---

In Caucasian GSEC males, the GSTT1 gene deletions were less prevalent than in females. Among the octogenarians, we could not demonstrate a significant gender difference for the sequence variations under study. Octogenarians had slightly less frequent GSTT1 deletions than nonagenarians, and GSTM1 gene deletions were marginally more prevalent. This is in contrast to the results of an Italian study of polymorphisms of metabolic enzymes in healthy nonagenarians and centenarians, where GSTT1 deletions were significantly more prevalent than in the younger reference group (28% versus 19%), and no association with longevity could be demonstrated for the GSTM1 deletion and for CYP1A1 polymorphisms (Taioli et al., 2001).

---

A pronounced pattern of allelic differences could be shown for octogenarians with and without a diagnosis of cancer during lifetime with respect to the genetic polymorphisms under study, but random variation due to small numbers of subjects and due to the large number of comparisons has to be taken into account. A significant deviation from Hardy-Weinberg equilibrium could be demonstrated for GSTP1 I105V, with fewer observed heterozygous 105IV genotypes and more homozygous 105VV genotypes than expected among non-cancer octogenarians. Like CYP1B1, GSTP1 has a corresponding rationale for an association with age-related effects. The GSTP1 I105V sequence variation is located at the substrate binding site of the enzyme and has been shown to affect enzyme activity (Zimniak et al., 1994; Ji et al., 1997; Sundberg et al., 1998; Watson et al., 1998). Whereas GST and GST genes cluster on chromosomes 1 and 22, respectively, GSTP1 is encoded by a single locus on chromosome 11 (Ali-Osman et al., 1997), indicating a distinct genomic evolution among the GST family. GSTP1 was found up-regulated during development (Raijmakers et al., 2001) and associated with the integrity of the tumor suppressor gene p53 (Gudmundsdottir et al., 2001) and with k-ras mutations (Miyanishi et al., 2001).

---