A functional polymorphism in RGS6 modulates the risk of bladder cancer

David M Berman; Yunfei Wang; Zhengyu Liu; Qiong Dong; Lorri-Anne Burke; Lance A Liotta; Rory Fisher; Xifeng Wu

doi:10.1158/0008-5472.CAN-04-1916

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A functional polymorphism in RGS6 modulates the risk of bladder cancer

Journal article

Open access

Peer reviewed

A functional polymorphism in RGS6 modulates the risk of bladder cancer

David M Berman, Yunfei Wang, Zhengyu Liu, Qiong Dong, Lorri-Anne Burke, Lance A Liotta, Rory Fisher and Xifeng Wu

Cancer research (Chicago, Ill.), Vol.64(18), pp.6820-6826

09/15/2004

DOI: 10.1158/0008-5472.CAN-04-1916

PMID: 15375002

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Abstract

RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in bladder cancer risk. The risk of bladder cancer was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of bladder cancer (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of RGS6 are expressed in bladder cancer cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study.

RGS Proteins - genetics

Genetic Predisposition to Disease

Urinary Bladder Neoplasms - genetics

Humans

Middle Aged

RGS Proteins - biosynthesis

Female

Male

Polymorphism, Single Nucleotide

Urinary Bladder Neoplasms - metabolism

Case-Control Studies

Smoking

Details

Title: Subtitle: A functional polymorphism in RGS6 modulates the risk of bladder cancer
Creators: David M Berman - Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA. bermand@mail.nih.gov
Yunfei Wang
Zhengyu Liu
Qiong Dong
Lorri-Anne Burke
Lance A Liotta
Rory Fisher
Xifeng Wu
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.64(18), pp.6820-6826
DOI: 10.1158/0008-5472.CAN-04-1916
PMID: 15375002
NLM abbreviation: Cancer Res
ISSN: 0008-5472
eISSN: 1538-7445
Publisher: United States
Grant note: CA 91846 / NCI NIH HHS CA 74880 / NCI NIH HHS GM067881 / NIGMS NIH HHS
Language: English
Date published: 09/15/2004
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040213802771

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