Joint Effects of Dietary Trace Metals and DNA Repair Capacity in Lung Cancer Risk

Abstract

In a large case-control study, we previously reported that dietary intakes of zinc (Zn) and copper (Cu), but not selenium (Se), were inversely associated with lung cancer risk. Because Zn, Cu, Se, iron (Fe), and calcium (Ca) are important for maintaining DNA stability, we examined their associations with DNA repair capacity (DRC) measured by the lymphocyte host-cell reactivation assay in 1,139 cases and 1,210 of the controls. Dietary intake was reported in a food frequency questionnaire. In multivariate analyses, compared to those with high dietary Cu + proficient DRC, the odds ratio (95% confidence interval) [OR (95% CI)] for lung cancer for low Cu + suboptimal DRC was 2.54 (1.97-3.27). Similar results were observed for men and women. These effects were more pronounced in older and lean subjects, those with late-stage disease, and those with a family history of cancer in first-degree relatives. Compared to subjects with high Zn + proficient DRC, the OR for lung cancer for low Zn + suboptimal DRC was 1.82 (95% CI, 1.41-2.34), with pronounced effects in men, current smokers, subjects with longer duration of smoking, those with late-stage disease, or those with a family history of cancer. An OR of 1.94 (95% CI, 1.51-2.48) was observed for low Fe + suboptimal DRC compared with high Fe + proficient DRC, and pronounced effects appeared in older, lean subjects, those with longer duration of smoking, are heavier smokers, those with a late-stage disease, and those with a family history of cancer. No significant joint associations were seen for Se or Ca and DRC. Our joint associations between Cu-DRC, Zn-DRC and Fe-DRC and lung cancer risk require confirmation in prospective studies. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2756 -62)

Impact of inorganic nutrients on maintenance of genomic stability

“…It has been reported that selenium supplementation, in a form mainly composed of selenomethionine, reduces risk of prostate, colon, and lung cancer [Clark et al, 1996]. Another study documented an inverse relationship between risk of lung cancer and dietary intakes of zinc and copper, but not selenium [Mahabir et al, 2007].…”

Serum Copper and Zinc Levels Among Iranian Colorectal Cancer Patients

“…Trace elements are essential micronutrients that are involved in many important biological processes such as functioning as cofactors for the activity of the antioxidant enzymes, cell division, and differentiation [1,2]. Imbalances in levels of trace elements could adversely affect human health.…”

“…Exposure to reactive oxygen species (ROS) can lead to direct DNA damage, mutation, and carcinogenesis [6,7]. Previous studies have reported alterations in the concentrations of serum or neoplastic tissue trace elements in various carcinomas including breast, bladder, gastric, gallbladder, and lung cancers [1,[8][9][10][11][12].…”

Copper, Zinc, and Cu/Zn Ratio in Transitional Cell Carcinoma of the Bladder

“…They are cofactors for enzymes including Cu-Zn superoxide dismutase and DNA repair proteins, and also maintain DNA integrity [6,7]. Disturbed zinc and copper homeostasis has been associated with many types of cancer, such as gastrointestinal, lung, breast, and those of the female reproductive organs [8,9,10].…”