GSTM1 and GSTT1 polymorphisms and postmenopausal breast cancer risk

Wei Zheng, Wan Qing Wen, Deborah R. Gustafson, Myron Gross, James R Cerhan, Aaron R. Folsom

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Glutathione S-transferases (GSTs) are a family of important enzymes involved in the detoxification of a wide variety of known and suspected carcinogens, including potential mammary carcinogens identified in charred meats and tobacco smoke. A substantial proportion of the Caucasian population has a homozygous deletion (null) of the GSTM1 or GSTT1 gene, which results in lack of production of these isoenzymes. We conducted a case-control study in a cohort of postmenopausal Iowa women who in 1986 completed a mailed questionnaire on lifestyle factors including information on cigarette smoking and breast cancer risk factors. DNA samples and information related to charred meat intake were obtained, in the case-control study, from breast cancer cases diagnosed during 1992-1994, and a random sample of cancer-free cohort members. Included in this study were 202 cases and 481 controls who were genotyped for GSTM1 or GSTT1 gene polymorphisms. Compared to women who had both GSTM1 and GSTT1 genes, a 60% elevated risk (95% CI = 1.0-2.5) was observed among those whose GSTM1 or GSTT1 gene was deleted. When stratified by meat eating habits, the risk of breast cancer associated with null GSTM1 or GSTT1 genotype was observed primarily among women who ate meats consistently well- or very well-done. Women who carried either one of the null genotypes and consumed meat consistently well- or very well-done had a 3.4-fold elevated risk of developing breast cancer (95% CI = 1.6-7.1). Cigarette smoking was not a risk factor for breast cancer among women who had either the GSTM1 or GSTT1 genes. Among those with the null GSTT1 genotype, however, a significantly elevated risk of breast cancer was associated with cigarette smoking (OR = 2.5, 95% CI = 1.1-5.4) and the association was stronger among former (OR = 4.4, 95% CI = 1.5-12.8) than current smokers (OR = 1.3, 95% CI = 0.4-4.1). This study suggests that certain null GST genotypes may be associated with an elevated risk of breast cancer and the association may be modified by charred meat intake and cigarette smoking.

Original languageEnglish (US)
Pages (from-to)9-16
Number of pages8
JournalBreast Cancer Research and Treatment
Volume74
Issue number1
DOIs
StatePublished - 2002

Fingerprint

Meat
Breast Neoplasms
Smoking
Genotype
Genes
Glutathione Transferase
Carcinogens
Case-Control Studies
Feeding Behavior
Smoke
Isoenzymes
Tobacco
Life Style
Breast
DNA
Enzymes
Population
Neoplasms

Keywords

  • Breast neoplasms
  • Diet
  • Etiology
  • Genetic susceptibility
  • Smoking

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

GSTM1 and GSTT1 polymorphisms and postmenopausal breast cancer risk. / Zheng, Wei; Wen, Wan Qing; Gustafson, Deborah R.; Gross, Myron; Cerhan, James R; Folsom, Aaron R.

In: Breast Cancer Research and Treatment, Vol. 74, No. 1, 2002, p. 9-16.

Research output: Contribution to journalArticle

Zheng, Wei ; Wen, Wan Qing ; Gustafson, Deborah R. ; Gross, Myron ; Cerhan, James R ; Folsom, Aaron R. / GSTM1 and GSTT1 polymorphisms and postmenopausal breast cancer risk. In: Breast Cancer Research and Treatment. 2002 ; Vol. 74, No. 1. pp. 9-16.
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