The choice of controls in a case-control study on WBC-DNA adducts and metabolic polymorphisms

The choice of the control group is a key issue in case-control studies, par ticularly in studies of molecular epidemiology. We discuss the potential bi as introduced by different options. To exemplify the consequences of differ ent choices, we have analysed two sets of controls in the context of a case -control study on bladder cancer: 55 were patients with urological conditio ns (cystitis, prostate hypertrophy), while 49 had a miscellany of medical o r surgical conditions. We measured DNA adducts in white blood cells (WBC) b y P-32-postlabelling and a series of metabolic polymorphisms (GSTM1, GSTT1, GSTP1, NAT2, NQO1). While no statistically significant differences were fo und for metabolic polymorphisms, the two series of controls showed differen t concentrations of DNA adducts, suggesting that conditions related to blad der cancer or intermediate steps leading to bladder cancer, such as chronic cystitis, may be associated with higher adduct levels. An association betw een DNA adduct levels and infection has been noted before in experimental a nimals: both in lung and in the skin, an inflammatory response increased th e biologically effective doses of polycyclic aromatic hydrocarbons. An alte rnative explanation is confounding; in fact, after adjustment for the level of consumption of fruit and vegetables (but not for smoking) the differenc e between the two control groups was no longer statistically significant. I n conclusion, the choice of controls in studies of molecular epidemiology h as subtle methodological implications, including confounding of metabolic/m olecular measurements by complex exposures such as diet.