Bulky DNA adducts as risk indicator of lung cancer in a Danish case‐cohort study

Abstract

Little is known of the predictive value of the levels of DNA adducts in terms of cancer risk. We examined the association between bulky DNA adducts and risk of lung cancer in a population-based cohort, comprising of 25,717 men and 27,972 women aged 50-64 years at entry. We included 245 cases (137 men and 108 women) with lung cancer and a comparison group of 255 individuals (137 men and 118 women), matched on sex, age and smoking duration. Bulky adducts in white blood cells collected at enrolment and stored at 2150°C were analyzed by 32 P-postlabeling method, using the butanol enrichment procedure. The median level of bulky DNA adducts was 0.196 adduct/10 8 nucleotides (5-95 percentiles: 0.094-0.595) among current smokers who were later diagnosed with lung cancer and 0.163 adduct/10 8 nucleotides (5-95 percentiles: 0.091-0.455) among current smokers in the comparison group. The smoking adjusted incidence rate ratios (IRR) for lung cancer in relation to one log unit (natural logarithm) difference in adduct levels were 1.22 (95% CI 0.85-1.74), 1.33 (95% CI 0.89-1.98) and 0.76 (95% CI 0.39-1.47) among all, current and former smokers, respectively. Current smokers with bulky DNA adduct levels above the median had a significant higher lung cancer rate than those with adduct levels below the median (IRR 5 1.61; 95% CI 1.04-2.49). The results are compatible with previous studies, suggesting a slightly higher risk of lung cancer with higher levels of adducts among smokers. Our results indicate that bulky DNA adducts may have a weak association with lung cancer risk. ' 2005 Wiley-Liss, Inc.

Bulky DNA adducts as risk indicators of lung cancer in a Danish case‐cohort study

“…As pointed out by Dr. Rundle, the effect of adjustment for smoking on the risk estimate for DNA adducts in our study 1 is too modest to justify meaningful interpretations. Nevertheless, the discussion about interpretation of an association after adjustment for an antecedent variable within a complex biological system is of general interest.…”

Letter to the editor, re “Bulky DNA adducts as risk indicators of lung cancer in a Danish case‐cohort study”

“…1 However, I was concerned by their interpretation of the results after adjustment for smoking behavior (duration, intensity and time since stopping). 1 Adjustment for smoking behavior produced the one statistically significant finding, changing the IRR for high adduct levels among smokers from 1.45 (0.96-2.19) to 1.61 (1.04-2.49) after control for smoking behavior, approximately a 28% change in beta.…”

“…1 However, I was concerned by their interpretation of the results after adjustment for smoking behavior (duration, intensity and time since stopping). 1 Adjustment for smoking behavior produced the one statistically significant finding, changing the IRR for high adduct levels among smokers from 1.45 (0.96-2.19) to 1.61 (1.04-2.49) after control for smoking behavior, approximately a 28% change in beta. In the Discussion the authors write ''The interpretation of the unadjusted results would be the effect of DNA adducts on lung cancer risk, whatever caused or modified the adduct levels, whereas the interpretation of the smoking-adjusted results would be the effect on lung cancer risk of adduct levels caused by anything but smoking''.…”

Genotoxicity: damage to DNA and its consequences

“…Detectable DNA adducts were significantly more common in non-smokers and longterm ex-smokers who developed lung cancer than in those who did not. The second study investigated 245 individuals with lung cancer and 255 without, from a population-based cohort of 53, 689 men and women [100]. The median level of DNA adducts was significantly higher for smokers who developed lung cancer than for those that did not.…”