title: Lead, calcium uptake, and related genetic variants in association with renal cell carcinoma risk in a cohort of male Finnish smokers.
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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Public Health Sciences, Penn State College of Medicine, Penn State Cancer Institute, 500 University Drive, Mail Code CH69, Hershey, PA 17033, USA.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Southard
authors.forename: Alanna
authors.initials: A
authors.lastname: Roff
authors.forename: Tracey
authors.initials: T
authors.lastname: Fortugno
authors.forename: John P
authors.initials: JP
authors.lastname: Richie
authors.forename: Matthew
authors.initials: M
authors.lastname: Kaag
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Stephanie
authors.initials: S
authors.lastname: Weinstein
authors.forename: Robin Taylor
authors.initials: RT
authors.lastname: Wilson
mesh_terms: D000368:Aged; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000097:blood* / Q000493:pharmacokinetics; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005387:Finland; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D007854:Lead / Q000097:blood* / Q000493:pharmacokinetics; D007855:Lead Poisoning / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D012907:Smoking / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000097:blood
chemical_list: C576498:CALB1 protein, human; D064092:Calbindin 1; D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D014807:Vitamin D; D007854:Lead; D002118:Calcium
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D108-10
references.pmid: 16381825
references.citation: Annu Rev Public Health. 1997;18:187-210
references.pmid: 9143717
references.citation: Urology. 2008 Feb;71(2):278-82
references.pmid: 18308103
references.citation: Am J Physiol Renal Physiol. 2009 May;296(5):F1042-51
references.pmid: 19261737
references.citation: Cancer. 2007 Aug 1;110(3):543-50
references.pmid: 17577222
references.citation: Am J Epidemiol. 1988 Sep;128(3):655-66
references.pmid: 2458036
references.citation: Epidemiology. 1997 Jan;8(1):31-6
references.pmid: 9116091
references.citation: IARC Monogr Eval Carcinog Risks Hum. 2006;87:1-471
references.pmid: 17191367
references.citation: Environ Res. 2006 Sep;102(1):61-9
references.pmid: 16487505
references.citation: Nat Struct Mol Biol. 2006 Jul;13(7):641-7
references.pmid: 16799559
references.citation: Environ Int. 2011 Jan;37(1):248-57
references.pmid: 20825992
references.citation: Eur J Clin Invest. 2005 May;35(5):290-304
references.pmid: 15860041
references.citation: Ann Oncol. 2011 Feb;22(2):295-300
references.pmid: 20657034
references.citation: N Engl J Med. 2006 Feb 16;354(7):684-96
references.pmid: 16481636
references.citation: Biochim Biophys Acta. 1994 May 25;1226(2):131-7
references.pmid: 8204659
references.citation: Cancer Causes Control. 2003 Oct;14(8):705-14
references.pmid: 14674734
references.citation: Toxicology. 1999 May 3;134(1):19-26
references.pmid: 10413185
references.citation: PLoS One. 2008 Feb 27;3(2):e1686
references.pmid: 18301763
references.citation: Environ Res. 1997 Jan;72(1):45-55
references.pmid: 9012371
references.citation: Curr Opin Nephrol Hypertens. 2000 Jul;9(4):341-7
references.pmid: 10926169
references.citation: Biochemistry. 2009 Sep 15;48(36):8603-14
references.pmid: 19658395
references.citation: Environ Sci Technol. 2009 Mar 1;43(5):1618-23
references.pmid: 19350944
references.citation: Eur J Endocrinol. 2010 May;162(5):979-86
references.pmid: 20156969
references.citation: Am J Epidemiol. 2001 Jul 1;154(1):1-13
references.pmid: 11427399
