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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/22691

Title: Potential role of gene-environment interactions in ion transport mechanisms in the etiology of renal cell cancer
Authors: Deckers, Ivette A. G.
van den Brandt, Piet A.
van Engeland, Manon
van Schooten, Frederik J.
Godschalk, Roger W. L.
Keszei, Andras P.
Hogervorst, Janneke
Schouten, Leo J.
Issue Date: 2016
Citation: Scientific Reports, 6, p. 1-10 (Art N° 34262)
Abstract: 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.
Notes: [Deckers, Ivette A. G.; van den Brandt, Piet A.; Hogervorst, Janneke G. F.; Schouten, Leo J.] MUMC, Dept Epidemiol, Maastricht, Netherlands. [Deckers, Ivette A. G.; van den Brandt, Piet A.; Hogervorst, Janneke G. F.; Schouten, Leo J.] MUMC, Sch Oncol & Dev Biol GROW, Maastricht, Netherlands. [van Engeland, Manon] MUMC, Sch Oncol & Dev Biol GROW, Dept Pathol, Maastricht, Netherlands. [van Schooten, Frederik J.; Godschalk, Roger W. L.] MUMC, Sch Nutr Toxicol & Metab NUTRIM, Dept Toxicol, Maastricht, Netherlands. [Keszei, Andras P.] Univ Klinikum Aachen, Dept Med Informat, Aachen, Germany. [Hogervorst, Janneke G. F.] Hasselt Univ, Ctr Environm Sci, Diepenbeek, Belgium.
URI: http://hdl.handle.net/1942/22691
DOI: 10.1038/srep34262
ISI #: 000384344700001
ISSN: 2045-2322
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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