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Occupational bladder cancer: Polymorphisms of xenobiotic metabolizing enzymes, exposures, and prognosis.

Abstract Approximately 7% of all bladder cancer cases in males are associated with occupation. The question arises whether the use of genome-wide association studies was able to identify bladder cancer risk factors that may modulate occupational bladder cancer risk and prognosis. One hundred and forty-three bladder cancer cases with suspected occupational bladder cancer and 337 controls were genotyped for the following polymorphisms: N-acetyltransferase 2 (NAT2), glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), UDP-glucuronyltransferase 1A rs11892031 (UGT1A), rs9642880 (close to c-MYC), and rs710521 (close to TP63). The most relevant polymorphisms for occupational bladder cancer risk were GSTM1 and UGT1A, especially when co-occurring (GSTM1 negative and rs11892031[A/A]: 48% cases vs. 38% controls, OR 1.47, 95% CI 0.99-2.20). The effect was more pronounced in smokers. GSTM1 negative genotype occurred more frequently in cancer cases exposed to aromatic amines, carbolineum, and in painters and varnishers. UGT1A (rs11892031[A/A]) was found frequently in cases exposed to carbolineum, crack test spray, PAH, and in painters and varnishers. All investigated polymorphisms except rs710521 (TP63) seemed to exert an impact on recurrence risk. Relapse-free times were shorter for NAT2 slow and ultra-slow, GSTT1 positive and GSTM1 negative cases. Occupational bladder cancer cases with a number of risk variants displayed significantly shorter relapse-free times compared to cases with few, less relevant risk alleles as evidenced by median difference 8 months. In conclusion, in the present, suspected occupational bladder cancer cases phase II polymorphisms involved in bladder carcinogen metabolism modulate bladder cancer recurrence. Most relevant for bladder cancer risk were GSTM1 and UGT1A but not NAT2.
PMID
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Authors

Mayor MeshTerms

Polymorphism, Genetic

Keywords
Journal Title journal of toxicology and environmental health. part a
Publication Year Start




PMID- 28696839
OWN - NLM
STAT- MEDLINE
DA  - 20170711
DCOM- 20170830
LR  - 20170830
IS  - 1528-7394 (Print)
IS  - 0098-4108 (Linking)
VI  - 80
IP  - 7-8
DP  - 2017
TI  - Occupational bladder cancer: Polymorphisms of xenobiotic metabolizing enzymes,
      exposures, and prognosis.
PG  - 439-452
LID - 10.1080/10937404.2017.1304731 [doi]
AB  - Approximately 7% of all bladder cancer cases in males are associated with
      occupation. The question arises whether the use of genome-wide association
      studies was able to identify bladder cancer risk factors that may modulate
      occupational bladder cancer risk and prognosis. One hundred and forty-three
      bladder cancer cases with suspected occupational bladder cancer and 337 controls 
      were genotyped for the following polymorphisms: N-acetyltransferase 2 (NAT2),
      glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1),
      UDP-glucuronyltransferase 1A rs11892031 (UGT1A), rs9642880 (close to c-MYC), and 
      rs710521 (close to TP63). The most relevant polymorphisms for occupational
      bladder cancer risk were GSTM1 and UGT1A, especially when co-occurring (GSTM1
      negative and rs11892031[A/A]: 48% cases vs. 38% controls, OR 1.47, 95% CI
      0.99-2.20). The effect was more pronounced in smokers. GSTM1 negative genotype
      occurred more frequently in cancer cases exposed to aromatic amines, carbolineum,
      and in painters and varnishers. UGT1A (rs11892031[A/A]) was found frequently in
      cases exposed to carbolineum, crack test spray, PAH, and in painters and
      varnishers. All investigated polymorphisms except rs710521 (TP63) seemed to exert
      an impact on recurrence risk. Relapse-free times were shorter for NAT2 slow and
      ultra-slow, GSTT1 positive and GSTM1 negative cases. Occupational bladder cancer 
      cases with a number of risk variants displayed significantly shorter relapse-free
      times compared to cases with few, less relevant risk alleles as evidenced by
      median difference 8 months. In conclusion, in the present, suspected occupational
      bladder cancer cases phase II polymorphisms involved in bladder carcinogen
      metabolism modulate bladder cancer recurrence. Most relevant for bladder cancer
      risk were GSTM1 and UGT1A but not NAT2.
FAU - Lukas, Cordula
AU  - Lukas C
AD  - a Institute for Occupational, Social and Environmental Medicine , Castrop-Rauxel 
      , Germany.
FAU - Selinski, Silvia
AU  - Selinski S
AD  - b Leibniz Research Centre for Working Environment and Human Factors at TU
      Dortmund (IfADo) , Dortmund , Germany.
FAU - Prager, Hans-Martin
AU  - Prager HM
AD  - a Institute for Occupational, Social and Environmental Medicine , Castrop-Rauxel 
      , Germany.
FAU - Blaszkewicz, Meinolf
AU  - Blaszkewicz M
AD  - b Leibniz Research Centre for Working Environment and Human Factors at TU
      Dortmund (IfADo) , Dortmund , Germany.
FAU - Hengstler, Jan G
AU  - Hengstler JG
AD  - b Leibniz Research Centre for Working Environment and Human Factors at TU
      Dortmund (IfADo) , Dortmund , Germany.
FAU - Golka, Klaus
AU  - Golka K
AD  - b Leibniz Research Centre for Working Environment and Human Factors at TU
      Dortmund (IfADo) , Dortmund , Germany.
LA  - eng
PT  - Journal Article
DEP - 20170711
PL  - England
TA  - J Toxicol Environ Health A
JT  - Journal of toxicology and environmental health. Part A
JID - 100960995
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Genome-Wide Association Study
MH  - Germany
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Occupational Diseases/diagnosis/*genetics
MH  - *Polymorphism, Genetic
MH  - Prognosis
MH  - Risk Factors
MH  - Urinary Bladder Neoplasms/diagnosis/*genetics
EDAT- 2017/07/12 06:00
MHDA- 2017/08/31 06:00
CRDT- 2017/07/12 06:00
AID - 10.1080/10937404.2017.1304731 [doi]
PST - ppublish
SO  - J Toxicol Environ Health A. 2017;80(7-8):439-452. doi:
      10.1080/10937404.2017.1304731. Epub 2017 Jul 11.