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No Apparent Association of GSTP1 A³¹³G Polymorphism with Breast Cancer Risk among Postmenopausal Iowa Women¹

Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-8300 [M. Z., W-Q. W., W. Z.]; Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina [R. L.]; Department of Nutrition and Food Sciences, Utah State University, Logan, Utah 84322-8700 [D. R. G.]; and Department of Health Science Research, Mayo Clinic Cancer, Rochester, Minnesota 55905 [J. R. C.]

	Introduction

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GSTP1³ catalyzes the conjugating reactions of PAHs and their electrophilic compounds to facilitate their excretion (1) . Burned foods and cigarette smoke contain mammary carcinogens such as PAHs (2) . Mice treated with PAHs had an elevated risk of skin tumors, particularly among those without the GSTP1 gene (3) . The expression of the GSTP1 gene has been observed in many human tissues including breast epithelium (4) .

A polymorphic adenine to guanine transition at nucleotide 313 (A³¹³G) in exon 5 results in an isoleucine to valine substitution in codon 105 (I¹⁰⁵V) (5) . This codon is located in the substrate-binding site of GSTP1, and the corresponding allozymes exhibited differential catalytic activities toward diverse substrates (5) . Epidemiological studies associating GSTP1 polymorphism with breast cancer risk are few and inconsistent (6 , 7) . To evaluate the role of this polymorphism and its joint effect with PAH exposure in the risk of breast cancer, we analyzed data from a case-control study conducted among postmenopausal women in Iowa.

	Materials and Methods

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A nested case-control study of breast cancer was conducted within the Iowa Women’s Health Study, a prospective cohort study of 41,836 postmenopausal Caucasian women who completed a self-administered baseline questionnaire in January 1986. A supplementary survey on meat-eating habit was completed during 1995 to 1996 in 273 breast cancer cases diagnosed during 1992 to 1994 and 657 women randomly selected from the cohort members without any cancer diagnosis in 1992. Of them, blood samples were obtained from 488 women (156 cases and 332 controls). Genomic DNA from peripheral white blood cells was used to determine the genotypes of the GSTP1 gene using the PCR-RFLP method. The primers for the PCR reactions were GSTP1 forward 5'-ccagtgactgtgtgttgatc-3' and reverse 5'-caaccctggtgcagatgctc-3'. The PCR reactions were carried out in a 50-µl mixture containing sample DNA, 20 mM Tris-HCl (pH 8.4), 5.0 mM KCl, 1.5 mM MgCl₂, 0.2 mM deoxynucleotide triphosphate 1 unit of Taq polymerase, and 0.4 µM of each oligonucleotide primer. Amplification, which resulted in a 189-bp fragment, was achieved by 35 cycles of 30 s at 94°C, 30 s at 62°C, and 30 s at 72°C. At the end, the reactions were extended for 7 min at 72°C. Each PCR product (5 µl) was subjected to BsmAI digestion and analyzed by gel electrophoresis (3% 2:1 Nosier/SeaKem agarose). The presence of the polymorphic BsmAI restriction site yields 148- and 41-bp fragments, indicating the presence of the G allele.

ORs and their 95% CIs were derived from unconditional logistic regression models and were adjusted for potential confounding variables. Trend tests for dose-response across levels of the exposure variables were performed by treating ordinal-score variables as continuous variables in logistic regression models. Reported Ps are based on two-sided probability tests, with a significance level of P < 0.05.

	Results

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The frequency of the variant allele was 29%, consistent with that reported from a previous study (7) . There is no statistical significant association between A³¹³G polymorphism and breast cancer risk (Table 1) . This polymorphism was not found to modify the association of well-done meat intake or cigarette smoking with breast cancer risk.

	Discussion

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One potential concern of the study may be its low response rate. However, it is unlikely that selection bias can explain the null association, because the GSTP1 genotype was unlikely to be associated with study participation.

Our study has an 80% statistical power to detect an OR of 1.74 for the GSTP1 AG and GG genotypes compared with the AA genotype at the significance level of 0.05. The statistical power to examine the interaction was further limited. Nevertheless, this study showed that there was no apparent association of GSTP1 polymorphism with breast cancer risk, and the modifying effect of GSTP1 polymorphism, if any, on the association of well-done meat intake and smoking with breast cancer risk was unlikely to be substantial.

	Footnotes

 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported in part by USPHS Grant RO1CA39742 from the NIH and by Supplementary Grant OWH-284 from the National Action Plan on Breast Cancer, Office on Women’s Health, Public Health Service.

² To whom requests for reprints should be addressed, at Vanderbilt University Medical Center, Center for Health Services Research, Medical Center East, 6^th Floor, Nashville, TN 37232-8300. Phone: (615) 936-0682; Fax: (615) 936-1269; E-mail: Wei.Zheng{at}mcmail.vanderbilt.edu

³ The abbreviations used are: GSTP1, glutathione S-transferase ; OR, odds ratio; CI, confidence interval; PAH, polycyclic aromatic hydrocarbon.

Received 3/12/01; revised 7/27/01; accepted 10/ 1/01.

	References

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