p53 has a critical role in cell-cycle control. As such, it has been identified as an important target in human carcinogenesis. However, since human p53 was cloned, >/=10 DNA-sequence polymorphisms have been identified (Matlashewski et al. 1987; Weston and Godbold 1997). The codon 72 polymorphism (arginine/proline: G/C), the first to be described, has been the subject of 31 epidemiological case-control studies that have explored a potential association with cancer (Olschwang et al. 1991; Weston et al. 1992, 1994, 1997; Zhang et al. 1992; Kawajiri et al. 1993; Birgander et al. 1995, 1996b; Jin et al. 1995; Själander et al. 1995a, 1996a; Wu et al. 1995; Murata et al. 1996; To-Figueras et al. 1996; Golovleva et al. 1997; Weston and Godbold 1997; Yung et al. 1997; Hayes et al. 1998; Helland et al. 1998; Hildesheim et al. 1998; Josefsson et al. 1998; Lanham et al. 1998; Minaguchi et al. 1998; Rosenthal et al. 1998; Storey et al. 1998; Tagawa et al. 1998; Wang-Gohrke et al. 1998). Although they err on the side of caution by citing Weston and Godbold (1997), Bonafè et al. (1999, p. 293), referring to the codon 72 polymorphism, state that "overall, the available data in the literature suggest that p53 variants may be considered as risk factors for some of the major neoplastic diseases in humans, such as lung, colorectal, breast and cervical cancer and are expected to affect survival." With respect to codon 72, we contend that this is probably not the case. In the available data, lung cancer is the subject of eight studies (Weston et al. 1992, 1994; Kawajiri et al. 1993; Birgander et al. 1995; Jin et al. 1995; Murata et al. 1996; To-Figueras et al. 1996; Tagawa et al. 1998). Three studies claim a statistically significant association: in one study, a subset analysis suggested a relationship in lung cancer cases diagnosed at age <53 years (Jin et al. 1995); in the other two, the allelic frequencies were almost identical (and the difference was not significant) between cases and controls (Kawajiri et al.  observed a proline-allele frequency of .35 for controls and .36 for cases [n = 347 and 328, respectively]). Murata et al. (1996) observed a proline-allele frequency of .40 for controls and .35 for cases (n = 152 and 191, respectively), but associations of cancer risk were claimed on the basis of higher numbers of homozygotes (Kawajiri et al. 1993; Murata et al. 1996). One study (Kawajiri et al. 1993) implicated proline; the other (Murata et al. 1996), arginine.
Dr. Ainsley Weston, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, Morgantown, WV 26505-2888