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Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study

BACKGROUND: Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance o...

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Autores principales: Beebe-Dimmer, Jennifer L, Iyer, Priyanka T, Nriagu, Jerome O, Keele, Greg R, Mehta, Shilpin, Meliker, Jaymie R, Lange, Ethan M, Schwartz, Ann G, Zuhlke, Kimberly A, Schottenfeld, David, Cooney, Kathleen A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465173/
https://www.ncbi.nlm.nih.gov/pubmed/22747749
http://dx.doi.org/10.1186/1476-069X-11-43
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author Beebe-Dimmer, Jennifer L
Iyer, Priyanka T
Nriagu, Jerome O
Keele, Greg R
Mehta, Shilpin
Meliker, Jaymie R
Lange, Ethan M
Schwartz, Ann G
Zuhlke, Kimberly A
Schottenfeld, David
Cooney, Kathleen A
author_facet Beebe-Dimmer, Jennifer L
Iyer, Priyanka T
Nriagu, Jerome O
Keele, Greg R
Mehta, Shilpin
Meliker, Jaymie R
Lange, Ethan M
Schwartz, Ann G
Zuhlke, Kimberly A
Schottenfeld, David
Cooney, Kathleen A
author_sort Beebe-Dimmer, Jennifer L
collection PubMed
description BACKGROUND: Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. METHODS: Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case–control study in Southeastern Michigan and exposed to low to moderate (<50 μg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources. RESULTS: While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88). CONCLUSIONS: Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.
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spelling pubmed-34651732012-10-06 Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study Beebe-Dimmer, Jennifer L Iyer, Priyanka T Nriagu, Jerome O Keele, Greg R Mehta, Shilpin Meliker, Jaymie R Lange, Ethan M Schwartz, Ann G Zuhlke, Kimberly A Schottenfeld, David Cooney, Kathleen A Environ Health Research BACKGROUND: Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. METHODS: Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case–control study in Southeastern Michigan and exposed to low to moderate (<50 μg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources. RESULTS: While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88). CONCLUSIONS: Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings. BioMed Central 2012-06-29 /pmc/articles/PMC3465173/ /pubmed/22747749 http://dx.doi.org/10.1186/1476-069X-11-43 Text en Copyright ©2012 Beebe-Dimmer et al. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Beebe-Dimmer, Jennifer L
Iyer, Priyanka T
Nriagu, Jerome O
Keele, Greg R
Mehta, Shilpin
Meliker, Jaymie R
Lange, Ethan M
Schwartz, Ann G
Zuhlke, Kimberly A
Schottenfeld, David
Cooney, Kathleen A
Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study
title Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study
title_full Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study
title_fullStr Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study
title_full_unstemmed Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study
title_short Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study
title_sort genetic variation in glutathione s-transferase omega-1, arsenic methyltransferase and methylene-tetrahydrofolate reductase, arsenic exposure and bladder cancer: a case–control study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465173/
https://www.ncbi.nlm.nih.gov/pubmed/22747749
http://dx.doi.org/10.1186/1476-069X-11-43
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