Group Sex Male Female Age (years) ≤ 39 40–47 48–55 56–61 ≥ 62 Smokinga Never Former Current Total 21/48 8/23 0/0 2/5 1/13 9/20 17/33 13/28 9/23 7/20 29/71 69 31 0 7 14 29 50 41 32 27 100 interval (CI) of 1.07–1.60, and that the OR for the highest tertile was 1.4 (1.16–1.72). The assumption that the log OR is normally distributed leads to a normal distribution with mean value given by ln(1.3) = 0.26 and ln(1.4) = 0.33, respectively. The standard deviation of the normal distributions was found by solv- ing the equations 1n(1.3) + 1.96σ = 1n(1.60) and 1n(1.4) + 1.96 σ = 1n(1.72), which gave a standard deviation on the log odds scale of 0.1 in both cases. As suggested by Birkes and Dodge (1993) and Gelman et al. (1995), a simple way to provide a prior variance on the parameters β1 and β2 in the current study was to inflate the historical variance. To take into account the heterogeneity and other differ- ences between current and historical data, we considered the prior variance as a Gamma ran- dom variable which, on average, fluctuated around the inflating factor (60 in our case). Further prior information was obtained from International Agency for Research on Cancer (IARC) monograph on tobacco smoking (IARC 1986): (weighted) mean value of OR (current vs. never smokers) was considered 10 for lung cancer, 1.4 for oral cavity–digestive tract cancers, and 2.1 for genitourinary organ cancers. With regard to the Bayesian interval estimation of OR, we adopted the 95% cred- ibility interval (CrI) with the highest posterior density, that is, an interval of the OR posterior distribution such that the area under the curve is 0.95 and the density at any point inside the interval is greater than the density at any point outside. The traditional CI based on frequen- tist inference refers to repeated sampling, ran- dom intervals, and true parameter values (OR) and does not provide any estimates concerning the study that was actually conducted. On the contrary, CrI is a probability statement within the data set studied concerning the random variable OR and specifying the range within which the OR lies with 0.95 probability. To estimate if the GSTM1 and GSTT1 genotypes were a risk factor for all cancers, we used a similar multivariate anal- ysis, adding to the model M1 described in Equation 1 the variables GSTM1, GSTT1 (we called this model M2) and their interactions within CA (we called this model M3). The analysis performed to choose between compet- ing models was based on the BIC index, BIC = –21nLm + m1nn, where n is the sample size, m is the difference of the number of parameters in the models, and Lm is the likelihood ratio for the models. This criterion penalized mod- els that improved the fit, increasing the num- ber of parameters. The model with the lower value of BIC was the one to be preferred. Results The distribution of cases and controls in the whole database by country and by other vari- ables considered in the analysis is given in Environmental Health Perspectives • volume 117 | number 2 | February 2009 CA, cancer risk, and genetic polymorphism Table 1. The proportion of males and of cur- rent smokers was higher in the databases from Norway and Denmark. Smoking habit was not different between the cases and controls. The Italian subjects selected from the general population had a higher mean age, a higher proportion of women, and fewer current smokers than the Nordic groups. The distri- bution by tumor site of the 107 cancer cases included in the study is reported in Table 2. The distribution of GST polymorphisms did not differ significantly in the three coun- tries, and therefore all data were combined before analysis (Table 3). No significant dif- ferences were evident in the genotype distribu- tion of cases and controls, with genotype prevalence of 52.4 and 50.5% for GSTM1 and 29.9 and 29.8% for GSTT1, respectively. Accordingly, the mean frequency of CA did not appear to be modulated by genotype (Table 3). Table 1. Number of cancer cases and controls classified according to sex, age, and smoking status. Italy Case/control Total Norway Case/control Denmark Case/control Total Total Case/control Genotype Cases (%) Total Controls (%) Total (%) Mean CA % Cases (SE) Controls (SE) Total (SE) GSTM1 Null Positive All GSTT1 Null Positive All 55 (52.4) 50 (47.6) 105 23 (29.9) 54 (70.1) 77 141 (50.5) 138 (49.5) 279 65 (29.8) 153 (70.2) 218 196 (51) 188 (49) 384 88 (29.8) 207 (70.2) 295 2.13 (0.2) 1.83 (0.2) 1.42 (0.1) 1.47 (0.1) 1.78 (0.36) 1.80 (0.17) 1.20 (0.15) 1.46 (0.12) 1.62 (0.1) 1.57 (0.1) 1.35 (0.2) 1.55 (0.1) aBecause of the limited amount of DNA retrieved from stored specimen, only 105/107 cases were genotyped for GSTM1 and 77/107 for GSTT1. 64/165 2/6 13/44 12/41 20/39 7/34 14/13 25/61 7/21 33/81 66 /171 Italy 0 1 1 4 3 4 0 6 0 2 1 0 1 2 1 3 29 Total 229 8 57 53 59 41 27 86 28 114 237 1 0 3 8 2 1 1 5 19 0 0 1 6 4 2 13 66 12/49 0/0 5/16 1/19 4/10 2/4 0/0 4/22 5/19 3/8 12/49 aAt the time of CA sampling. For one case and eight controls from Norway, no data were available on smoking status. Table 2. Distribution of cancer cases included in the nested case–control study by site and country. No. of cases Norway Denmark Tumor site (ICD–9 code)a Oral cavity (140–149) Esophagus (150) Stomach (151) Intestine, colon, and rectum (152–154) Liver (155) Pancreas (157) Larynx (161) Lung (162) Bone, skin (170–173) Breast (174) Uterus (179,182) Ovary (183) Prostate (185) Bladder (188) Kidney (189) Other sites Total aInternational Classification of Diseases, 9th Revision (WHO 1975). Table 3. Distribution of GSTM1 and GSTT1 genotypes in cases and controls and mean CA frequency.a 97/262 10/29 18/60 15/65 25/62 18/58 31/46 42/111 21/63 43/109 107/291 Total 2 1 4 13 5 5 1 12 20 2 1 1 7 7 3 23 107 Total (%) 359 (90.2) 39 (9.8) 78 (19.6) 80 (20.1) 87 (21.9) 76 (19.1) 77 (19.3) 153 (38.4) 84 (21.1) 152 (38.2) 398 (100) Percent of all cases 1.9 0.9 3.7 12.1 4.7 4.7 0.9 11.2 18.7 1.9 0.9 0.9 6.5 6.5 2.8 21.5 100.0 1 0 0 1 0 0 0 1 1 0 0 0 0 1 0 7 12 61 0 21 20 14 6 0 26 24 11 61 Two-sample Kolmogorov–Smirnov test of identical distribution functions (null vs. positive) p = 0.69 p = 0.67 205