśród krewnych pacjentów były: matki (u 9 chorych), siostry (9) i córki (3), babki (6, w tym u 5 -po linii matki), ciotki (17, w tym u 13 -po linii matki), dalecy krewni (7).…”

“…"Efekt założyciela" w raku piersi znaleziono w etnicznej grupie Żydów aszkenazyjskich. Pierwsze badanie przepro-wadzono w USA [4], a później wśród Żydów aszkenazyjskich w Izraelu [5], Australii [6], w Ameryce Południowej [7] i w niektórych krajach europejskich [8].…”