The FMR1 CGG repeat test is not a candidate prescreening tool for identifying women with a high probability of being carriers of BRCA mutations.
The identification of women with a high probability of being carriers of pathogenic BRCA mutation is not straightforward and a major improvement would be the availability of markers of mutations that could be directly evaluated in individuals asking for genetic testing. The FMR1 gene testing was recently proposed as a candidate prescreening tool because an association between BRCA pathogenic mutations and FMR1 genotypes with 'low alleles' (CGG repeat number <26) was observed. To confirm this hypothesis, we evaluated the distribution of FMR1 alleles and genotypes between BRCA mutation carriers and non-carriers in a cohort of 147 Italian women, free of cancer or affected by breast and/or ovarian cancer, who were tested for the presence of BRCA mutation in a clinical setting. The distribution of FMR1 CGG repeat numbers in the two groups was similar (lower allele median/mean were 30/27.4 and 30/27.9, respectively; Mann-Whitney test P=0.997) and no difference in the FMR1 genotype distribution was present (χ(2)=0.503, d.f.=2, P=0.78). This result is in contrast with literature data and suggests that FMR1 genetic testing is not a candidate BRCA prescreening tool.
Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy.
Maria Teresa
MT
Ricci
Laboratory of Human Genetics, Galliera Hospital, Genoa, Italy.
Loredana
L
Pennese
Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy.
Viviana
V
Gismondi
Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy.
Chiara
C
Perfumo
Laboratory of Human Genetics, Galliera Hospital, Genoa, Italy.
Marina
M
Grasso
Laboratory of Human Genetics, Galliera Hospital, Genoa, Italy.
Elena
E
Gennaro
Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genoa, Italy.
Paolo
P
Bruzzi
Unit of Hereditary Cancer, IRCCS AOU San Martino-IST, Genoa, Italy.
Liliana
0000000348716668
L
Varesco
D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006580:Genetic Carrier Screening; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D018911:Trinucleotide Repeats
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; C492913:BRCA1 protein, human; C551750:BRCA2 protein, human; C497683:FMR1 protein, human