Abstract
OBJECTIVE:
Female BRCA
(breast cancer gene)-1 and BRCA-2 mutations are significantly associated
with risk of developing breast and ovarian cancers, in turn, associated
with female infertility. BRCA-1 mutations have also been associated
with occult primary ovarian insufficiency (OPOI), as have different
mutations of the FMR1 gene. We, therefore,
hypothesized that FMR1
genotypes may be associated with menarcheal and menopausal ages of BRCA
mutation carriers.
PATIENTS:
We compared the FMR1
genotype and sub-genotype distribution in 99 BRCA1/2 positive women and
in 182 healthy women without a known history of familial breast and
ovarian cancer and searched for associations with age at menarche and
menopause. T-test was used to assess differences in menarcheal and
menopause ages, with times of menarche and menopause as continuous
variables.
RESULTS:
Women with BRCA1/2 mutations showed
significantly different FMR1 genotype and sub-genotype distributions
when compared with the control group (p<0.001). This result remained
stable in a sub-group analysis of
Caucasian BRCA1/2 carriers and healthy
controls (p<0.001).
In addition, BRCA1/2 carriers indicated a trend
toward shorter reproductive lifespan (p=0.18).
CONCLUSIONS:
Our
data confirm the previously reported highly skewed distribution of FMR1
genotypes and sub-genotypes toward a high preponderance of low FMR1
alleles in BRCA1/2 carriers. We could demonstrate that
BRCA-1 mutations
are associated with an
earlier onset of menopause compared to BRCA-2
carriers, although the distribution of the het-norm/low genotype is
similar in both groups. Our findings suggest that there may be other
factors beside the genotype that has an influence on menarche and
especially menopause age in BRCA mutation carriers.
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