B. Pesch et al. / Toxicology Letters 151 (2004) 283–290

Basic characteristics of the study population by age and gender

Reference population German Health Surveyd Octogenarians (N = 294) (N = 374) males; females (N = 205) males; females Age range (years) 17–79 70–79 80–98 Male gender 59% 43% 28% Ever smokers 59% 76%; 22% 41%; 13%e Mean BMIa (S.D.b) Not determined 27.8 (3.5); 27.9 (4.3) 23.6 (3.5); 22.3 (3.7) BMI >= 30kg/m2 Not determined 20%; 30% 2%; 4% Prevalence of diabetes mellitus Not determined 11%; 18% 17%; 13% Cancerc Subjects with cancer No data published 26%; 13% were not eligible Myocardial infarctiond Not determined 14%; 6% 21%; 17% Stroked Not determined Age-specific rates not published 17%; 18%

c Prevalence of survival after cancer, myocardial infarction or stroke; self-assessed. d German Health Survey 1998; subgroup aged 70–79 years from the West German population (Bellach, e Six missing data among females.

105IV genotypes and more homozygous 105VV genotypes than expected among non-cancer octoge- narians.

mean BMI (23 kg/m2) was lower than the mean BMI of the West German population aged 70–79 years (28 kg/m2; Bergmann and Mensink, 1999).

morphisms of the genes CYP1A1, CYP1B1, and GSTP1, and the frequencies of deletions in GSTM1 and GSTT1 in octogenarians and in the reference group. Among octogenarians, the CYP1B1 432L allele frequency was significantly decreased in comparison to the reference group (OR 0.63; 95% 0.40–1.00). In octogenarians, there were slightly less frequent GSTT1 deletions than in the non-cancer controls (OR 0.64; 95% CI 0.38–1.06). GSTM1 gene deletions were marginally more prevalent (OR 1.41; 95% CI 0.97–2.05).

4. Discussion

background of longevity is apparent (Gudmundsson et al., 2000; Heijmans et al., 2000; Perls et al., 2000). Besides rare genetic disorders, such as progeria with an early onset of senescence (Oshima, 2000), the ge- netic determinants of the human life span are still unknown. Genetic variants associated with an impact on reproduction, metabolism, radical scavenging, and signaling may affect the life span (Finch and Ruvkun, 2001). In Western populations, obesity, tobacco smok- ing, and male gender are associated with a variety of age-related diseases and, thus, with a lower life ex- pectancy. Smoking and high body fat content likely play a crucial role in ROS production. Among our study group of German octogenarians, ever smoking and obesity were less prevalent than in Germans aged 70–79 years recruited from the German Health Survey 1998 (Bellach, 1999; Bergmann and Mensink, 1999). This may be both an age-specific and a selection ef- fect of the enrollment from homes for the aged. Aging persons have a lower food intake, which contributes to the decline of BMI in the old, where severe forms

Table 3 shows the allelic variation in octogenarians by gender, but significant differences could not be re- vealed. In male octogenarians, there was a marginally significant lower prevalence of the CYP1B1 432LL P < . genotype than in women ( 0 10) (Table 3).

A further insight into the allelic differences re- sults from a stratification of the octogenarians by any diagnosis of cancer during lifetime with respect to the CYP1A1 461 N allele (OR 3.52; 95% CI 1.06–10.8), GSTP1 105V allele (OR 0.49; 95% CI 0.21–1.13), and GSTT1 deletion (OR 2.81; 95% CI 1.00–7.38) (Table 4). A significant deviation from the Hardy-Weinberg equilibrium could be demonstrated for GSTP1 I105V, with less observed heterozygous

Table 2

distributions, allele frequencies and deviations from Hardy-Weinberg equilibrium of CYP1A1 T461N, CYP1A1 3801 T > C, CYP1B1 V432L, GSTP1 I105V and in GSTM1 and GSTT1 in octogenarians and in a non-cancer reference group of age < 80 years

Sequence variation Reference group (17–79 years) Octogenarians (80–98 years) ORa (95% CI) Variant allele P-valueb (HWE) frequency RRc RVc VVc RR RV VV Ref Octo Ref Octo CYP1A1 T461N 269 (91.5%) 25 (8.5%) 0 176 (90.3%) 19 (9.7%) 0 1.16 0.59–2.27 0.04 0.05 1.00 1.00 CYP1A1 3801 T > C 238 (81.0%) 52 (17.7%) 4 (1.3%) 161 (80.5%) 39 (19.5%) 0 1.03 0.63–1.66 0.10 0.10 0.52 0.23 CYP1B1 V432L 51 (17.4%) 136 (46.3%) 107 (36.4%) 51 (25.0%) 105 (51.5%) 48 (23.5%) 0.63 0.40–1.00 0.60 0.49 0.54 0.78 GSTP1 I105V 128 (43.5%) 135 (45.9%) 31 (10.5%) 93 (46.0%) 68 (33.7%) 41 (20.3%) 0.90 0.62–1.32 0.34 0.37 0.69 0.00 Positive Negative Positive Negative Frequency of negatives GSTM1 153 141 88 114 1.41 0.97–2.05 0.48 0.56 GSTT1 233 61 174 29 0.64 0.38–1.06 0.21 0.14 a OR, odds ratio; and CI, confidence interval, for allele positivity of the variant allele.



a OR, odds ratio; and CI, confidence interval, for allele positivity of the variant b P-value (HWE), probability for deviation from Hardy-Weinberg equilibrium. c R, reference allele; V, variant allele according to the NCBI reference sequence.

Genotype distributions of CYPIAI T461N, CYPIAI 3801 T > C, CYPIBI V432L, GSTPI 1105V and deletions in GSTMI and GSTTI among octogenarians (aged 80-98years) by gender 

 Sequence Variation Octogenarians menOctogenarians women OR® (95% CI)Variant alleleP-value (HWE)?  frequencyRR RV vve RR RV VV Men Women Men WomenCYPIAI T461N 47 (85.4%) 8 (14.6%) 0 129 (92.1%) 11 (7.9%) 0 0.50 (0.17-1.53) 0.07 0.04 1.00 1.00CYPIAI 3801 T>C 43 (75.4%) 14 (24.6%) 0 118 (82.5%) 25 (17.5%) 0 0.65 (0.29-1.49) 0.12 0.09 0.58 0.60CYPIBI V432L 17 (29.3%) 33 (56.9%) 8 (13.8%) 34 (23.3%) 72 (49.3%) 40 (27.4%) 1.37 (0.64-2.83) 0.42 0.52 0.28 0.87GSTPI 1105V 29 (50.0%) 14 (24.1%) 15 (25.9%) 64 (44.4%) 54 (37.5%) 26 (18.1%) 1.25 (0.65-2.41) 0.38 0.37 <0.01 0.02Positive Negative Positive Negative Frequencyof negativesGSTMI1 30 27 58 87 1.67 (0.86-3.24) 0.47 0.60GSTT1 49 9 125 20 0.87 (0.35-2.33) 0.16 0.14 * OR, odds ratio; and CI, confidence interval, for allele le positivity of the variant allele.