Potential role of gene-environment interactions in ion transport mechanisms in the etiology of renal cell cancer.
We investigated the ion transport mechanism (ITM) in renal cell cancer (RCC) etiology using gene-environment interactions between candidate single nucleotide polymorphisms (SNPs) and associated environmental factors, including dietary intakes of sodium, potassium and fluid, hypertension and diuretic medication. A literature-based selection of 13 SNPs in ten ITM genes were successfully genotyped in toenail DNA of 3,048 subcohort members and 419 RCC cases from the Netherlands Cohort Study. Diet and lifestyle were measured with baseline questionnaires. Cox regression analyses were conducted for main effects and gene-environment interactions. ADD1_rs4961 was significantly associated with RCC risk, showing a Hazard Ratio (HR) of 1.24 (95% confidence intervals (CI): 1.01-1.53) for the GT + TT (versus GG) genotype. Four of 65 tested gene-environment interactions were statistically significant. Three of these interactions clustered in SLC9A3_rs4957061, including the ones with fluid and potassium intake, and diuretic medication. For fluid intake, the RCC risk was significantly lower for high versus low intake in participants with the CC genotype (HR(95% CI): 0.47(0.26-0.86)), but not for the CT + TT genotype (P-interaction = 0.002). None of the main genetic effects and gene-environment interactions remained significant after adjustment for multiple testing. Data do not support the general hypothesis that the ITM is a disease mechanism in RCC etiology.
Departments of Epidemiology School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.
Ivette A G
IA
Deckers
Departments of Epidemiology School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.
Piet A
PA
van den Brandt
Departments of Pathology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.
Manon
M
van Engeland
Department of Toxicology, School for Nutrition, Toxicology and Metabolism (NUTRIM), MUMC, Maastricht, The Netherlands.
Frederik J
FJ
van Schooten
Department of Toxicology, School for Nutrition, Toxicology and Metabolism (NUTRIM), MUMC, Maastricht, The Netherlands.
Roger W L
RW
Godschalk
Department of Medical Informatics, Universitätsklinikum Aachen, Germany.
András P
AP
Keszei
Departments of Epidemiology School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.|Center for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
Janneke G F
JG
Hogervorst
Departments of Epidemiology School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands.
Leo J
LJ
Schouten
Nat Genet. 2011 Jan;43(1):60-5
21131975
J Hypertens. 1997 Jan;15(1):43-8
9050969
Cancer Epidemiol Biomarkers Prev. 2014 Jan;23(1):209-14
24220910
Eur J Hum Genet. 2009 Dec;17(12):1676-82
19491930
Nat Rev Genet. 2005 Apr;6(4):287-98
15803198
Int J Epidemiol. 1990 Sep;19(3):553-8
2262247
BMC Cancer. 2005 Jun 02;5:57
15932632
Lancet. 1997 May 10;349(9062):1353-7
9149697
Biometrics. 1994 Dec;50(4):1064-72
7786988
Transl Res. 2012 Aug;160(2):162-3
22677360
Hypertension. 1995 Mar;25(3):320-6
7875756
Carcinogenesis. 2010 Apr;31(4):614-20
20047954
Philos Trans R Soc Lond B Biol Sci. 2014 Feb 03;369(1638):20130092
24493741
Nat Rev Cancer. 2004 May;4(5):381-93
15122209
Clin Chem. 2007 Jun;53(6):1168-70
17517594
Circ Res. 1997 Jun;80(6):853-60
9168788
Cardiovasc Drugs Ther. 1993 Jan;7 Suppl 1:55-62
8435377
Hum Mol Genet. 2013 Feb 15;22(4):825-31
23184150
Am J Epidemiol. 1986 Jul;124(1):17-27
3521261
Cancer Causes Control. 2003 Jun;14 (5):427-38
12946037
Kidney Int. 1998 Jun;53(6):1471-8
9607177
Int J Cancer. 2015 Mar 1;136(5):1104-16
24978482
J Biol Chem. 1995 Aug 11;270(32):18990-6
7642559
Eur J Clin Nutr. 1995 Jun;49(6):420-9
7656885
Cell Mol Life Sci. 2000 Jun;57(6):884-95
10950304
Bioinformatics. 2005 Jan 15;21(2):263-5
15297300
Am J Physiol Regul Integr Comp Physiol. 2008 Jan;294(1):R66-75
17977920
PLoS One. 2015 Mar 31;10(3):e0122589
25826619
Hypertension. 1994 Apr;23(4):496-502
8144219
Br J Cancer. 2014 Feb 4;110(3):797-801
24327014
Cancer Epidemiol Biomarkers Prev. 2014 Dec;23(12):2703-12
25472680
Pharm Weekbl Sci. 1991 Apr 26;13(2):91-6
1870949
Nat Genet. 1998 Jul;19(3):282-5
9662405
J Hypertens. 2004 May;22(5):937-44
15097233
Hum Mol Genet. 2012 Jan 15;21(2):456-62
22010048
Nat Commun. 2013;4:2776
24220699
Nat Rev Urol. 2010 May;7(5):245-57
20448658
Eur J Clin Nutr. 1994 Apr;48(4):253-65
8039485
J Clin Oncol. 2000 Jun;18(11):2309-15
10829052
Urology. 2011 Apr;77(4):1005.e9-1005.e13
21477733
J Natl Cancer Inst. 2014 Mar;106(3):dju003
24563517
J Clin Epidemiol. 1990;43(3):285-95
2313318