Invasive breast carcinoma - IARC

cient power to determine the effect in
B R C A 2 carriers alone. Similarly, the variant
pro g e s t e rone receptor allele named
PROGINS was associated with an odds
ratio of 2.4 for ovarian cancer among
214 B R C A 1 / 2 carriers with no past
e x p o s u re to oral contraceptives, comp
a red to women without ovarian cancer
and with no PROGINS allele {2487}. A
C/G polymorphism in the 5' untranslated
region of R A D 5 1 was found to modify
both breast and ovarian cancer risk in
carriers of B R C A 2 {1644,3053}. These
results support the hypothesis that
genetic variation in the genes constituting
endocrine signalling and DNA re p a i r
pathways may modify B R C A 2- a s s o c i a t-
ed cancer risk.
Hormonal risk modifiers
As in the BRCA1 syndrome, the breast
cancer risk of BRCA2 carriers is influenced
by hormonal factors, including
oral contraceptives and pregnancy (see
page 56).
Prognosis and prevention
Life expectancy and preventive strategies
are similar to those discussed for
BRCA1 carriers (see page 56).
Li-Fraumeni syndrome
P. Hainaut
R. Eeles
H. Ohgaki
M. Olivier
Definition
Li-Fraumeni syndrome (LFS) is an
inherited neoplastic disease with autosomal
dominant trait. It is characterized
by multiple primary neoplasms in
c h i l d ren and young adults, with a predominance
of soft tissue sarc o m a s ,
o s t e o s a rcomas, breast cancer, and an
i n c reased incidence of brain tumours,
leukaemia and adre n o c o rtical carc i n o-
ma. The majority of Li-Fraumeni cases
is caused by a T P 5 3 g e rmline mutat
i o n .
MIM Nos. {1835}
Li-Fraumeni syndrome 151623
TP53 mutations
(germline and sporadic) 191170
CHEK2 mutations 604373
Synonym
S a rcoma family syndrome of Li and
Fraumeni.
Incidence
F rom 1990 to 1998, 143 families with a
T P 5 3 g e rmline mutations were re p o rted
{2086}. The IARC Database { w w w.
i a rc . f r / p 5 3 / g e rmline.html} c u r rently contains
223 families {2104a}.
Diagnostic criteria
The criteria used to identify an affected
individual in a Li-Fraumeni family are: (i)
occurrence of sarcoma before the age of
45 and (ii) at least one first degree relative
with any tumour before age 45 and
(iii) a second (or first) degree relative
with cancer before age 45 or a sarcoma
at any age {273,957,1650}.
A
Fig. 8.11 A A fraction of tumours in families with a TP53 germline mutation. B Mean age of patients with tumours caused by a TP53 germline mutation, according
to organ site.
B
BRCA2 syndrome / Li-Fraumeni syndrome 351