RGD Reference Report - Copy number variations of GSTT1 and GSTM1, colorectal cancer risk and possible effect modification of cigarette smoking and menopausal hormone therapy. - Rat Genome Database

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Copy number variations of GSTT1 and GSTM1, colorectal cancer risk and possible effect modification of cigarette smoking and menopausal hormone therapy.

Authors: Rudolph, Anja  Hein, Rebecca  Hoffmeister, Michael  Försti, Asta  Hemminki, Kari  Risch, Angela  Brenner, Hermann  Chang-Claude, Jenny 
Citation: Rudolph A, etal., Int J Cancer. 2012 Sep 1;131(5):E841-8. doi: 10.1002/ijc.27428. Epub 2012 May 29.
RGD ID: 14700954
Pubmed: PMID:22234881   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.27428   (Journal Full-text)

Copy number variations (CNVs) of the glutathione-S-transferase θ-1 (GSTT1) and glutathione-S-transferase μ-1 (GSTM1) gene loci can lead to complete lack of enzyme and have been associated with colorectal cancer (CRC) risk. As GSTs are involved in the detoxification of xenobiotics, CNVs may modify CRC risk associated with smoking exposure and menopausal hormone therapy (MHT) use. We investigated CRC risk associated with GSTT1 and GSTM1 CNVs and their interaction with smoking in 1,796 cases and 1,806 age-, sex- and residence-matched controls from a German population-based case-control study (DACHS). The interaction with MHT was assessed in the subset of 684 postmenopausal female cases and 681 controls. Trimodular genotypes (0/0, 1/0 and 1/1) were determined with relative quantification based on multiplex real-time polymerase chain reaction. The associations with CRC risk as well as possible effect modifications were evaluated using conditional logistic regression analysis. CNVs of GSTT1 and GSTM1 were not significantly associated with CRC risk. Compared to the 1/1 genotype, odds ratios (ORs) for the 0/1 genotype and the 0/0 genotype were 0.89 [95% confidence interval (CI): 0.77-1.04] and 0.97 (95% CI: 0.80-1.18) for GSTT1, and 0.99 (95% CI: 0.78-1.27) and 1.03 (95% CI: 0.81-1.31) for GSTM1. Compared to the non-null genotype, ORs for the null-genotype were 1.04 (95% CI: 0.87-1.23) for GSTT1 and 1.03 (95% CI: 0.91-1.18) for GSTM1. No significant interaction with smoking and MHT use was observed. Our study does not provide evidence for a strong association between CRC risk and CNVs of GSTT1 or GSTM1 or for an effect modification of smoking or MHT use.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colorectal cancer no_associationIAGP 14700954; 14700954DNA:CNVsRGD 
colorectal cancer no_associationISOGSTM1 (Homo sapiens)14700954; 14700954DNA:CNVsRGD 
colorectal cancer no_associationISOGSTT1 (Homo sapiens)14700954; 14700954DNA:CNVsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gstm1  (glutathione S-transferase mu 1)
Gstt1  (glutathione S-transferase theta 1)

Genes (Mus musculus)
Gstm1  (glutathione S-transferase, mu 1)
Gstt1  (glutathione S-transferase, theta 1)

Genes (Homo sapiens)
GSTM1  (glutathione S-transferase mu 1)
GSTT1  (glutathione S-transferase theta 1)


Additional Information