PAH–DNA adducts, GSTs, and breast cancer Table 3. Age-adjusted ORs (95% CIs) for the effects of number of variant genotypes, PAH–DNA adducts, and risk of breast cancer. PAH–DNA adduct status Cases (n) Controls (n) OR (95% CI) 1.00 1.01 (0.71 to 1.43) 0.56 (0.40 to 0.77) 0.97 (0.78 to 1.20) 0.78 (0.56 to 1.07) 0.82 (0.66 to 1.03) 0.93 (0.56 to 1.56) 1.56 (1.13 to 2.16) p-Valuea ICR (95% CI) Referent 0.60 (0.23 to 0.97) 0.36 (–0.12 to 0.84) 0.75 (0.20 to 1.30) Total 97 131 339 392 303 383 121 150 OR (95% CI) 1.0 0.98 (0.67 to 1.43) 0.96 (0.73 to 1.25) 0.91 (0.71 to 1.18) 0.89 (0.68 to 1.18) 0.88 (0.68 to 1.14) 1.44 (0.97 to 2.14) 1.18 (0.82 to 1.69) p-Valuea ICR (95% CI) Referent 0.30 (–0.13 to 0.72) 0.32 (–0.10 to 0.73) 0.15 (–0.47 to 0.77) 0.05 0.18 0.43 0.24 0.66 0.52 0.62 Common alleles: GSTT1 present, GSTM1 present, GSTP1 (AA), GSTA1 (A*/A*). Variant alleles: GSTT1 null, GSTM1 null, GSTP1 (AG or GG), GSTA1 (A*/B* or B*/B*). Symbols: +, PAH–DNA adducts detected; –, PAH–DNA adducts not detected. aFrom likelihood ratio test. Table 4. Age-adjusted ORs (95% CIs) for the effect of number of variant genotypes, smoking status, and risk of breast cancer. Smoking status Cases (n) Controls (n) Common alleles: GSTT1 present, GSTM1 present, GSTP1 (AA), GSTA1 (A*/A*). Variant alleles: GSTT1 null, GSTM1 null, GSTP1 (AG or GG), GSTA1 (A*/B* or B*/B*). aFrom likelihood ratio test. Table 5. Age-adjusted ORs (95% CIs) for the joint effect of GST polymorphisms and smoking on the out- come of detectable PAH–DNA adducts among control women. Smoking status Adducts not detected Adducts present OR (95% CI) p-Valuea ICR (95% CI) Multiple GSTs, PAHs, and breast can- cer risk. Table 3 illustrates the potential joint effects of PAH–DNA adducts and the num- ber of GST polymorphisms (one, two, or three or more variants) and breast cancer risk. We observed a 56% increase in risk (OR = 1.56; 95% CI, 1.13–2.16) among women with detectable adducts and three or more GST variants [GSTT1 variant, GSTM1 variant, GSTP1 AG/GG genotype, GSTA1 common (A*/B* or B*/B*) genotypes] com- pared with those with all common genotypes and no detectable PAH–DNA adducts. The corresponding OR for three or more variants and no detectable adducts was 0.93 (95% CI, 0.56–1.56). Women with one variant allele and no detectable adducts had a 44% reduced risk of breast cancer compared with women with all common alleles and no detectable adducts (OR, 0.56; 95% CI, 0.40–0.77); the corresponding OR for detectable adducts was not significant (OR, 0.97; 95% CI, 0.78–1.20; Table 3). As shown in Table 4, the ORs for the association between breast cancer risk and the number of GST variant alleles varied little with smoking status, and results for interaction on either a multiplicative or additive scale were not statistically significant. For example, the OR associated with three or more GST vari- ants was 1.18 among ever smokers (95% CI, 0.82–1.69) but was 1.44 among never smok- ers (95% CI, 0.97–2.14). Results for the inter- action between multiple GST variants and pack-years of smoking (data not shown) are similar to those shown in Table 4. When we categorized ever smokers by whether they were current or past smokers, the OR for the association between breast cancer risk and three or more GST vari- ants was 0.62 (95% CI, 0.27–1.43) among current smokers, and 1.66 (95% CI, 0.93– 2.97) among past smokers, compared with never smokers with all four common alleles. However, the category sizes upon which these estimates are based were small (data not shown), and the p-value for the interaction on a multiplicative scale was 0.31. GSTs, smoking, and PAH–DNA adducts among control women. We did not observe a significant association between any single GSTT1, GSTM1, GSTP1, or GSTA1 poly- morphism and detectable PAH–DNA adducts among the control women (GSTT1: OR, 1.09; 95% CI, 0.77–1.56; GSTM1: OR, 0.93; 95% CI, 0.69–1.25; GSTP1: OR, 0.95; 95% CI, 0.72–1.27; GSTA1: OR, 1.15; 95% CI, 0.86–1.53) or the number of variant geno- types and detectable PAH–DNA adducts (one variant compared with all common alleles: OR, 1.60; 95% CI, 0.92–2.79; two vari- ants compared with all common alleles: OR, 1.35; 95% CI, 0.77–2.36; three or more vari- ants compared with all common alleles: OR, 1.45; 95% CI, 0.75–2.82). Table 5 shows the 197 277 60 64 140 180 115 159 143 190 125 168 180 233 97 126 24 44 97 122 96 126 27 39 1.0 0.73 (0.53 to 0.99) 1.18 (0.74 to 1.87) 0.72 (0.43 to 1.20) 1.0 0.65 (0.45 to 0.93) 0.85 (0.57 to 1.26) 0.64 (0.43 to 0.93) 1.0 0.96 (0.69 to 1.34) 1.29 (0.88 to 1.91) 1.05 (0.72 to 1.52) 1.0 0.67 (0.47 to 0.96) 1.07 (0.71 to 1.62) 0.85 (0.57 to 1.26) 1.0 0.54 (0.26 to 1.15) 1.26 (0.78 to 2.03) 0.88 (0.55 to 1.42) 1.06 (0.65 to 1.75) 0.74 (0.45 to 1.21) 1.15 (0.56 to 2.35) 0.79 (0.39 to 1.58) 0.20 –0.37 (–1.04 to 0.31) 0.76 0.10 (–0.26 to 0.46) 0.18 –0.28 (–1.10 to 0.62) 0.41 –0.17 (–0.96 to 0.89) 0.13 Referent 0.28 (–0.39 to 0.45) –0.09 (–0.57 to 0.38) 0.18 (–0.23 to 0.59) No. of variants Four common One variant Two variants Three variants No. of variants Four common One variant Two variants Three or more variants Genotype GSTT1 Present Null Null GSTM1 Present GSTP1 AA (common) AG or GG GSTA1 A*/A* (common) A*/B* or B*/B* No. of variants Four common One variant Two variants Three variants – + – + – + – + Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever Never Ever 28 72 64 215 74 183 29 105 58 65 162 188 139 179 70 82 99 105 37 24 78 68 56 58 73 80 75 58 97 82 54 57 9 11 59 53 48 45 16 15 39 66 177 204 164 204 51 68 20 68 112 219 93 222 31 66 We adjusted data for age at reference and for season of blood draw. Common alleles: GSTT1 present, GSTM1 present, GSTP1 (AA), GSTA1 (A*/A*). Variant alleles: GSTT1 null, GSTM1 null, GSTP1 (AG or GG), GSTA1 (A*/B* or B*/B*). aFrom likelihood ratio test. Environmental Health Perspectives • volume 117 | number 4 | April 2009 555