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

Emily B. Southard, Alanna Roff, Tracey Fortugno, John P. Richie, Matthew Kaag, Vernon M. Chinchilli, Jarmo Virtamo, Demetrius Albanes, Stephanie Weinstein, Robin Taylor Wilson

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 Dlevels 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 mg/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.

Original languageEnglish (US)
Pages (from-to)191-201
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2012

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Renal Cell Carcinoma
Calcium
Serum
Vitamin D
Lead
beta Carotene
alpha-Tocopherol
Gene Frequency
Carcinogens
Single Nucleotide Polymorphism
Case-Control Studies
Linear Models
Logistic Models
Confidence Intervals
Genes

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

Cite this

Southard, Emily B. ; Roff, Alanna ; Fortugno, Tracey ; Richie, John P. ; Kaag, Matthew ; Chinchilli, Vernon M. ; Virtamo, Jarmo ; Albanes, Demetrius ; Weinstein, Stephanie ; Wilson, Robin Taylor. / Lead, calcium uptake, and related genetic variants in association with renal cell carcinoma risk in a cohort of male finnish smokers. In: Cancer Epidemiology Biomarkers and Prevention. 2012 ; Vol. 21, No. 1. pp. 191-201.
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abstract = "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 Dlevels 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 mg/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.",
author = "Southard, {Emily B.} and Alanna Roff and Tracey Fortugno and Richie, {John P.} and Matthew Kaag and Chinchilli, {Vernon M.} and Jarmo Virtamo and Demetrius Albanes and Stephanie Weinstein and Wilson, {Robin Taylor}",
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Lead, calcium uptake, and related genetic variants in association with renal cell carcinoma risk in a cohort of male finnish smokers. / Southard, Emily B.; Roff, Alanna; Fortugno, Tracey; Richie, John P.; Kaag, Matthew; Chinchilli, Vernon M.; Virtamo, Jarmo; Albanes, Demetrius; Weinstein, Stephanie; Wilson, Robin Taylor.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 21, No. 1, 01.01.2012, p. 191-201.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lead, calcium uptake, and related genetic variants in association with renal cell carcinoma risk in a cohort of male finnish smokers

AU - Southard, Emily B.

AU - Roff, Alanna

AU - Fortugno, Tracey

AU - Richie, John P.

AU - Kaag, Matthew

AU - Chinchilli, Vernon M.

AU - Virtamo, Jarmo

AU - Albanes, Demetrius

AU - Weinstein, Stephanie

AU - Wilson, Robin Taylor

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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 Dlevels 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 mg/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.

AB - 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 Dlevels 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 mg/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.

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