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Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women.

ABSTRACT: Enzymes encoded by the glutathione S-tranferase mu 1 (GSTM1) and pi 1 (GSTP1) genes, which are expressed in breast tissue, catalyze the detoxification of endogenous and exogenous electrophiles. Reduced enzyme activity, due to carriage of the GSTM1 deletion or the GSTP1 Ile105Val Val allele, may therefore affect susceptibility to breast cancer and related conditions. In a case-control study of Chinese women, we examined whether these polymorphisms were associated with risk of breast cancer and fibrocystic breast conditions. Women diagnosed with breast cancer (n=615) or fibrocystic breast conditions (n=467) were compared to women without clinical breast disease (n=878). We also examined whether these associations differed by menopausal status or by presence of proliferation in the extra-tumoral epithelium among women with breast cancer and in lesions among women with fibrocystic conditions. No overall association of either GST polymorphism with risk of breast cancer or fibrocystic breast conditions was observed. There was some evidence of slightly elevated cancer risk associated with carriage of the GSTM1 null genotype and at least one GSTP1 105-Val allele (OR=1.33, 95% CI, 0.99-1.80), compared to carriage of the GSTM1 non-null and GSTP1 Ile/Ile genotypes. This relationship was stronger in women who had breast cancer with extra-tumoral tissue proliferation (OR=1.77, 95% CI, 1.03-3.04). Our results suggest that GSTM1 and GSTP1 genotypes do not individually influence susceptibility to breast cancer or fibrocystic breast conditions. The observed increased risk of breast cancer associated with joint carriage of the GSTM1 null genotype and GSTP1 105-Val allele needs confirmation in other studies.

SUBMITTER: Sakoda LC

PROVIDER: S-EPMC2741390 | biostudies-other | 2008 May

REPOSITORIES: biostudies-other

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Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women.

Sakoda Lori C LC Blackston Christie R CR Xue Kan K Doherty Jennifer A JA Ray Roberta M RM Lin Ming Gang MG Stalsberg Helge H Gao Dao Li DL Feng Ziding Z Thomas David B DB Chen Chu C

Breast cancer research and treatment 20070712 1

Enzymes encoded by the glutathione S-tranferase mu 1 (GSTM1) and pi 1 (GSTP1) genes, which are expressed in breast tissue, catalyze the detoxification of endogenous and exogenous electrophiles. Reduced enzyme activity, due to carriage of the GSTM1 deletion or the GSTP1 Ile105Val Val allele, may therefore affect susceptibility to breast cancer and related conditions. In a case-control study of Chinese women, we examined whether these polymorphisms were associated with risk of breast cancer and fi ...[more]

PMID: 17624589

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Project description:BackgroundGlutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population.MethodsWe analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr).ResultsThe GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively).ConclusionsThis study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed.

Project description:Glutathione S-transferase (GST) genes as well as heme oxygenase 1 gene (HMOX1) encode enzymes that detoxify carcinogens and protect against oxidative stress. This study was undertaken to examine the impact of gene-smoking interactions on susceptibility to rheumatoid arthritis (RA).Caucasian patients with RA and matched control subjects (n = 549 each) were selected from the Nurses' Health Study. Genotyping of the patients' blood by TaqMan and BioTrove assays identified homozygous deletions at the M1 and T1 loci of GST (GSTM1-null and GSTT1-null, respectively) as well as alleles for GSTP1 (rs1695) and HMOX1 (rs2071746). In addition, the effect of gene-smoking interactions on the risk of all RA and RA serologic phenotypes was studied in separate logistic models that were adjusted for covariates. Multiplicative interactions were assessed by including a product term in a logistic model, and additive interactions were assessed using the attributable proportion (AP) due to interaction. For replication of the results, analyses revealing significant interactions were repeated in an independent case-control cohort from the Epidemiological Investigation of Rheumatoid Arthritis study.For the risk of all RA, multiplicative (P = 0.05) and additive (AP = 0.53, P = 0.0005) interactions between the GSTT1-null polymorphism and smoking and multiplicative interactions (P = 0.05) between HMOX1 and smoking were observed. For the risk of seropositive RA, multiplicative (P = 0.01) and additive (AP = 0.62, P < 0.0001) interactions between GSTT1-null and smoking and additive interactions (AP = 0.41, P = 0.03) between HMOX1 and smoking were observed. After correction for multiple comparisons, the additive interactions between GSTT1-null and smoking remained significant. The M1-null and P1 variants of GST did not show significant interactions, and no associations with seronegative RA were observed. In replication analyses, significant multiplicative interactions (P = 0.04) and additive interactions (AP = 0.32, P = 0.02) were observed between GSTT1-null and smoking in the risk of anti-citrullinated protein antibody-positive RA.Significant gene-environment interactions between the GSTT1-null polymorphism and heavy smoking were observed when assessing the risk of RA. Future studies are needed to assess the impact of these interactions on RA prediction.

Dataset Information

Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women.

Publications

Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women.

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