For example, a profile that predisposes to hypercoagulability could be beneficial at very advanced ages but could predispose to cardiovascular diseases in middle-aged people. Accordingly, the lack of GSTT1 (or other phase 2 genes) could be related to deleterious effects at a young age (high risk of cancer) but could exert long-term beneficial effects on survival by avoiding the catabolism of important substances with chemopreventive effects on cancer and other diseases. Indeed, a recent study shows that among subjects consuming a diet rich in isothiocyanates (a lung carcinogen inhibitor), those with deletion of GSTM1 and/or GSTT1 have higher levels of this compound in the urine than subjects with the wild-type genotype. Another possibility is that the association between the GSTT1 locus and longevity regards a proximate locus of unknown nature whose variants are in linkage disequilibrium with the one studied. Further studies are needed to clarify this point.

Note: Nomenclature used: for CYP1A1, the term wild type refers to homozygotes for the common allele (absence of the restriction site), heterozygous refers to the presence of the polymorphism on one allele, homozygous refers to the presence of the restriction site on both alleles. For GSTM1 and GSTT1, null refers to homozygotes for deletion allele, while present refers to both homozygotes and heterozygotes (which cannot be distinguished by the experimental procedure).Luca, M., Giani, F., Cavallone, L., Cardelli, M., Giovagnetti, S., Amadio, L., Lisa, R., Tucci, M. G., Troiano, L., Pini, Guresi, P., Morellini, M., Sorbi, S., Passeri, G., Barbi, C., Sinisi, S., Monti, D., Deiana, L., Pes, G. M., Carru, C., and Schiavulli, L. (2005) Codon polymorphism and longevity: additional data on centenarians from continental Italy and Sardinia. Am. J. Hum. Genet., 76(2): 427-430.

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Roff D.A. and Bentzen P. (1989) The statistical analysis of mitochondrial DNA polymorphisms: chi-square and the problem of small samples. Mol. Biol. Evol. 6(5): 539-545.

Bladbjerg E.M., Andersen-Ranberg K., de Maat M.P.M., Kristensen S.R., Jeune B., Gram J. and Jespersen J. (1999) Longevity is independent of common variations in genes associated with cardiovascular risk. Thromb. Haemost. 82(4): 1100-1105.

Yashin A.I., De Benedictis G., Vaupel J.W., Tan Q., Andreev K.F., Iachine I.A., Bonafe M., De Luca M., Valensin S., Carotenuto L. and Franceschi C. (1999) Genes, demography, and life span: The contribution of demographic data in genetic studies on aging and longevity. Am. J. Hum. Genet. 65(4): 1178-1193.

De Benedictis G., Carotenuto L., Carrieri G., De Luca M., Falcone E., Rose G., Yashin A.I., Bonafe M. and Franceschi C. (1999) Age-related changes of the apolipoprotein B-VNTR allelic pool in ageing cohorts. Ann. Hum. Genet. 63(5): 369-377.

London S.J., Yuan J.M., Chung F.L., Gao Y.T., Coetzee G.A., Ross R.K. and Yu M.C. (2000) Diet-gene interaction in relation to lung cancer: a prospective study of isothiocyanates and glutathione S-transferase M1 and T1 genetic polymorphism among middle-aged men in Shanghai, China. Proc. Am. Cancer Res. 41: abstract no. 3316.