references.citation: Basic Clin Pharmacol Toxicol. 2007 Aug;101(2):96-100
references.pmid: 17651309
references.citation: Acta Oncol. 2002;41(4):381-8
references.pmid: 12234031
references.citation: Environ Health Perspect. 2002 Apr;110(4):325-9
references.pmid: 11940448
references.citation: Environ Health Perspect. 2006 Oct;114(10):1538-41
references.pmid: 17035139
references.citation: Environ Health Perspect. 2003 Oct;111(13):1613-9
references.pmid: 14527840
references.citation: Ann N Y Acad Sci. 2006 Sep;1076:29-53
references.pmid: 17119192
references.citation: Cancer Invest. 2005;23(3):240-55
references.pmid: 15945510
references.citation: J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):401-4
references.pmid: 15225809
references.citation: Eur J Cancer Prev. 2002 Apr;11(2):171-8
references.pmid: 11984136
references.citation: Am J Epidemiol. 2010 Jul 1;172(1):47-57
references.pmid: 20562187
references.citation: Eur J Cancer. 1996 Apr;32A(4):673-82
references.pmid: 8695272
references.citation: Cancer. 2008 Sep 1;113(5 Suppl):1213-24
references.pmid: 18720377
references.citation: Curr Oncol Rep. 2010 May;12(3):193-201
references.pmid: 20425079
references.citation: Am J Epidemiol. 2007 Oct 15;166(8):932-40
references.pmid: 17656615
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2984-8
references.pmid: 8464915
references.citation: Toxicology. 2002 Jul 1;176(1-2):1-9
references.pmid: 12062925
references.citation: J Bone Miner Res. 2008 Sep;23(9):1417-25
references.pmid: 18410230
references.citation: Annu Rev Physiol. 2002;64:529-49
references.pmid: 11826278
references.citation: Am J Ind Med. 2000 Sep;38(3):244-54
references.pmid: 10940962
references.citation: Am J Ind Med. 2000 Sep;38(3):316-23
references.pmid: 10940970
references.citation: J Nutr. 1991 May;121(5):718-28
references.pmid: 2019881
references.citation: Am J Epidemiol. 2009 Jul 1;170(1):88-94
references.pmid: 19406919
references.citation: Evid Rep Technol Assess (Full Rep). 2009 Aug;(183):1-420
references.pmid: 20629479
references.citation: J Natl Cancer Inst. 2008 Nov 19;100(22):1581-91
references.pmid: 19001601
references.citation: Pflugers Arch. 2009 May;458(1):99-109
references.pmid: 18989697
references.citation: Occup Environ Med. 1995 Feb;52(2):73-81
references.pmid: 7757170
references.citation: J Nutr. 1981 Apr;111(4):694-8
references.pmid: 6260915
references.citation: Scand J Work Environ Health. 1975 Dec;1(4):219-32
references.pmid: 1228901
references.citation: Clin Nutr. 2007 Aug;26(4):400-8
references.pmid: 17499891
references.citation: Ann Epidemiol. 1994 Jan;4(1):1-10
references.pmid: 8205268
references.citation: Environ Health Perspect. 2007 Jul;115(7):1018-22
references.pmid: 17637916
references.citation: J Natl Cancer Inst. 2002 Mar 20;94(6):437-46
references.pmid: 11904316
references.citation: J Nephrol. 2010 Nov-Dec;23 Suppl 16:S112-7
references.pmid: 21170867
references.citation: Environ Health Perspect. 2000 Oct;108(10):949-54
references.pmid: 11049814
references.citation: Environ Health Perspect. 2005 Dec;113(12):1669-74
references.pmid: 16330345
references.citation: Stat Med. 1997 May 15;16(9):965-80
references.pmid: 9160492
references.citation: Nat Methods. 2008 Sep;5(9):829-34
references.pmid: 19160518
references.citation: Arch Intern Med. 2002 Nov 25;162(21):2443-9
references.pmid: 12437403
references.citation: J Trace Elem Med Biol. 2006;20(3):171-9
references.pmid: 16959594
references.citation: Mutat Res. 2003 Dec 10;533(1-2):121-33
references.pmid: 14643416
references.citation: Hum Mol Genet. 2008 Jun 1;17(11):1613-8
references.pmid: 18276610
references.citation: Mol Endocrinol. 2000 Mar;14(3):401-20
references.pmid: 10707958