Table 1. Characteristics of the study population: SAPALDIA cohort. manner. A 10 µg/m3 decline in PM10 over an 11-year period was associated with an average attenuation of annual decline in FEF25–75 of 6.0 mL/year [95% confidence interval (CI), –4.54 to 16.54] in participants with an AA genotype, 13.7 mL/year (5.38–22.06) in heterozygous AG participants, and 21.3 mL/year (10.57– 32.08) in participants with a GG genotype. For the CCND1 rs667515 SNP, the bene- ficial ΔPM10 effect was most pronounced in participants homozygous for the minor allele (CC genotype) and attenuated annual FEF25–75 decline in this subgroup by 28.83 mL/ year (95% CI, 15.60–42.07) compared with 10.39 (3.24–20.47) and 11.83 (1.32–19.47) among GG and GC genotypes, respectively. This effect modification thus followed a reces- sive genetic model. Characteristic Female (%) Swiss nationality (%) Educational level in 2002 (professional education or higher, %) Increase in educational level between surveys (%) Age in 1991 [mean ± SD (years)] Height [mean ± SD (cm)] BMI in 1991 [mean ± SD (kg/m2)] BMI change [mean ± SD (kg/m2)] Smoking Never-smokers in 1991 (%) Never-smokers in 2002 (%) Smoking quitters during follow-up (%) Current smokers in 1991 (%) Current smokers in 2002 (%) No. of pack-years for current smokers in 2002 [median (IQR)] Cigarettes per day for current smokers in 1991 [median (IQR)] Cigarettes per day for current smokers in 2002 [median (IQR)] Passive smoking and occupational exposure (%) ETS exposure in never-smokers in 1991 ETS exposure in never-smokers in 2002 Father or mother smoked during childhood Workplace exposure to dust and fumes in 1991 Workplace exposure to dust and fumes in 2002 Atopy in 1991 Change in average individual home outdoor PM10 exposurea All areas (n = 4,326) Basel area (n = 486) Wald area (n = 889) Davos area (n = 318) Lugano area (n = 568) Montana area (n = 431) Payerne area (n = 595) Aarau area (n = 689) Geneva area (n = 350) Lung function in 1991 [mean ± SD (L)]b FVC in women FVC in men FEV1 in women FEV1 in men FEF25–75 in women FEF25–75 in men IQR, interquartile range. aPM10 (µg/m3) in the year before SAPALDIA1 minus PM10 in the year before SAPALDIA2. bWomen, n = 2,293; men, n = 2,033. cGenotype distribution: p21 CA, n = 594; p21 AA, n = 31. dDiplo- type distribution is labeled as follows: –/–, none of the specific haplotype present; (rs667515, rs9344)/– (e.g., GG/–), one of the specific haplotypes present; (rs667515, rs9344)/(rs667515, rs9344) (e.g., GG/GG), for two of the specific haplotypes present. Environmental Health Perspectives • volume 117 | number 9 | September 2009 1423 For the p53 R72P SNP, the observed effect modification followed a codominant model. ΔPM10 was associated with an aver- age attenuation of annual FEF25–75 decline by an average of 17.4 mL/year (95% CI, 8.95– 25.78) in GG genotypes (Pro/Pro) and by an average of 11.6 mL/year (2.65–20.61) in CG genotypes (Arg/Pro) but no attenuation in CC genotypes (Arg/Arg). CCND1 haplotypes 2 and 3, but not 1 and 4, were also statistically significant modifiers of the ΔPM10 association with FEF25–75 decline. In participants exhibiting the CCND1 haplotype 3 (CG/CG) on both alleles (representing the combination of the single SNP alleles associated with the greatest lung function attenuation), the effect estimate for attenuation of FEF25–75 decline associated Participants (n = 4,326) Characteristic p53, CCND1, and p21 variants modify PM10 effect with ΔPM10 was 30.9 mL/year (95% CI, 17.21–44.58) compared with 11.92 (3.40– 20.44) and 10.28 (1.22–19.35) among sub- jects with the CG haplotype in one or none of their alleles (Table 2). Genotype-specific ΔPM10 effect estimates for the attenuation of the average annual decline in FEV1 and FVC are presented in Supplemental Material, Table 5 (doi:10.1289/ ehp.0800430.S1). For FEV1 decline, effect modification by genotypes was comparable to that seen for FEF25–75 decline. Again, effect modification was strongest for the CCND1 rs667515 SNP and for CCND1 haplo- type3 [see Supplemental Material, Table 5 (doi:10.1289/ehp.0800430.S1)] We observed no modification of the ΔPM10 effect on FVC decline for any of the SNPs or haplotypes. 53.0 87.7 27.9 17.9 41.3 ± 11.2 169.3 ± 8.8 23.7 ± 3.6 2.1 ± 2.2 48.4 49.3 8.1 29.3 21.9 26.7 (14.0–42.6) 20 (10–25) 15 (7–20) 13.1 7.7 56.1 30.3 13.2 22.3 –5.8 (–7.3 to –4.2) –8.0 (–9.1 to –6.9) –4.5 (–4.8 to –3.9) –3.0 (–3.1 to –2.8) –12.1 (–13.5 to –10.8) –4.0 (–4.2 to –3.7) –5.0 (–5.3 to –4.6) –6.4 (–6.8 to –5.8) –6.2 (–7.3 to –5.7) 3.82 ± 0.61 5.30 ± 0.82 3.07 ± 0.55 4.11 ± 0.72 3.07 ± 1.00 3.79 ± 1.29 Annual change [mean ± SD) (mL/year)]b FVC in women FVC in men FEV1 in women FEV1 in men FEF25–75 in women FEF25–75 in men Genotype distribution p53 P72R, rs1042522 GG CG CC p21 S31R, rs1801270 CC CA or AAc CCND1 P242P, rs9344 GG GA AA CCND1 –7006G>C, rs667515 GG GC CC Diplotype distributiond CCND1 haplotype 1 (rs667515, rs9344) –/– GG/– GG/GG CCND1 haplotype 2 (rs667515, rs9344) –/– GA/– GA/GA CCND1 haplotype 3 (rs667515, rs9344) –/– CG/– CG/CG CCND1 haplotype 4 (rs667515, rs9344) –/– CA/– CA/CA Participants (n = 4,326) –20.79 ± 34.11 –29.17 ± 45.47 –31.88 ± 25.72 –39.77 ± 32.91 –68.89 ± 58.88 –74.11 ± 70.24 2,407 1,637 282 3,701 625 1,211 2,140 975 1,628 2,058 640 3,125 1,088 113 1,251 2,150 925 1,678 2,048 600 4,239 84 3