Permanent replacement of joints damaged by fracture or arthritis has b
ecome common over the last 50 years. Vigilance over possible long-term
adverse effects of metal prostheses is required. Some of the metal co
mponents are potentially carcinogenic. Prolonged contact of metal allo
ys with body fluids results in gradual corrosion of even the most iner
t metals. Three cohost studies of persons with a hip prosthesis have b
een reported; they provide direct, quantitative observations of cancer
risk in a human population with hip prosthesis. The design and the re
sults of these studies are similar. Combining the results sharpens the
precision of risk estimates. Collectively, the studies examined cance
r risk in 40,945 patients followed up for a mean 8.5 years after hip r
eplacement. Overall, the relative risk of cancer was 1.02 (95 percent
CI 1.00 to 1.05). There was an 8 percent excess of haemopoietic malign
ancy (leukaemia and lymphoma), with a total of 347 cases observed (RR
1.08, 95 percent CI 0.97 to 1.20). Significant deficits of cancers of
the breast and large bowel were seen in the two smaller studies, but c
ombined results from all three studies suggest the relative risk is cl
ose to unity. Cancer risk in the first 10 years after hip replacement
was not different from that expected, but there was an excess of borde
rline statistical significance 10 or more years after surgery, with a
relative risk of 1.08 (95 percent CI 1.00 to 1.13) based on 1,005 case
s. All three studies were well-designed and executed. Their results ar
e not alarming, but give no cause for complacency, since the number of
patients with a prosthesis and the length of time they live with the
prosthesis will increase. A register of malignancy complicating joint
prosthesis would not help quantify any risk. Instead, a large cohort s
tudy of patients with joint prostheses is needed, including informatio
n on the type and composition of the prosthesis and on potential confo
unding exposures for each patient. Measures of corrosion in cancer cas
es and of tissue levels of relevant metal ions in cases and controls (
prosthesis but no cancer) matched for age, sex, and time since inserti
on would be valuable. Such a study could be done internationally, usin
g orthopedic units with good clinical records for 10 to 15 years in ar
eas with long-term cancer registration.