Lead, calcium uptake, and related genetic variants in association with renal cell carcinoma risk in a cohort of male Finnish smokers.
Lead, calcium uptake, and related genetic variants in association with renal cell carcinoma risk in a cohort of male Finnish smokers.
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DOI：
10.1158/1055-9965.epi-11-0670
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Wilson RT
中科院分区：
文献类型：
--
作者：
Southard EB;Roff A;Fortugno T;Richie JP Jr;Kaag M;Chinchilli VM;Virtamo J;Albanes D;Weinstein S;Wilson RT
铅（Pb）被列为可能的人类致癌物。然而，其在肾细胞癌（RCC）中的作用尚未确定。钙和维生素D可抵消体内毒性。在这项巢式病例对照研究中，在诊断前对参加α-生育酚、β-胡萝卜素癌症预防研究的男性吸烟者进行全血铅（Pb）、血清总钙和血清25-羟基维生素D测定。对与铅毒性或钙转运相关的5个基因（CALB 1、TRPV 5、TRPV 6、VDR和ALAD）的单核苷酸多态性（SNP）进行基因分型。Logistic和线性回归分别用于确定RCC风险和诊断时间，并调整其他风险因素。在154例新诊断的肾细胞癌患者和308例对照组中，肾细胞癌患者的全血铅水平（OR=2.0，95% CI：1.0，3.9; Q4对Q1，P趋势=0.022）和CALB 1 rs 1800645水平（P趋势=0.025，T等位基因频率为0.34）高于正常人。较高的血清总钙（P趋势=<0.001）与肾细胞癌风险降低相关。总血清钙和25-羟维生素D水平并没有改变与铅观察到的关联。病例中从入组到诊断为RCC的时间与血清钙（P趋势=0.002）和25-羟基维生素D（P趋势=0.054）呈正相关。较高的血铅浓度，低于10微克/分升的关注水平，与肾细胞癌，独立于血清钙和CALB 1启动子多态性。吸烟者患肾细胞癌的风险增加与血清钙水平降低和全血铅水平升高有关。血清钙和维生素D在肾细胞癌中的临床预后价值有待进一步研究。
Lead (Pb) 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. In this nested case-control study, whole blood lead (Pb), total serum calcium, and serum 25-hydroxyvitamin D were measured in blood drawn prior to diagnosis among male smokers participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Single nucleotide polymorphisms (SNPs) in five genes (CALB1, TRPV5, TRPV6, VDR, and ALAD) related to lead toxicity or calcium transport were genotyped. Logistic and linear regression were used to determine RCC risk and time to diagnosis (respectively), adjusting for other risk factors. Among 154 newly diagnosed cases and 308 matched controls, RCC was associated with higher whole blood lead (OR=2.0, 95% CI:1.0,3.9; quartile 4 (Q4) v. Q1, Ptrend=0.022) and CALB1 rs1800645 (Ptrend=0.025, minor ‘T’ allele frequency=0.34). Higher total serum calcium (Ptrend=<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 (Ptrend=0.002) and 25-hydroxyvitamin D (Ptrend=0.054) among cases. Higher blood lead concentrations, below the 10 ug/dL level of concern, were associated with RCC, independent from serum calcium and CALB1 promoter polymorphism. 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.