© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 606-611, Copyright © 1998 by Oxford University Press
M Hisada, JE Garber, CY Fung, JF Fraumeni Jr and FP Li
BACKGROUND: Li-Fraumeni syndrome is a dominantly inherited disorder
characterized by early-onset breast cancer, sarcomas, and other cancers in
children and young adults. Members of families with this syndrome also
develop multiple primary cancers, but the frequency is unknown. To approach
this issue, we quantified the incidence of second and third primary cancers
in individuals from 24 Li-Fraumeni kindreds originally diagnosed with
cancer during the period from 1968 through 1986. METHODS: The relative risk
(RR) of subsequent cancers and 95% confidence intervals (CIs) were
calculated by use of population-based incidence data from the Connecticut
Cancer Registry. Kaplan-Meier analysis was used to determine the cumulative
probability (+/- standard error) of subsequent cancers. RESULTS: Among 200
Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%)
developed a second cancer. Eight individuals (4%) had a third cancer, while
four (2%) eventually developed a fourth cancer. Overall, the RR of
occurrence of a second cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative
probability of second cancer occurrence of 57% (+/- 10%) at 30 years after
diagnosis of a first cancer. RRs of second cancers occurring in families
with this syndrome were 83.0 (95% CI = 36.9-187.6), 9.7 (95% CI =
4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with a first cancer
at ages 0-19 years, 20-44 years, and 45 years or more, respectively. Thirty
(71%) of 42 subsequent cancers in this group were component cancers of
Li-Fraumeni syndrome. CONCLUSIONS: Compared with the general population,
members of Li-Fraumeni syndrome families have an exceptionally high risk of
developing multiple primary cancers. The excess risk of additional primary
cancers is mainly for cancers that are characteristic of Li-Fraumeni
syndrome, with the highest risk observed for survivors of childhood
cancers. Cancer survivors in these families should be closely monitored for
early manifestations of new cancers.
ARTICLES
Multiple primary cancers in families with Li-Fraumeni syndrome
Dana-Farber Cancer Institute, and Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
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