How Can Birthweight Impact Osteosarcoma Risk in Later Life?
DrBudWiederman, MD, MA, Evidence eMended Editor, Grand Rounds
This is a classic case control study in that it demonstrates both the strengths and
weaknesses of this study design. I was also intrigued with how prenatal factors could
possibly influence a cancer that tends to strike adolescents.
Researchers used California Department of Public Health (CDPH) vital statistics to
find 670 patients with osteosarcoma and 2860 control children matched for sex, birth
year, and race/ethnicity. Their final analysis showed that higher birthweight was
associated with more advanced stage of osteosarcoma as well as greater tumor extension
into surrounding tissues and likelihood of distant metastases at the time of diagnosis.
Further quantification showed a 1.11-fold increase in the odds of having metastatic
disease with each 200 g increase in birthweight.
This is a perfect scenario for a case control study. Osteosarcoma is a fairly uncommon
event, only 400 children are diagnosed per year in the United States, so it would
be difficult to perform prospective population-based studies. The investigators chose
to have 4 control children for each osteosarcoma case, a fairly hefty number. Their
analysis is accurate, but of course the data are shaky because of the problems inherent
in any case control study. The number of variables available for analysis was limited
by what was collected by the CDPH, and the authors also commented that this data could
have problems with accuracy.
Another limitation is unique to the biology of this question, and the authors did
a good job explaining this. Key to any hypothesis for an association of a disease
with particular risk factors is whether the association is biologically plausible.
Stated differently, does it make sense based on current understanding of disease pathogenesis
that the risk factor (birthweight) could have some bearing on development or severity
of disease (osteosarcoma)? In this example, it has been proposed that the connection
is insulin-like growth factors (IGFs). Higher birthweight infants may have increased
IGF exposure in utero, and IGF also has been shown to act as an in vivo osteoblast chemotactic factor and in vitro mitogen for osteosarcoma growth. The authors note, however, that birthweight is affected
by a number of other factors, such as maternal conditions and parental height and
weight, and as such is a crude measurement that may mask effects of more significant
risk factors. Unfortunately, the CDPH data did not track those other conditions.
So, this case control study mostly points to potential mechanisms for osteosarcoma
presentations later in life, which in turn could lead to investigations of pathogenesis
that ultimately could be targeted for prevention and treatment of this serious disease.