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BMJ 2008; 336 doi: (Published 03 January 2008) Cite this as: BMJ 2008;336:16

Take care with p53

The protein p53—so called because it is a phosphoprotein with a molecular mass of 53 kD—could be one of the most important molecules in biology, writes an expert in cancer genetics (p 2539). p53 helps control angiogenesis, apoptosis, and cell cycling, DNA repair, and regulation of oxidative stress, all of which are key processes in the growth and development of cancers. Abnormalities in TP53—the gene that encodes p53—are common in many cancers and are often associated with prognosis. In one recent study, disruptive mutations of TP53 within squamous cell cancers of the head and neck were associated with significantly shorter survival (hazard ratio for death 1.7, 95% CI 1.2 to 2.4).

Exploiting what we already know about this protein and its gene won’t be easy. The functions of p53 are so diverse that manipulating them—with gene therapy, for example—could have widespread and unpredictable effects. Overexpression of TP53 causes premature ageing in mice, while at least one polymorphism is associated with longer life in humans, despite a small increase in the risk of cancer. p53 seems to be “master and commander” of the cellular processes that control growth, life, and death. We should be careful what we do with it.

One vertebral fracture leads to another, for at least 15 years

Once a woman reaches 65, her absolute risk of a vertebral fracture depends firstly on whether or not she already has one and secondly on her bone mineral density (BMD). In the longest cohort study so far, women with a previous fracture and established osteoporosis had a greater than 50% chance of a new vertebral fracture over the next 15 years, compared with less than 10% for women with neither. The two risk factors operated independently of each other.

History of fracture was a better …

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