effect at such loci utilising this approach, the polymorphisms under study must have functional significance. In vitro studies have indicated that cells homozygous for the XRCC1 194W or 399Q have reduced DNA repair capacity (Wang et al. 2003; Takanami et al. 2005), and analysis of pro- tein function (based on amino acid sequence) predicts that the XRCC1 R399Q and XRCC3 T241M SNPs do have functional consequence for the protein product (Savas et al. 2004). The evidence from epidemiological studies is mixed, some studies indicate that some of the studied SNPs influence cancer risk (Goode et al. 2002; Ruttan and Glickman 2002; Zhu et al. 2003; Savas et al. 2004), e.g. for XRCC1 R194W a reduced risk of various types of cancer is associ- ated with the W allele (paradoxically, considering

Discussion

We have attempted to ascertain whether signifi- cant differences can be seen in the frequency of DNA repair enzyme gene polymorphisms in a population of neonates when compared to an aged population. In order to detect a selective

ageing individuals (Krichevsky et al. 2004) and multiply passaged lymphocyte clones (Neri et al. 2004). In the current study we have identified significantly different frequencies of certain inher- ited microsatellite sizes between newborns and aged individuals. However, these did not involve repeat sizes previously associated with pheno- typic effects (Price et al. 1997) and therefore we are not able to ascribe any functional significance to this at this time.

the in vitro evidence), whilst results for XRCC1 R399Q and XRCC3 T241M are inconsistent (Goode et al. 2002). The inconclusiveness of the genetic epidemiological evidence is likely due to the complex polygenic nature of any underlying genetic association. In addition, for the studied microsatellite loci, unusually large or small alleles are associated with clinical radiosensitiv- ity (Price et al. 1997) and hence may have sub- optimal DNA repair rates. It should be noted that no functional significance has yet been attributed to XRCC4 I134T. Although the poly- morphisms studied are in loci coding for pro- teins involved in repairing damage induced by metabolic by-products we find no evidence for dif- fering gene frequencies between neonates and our aged population. This suggests that in this case ei- ther the selective force is not strong enough to produce a detectable effect, or that these polymor- phisms are not of significance in this context. We note that many gene-longevity association studies examine centenarians as these are survivors lack- ing genetic variants associated with premature mortality (Lewis and Brunner 2004). Thus, it may be that our cases, although retired, were too young for a detectable effect. In support of this, it is of interest that, in an extension of an earlier study (King et al. 1994), the previously reported trend of an age-related increase in somatic HPRT mutations did not extend to a further group of 75–80 year-old individuals with this group having a lower frequency than a group aged 65–69 years (King et al. 1997). This would imply that it is only at this more advanced age that those having low frequencies of somatic mutations, and hence an efficient DNA damage recognition and repair sys- tem, are at a selective advantage. However, we are aware of the healthy worker effect whereby only healthy individuals pass the screening procedures associated with employment (Baillargeon 2001), and this is an important consideration when retired workers are studied. Such an effect could act as a surrogate selective process acting to mag- nify any age-related differences.

Acknowledgements

This work was funded by British Nuclear Fuels Limited. We would like to thank Mr Keith Binks (Epidemiology and Statistics Department, Westlakes Research Institute, for statistical advice).

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