Lead, calcium uptake, and related genetic variants in association with renal cell carcinoma risk in a cohort of male Finnish smokers.

Background: Lead is classified as a probable human carcinogen. However, its role in renal cell cancer (RCC) has not been established. Calcium and vitamin D may off-set toxicity in vivo . Methods: In this nested case–control study, whole blood lead, total serum calcium, and serum 25-hydroxyvitamin D levels were measured in blood drawn prior to diagnosis among male smokers participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Single-nucleotide polymorphisms (SNP) in five genes ( CALB1 , TRPV5 , TRPV6 , VDR , and ALAD ) related to lead toxicity or calcium transport were genotyped. Logistic and linear regressions were used to determine RCC risk and time to diagnosis (respectively), adjusting for other risk factors. Results: Among 154 newly diagnosed cases and 308 matched controls, RCC was associated with higher whole blood lead [OR = 2.0; 95% confidence interval (CI), 1.0–3.9; quartile 4 (Q4) vs. Q1, P trend = 0.022] and CALB1 rs1800645 ( P trend = 0.025, minor ‘T' allele frequency = 0.34). Higher total serum calcium ( P trend ≤ 0.001) was associated with reduced RCC risk. Total serum calcium and 25-hydroxyvitamin D levels did not alter the association observed with lead. Time from enrollment to RCC diagnosis was positively associated with serum calcium ( P trend = 0.002) and 25-hydroxyvitamin D ( P trend = 0.054) among cases. Conclusions: Higher blood lead concentrations, below the 10 μg/dL level of concern, were associated with RCC, independent from serum calcium and CALB1 promoter polymorphism. Impact: Increased risk of RCC is associated with lower serum calcium and higher whole blood lead in smokers. The clinical prognostic value of serum calcium and vitamin D in RCC should be further investigated. Cancer Epidemiol Biomarkers Prev; 21(1); 191–201. ©2011 AACR .