The Investigation of Relationship between the Poly-Morphism in Exon 5 of Glutathione S-Transferase P1 (Gstp1) Gene and Breast Cancer

Abstract

Beside environmental factors, genetic factors have an important place in the etiology of breast cancer which is one of the most common worldwide and highest mortality cancers among women. Breast cancer is associated with different types of somatic genetic alterations such as mutations in oncogenes and tumor suppressor genes. Glutathione S-transferases (GSTs) are a superfamily of enzymes that are potentially important in regulating susceptibility to cancer because of their ability to metabolize reactive electrophilic intermediates to usually less reactive and more water soluble glutathione conjugates. In GSTP1 (chromosome 11q13), an amino acid transition has been reported at codon 105 (Ile105Val), leading to expression of an active but functionally different protein. The aim of this study was to investigate the frequencies of Ile105Val polymorphism in the exon 5 of GSTP1 gene and its effect on the risk of developing breast cancer in a Mersin sample of the Turkish population. In addition, we investigated whether an association exists between breast cancer and other risk factors including age at menarche, age at menopause, smoking, BMI, and family history.

Our study group consisted of 167 individuals, of whom 99 were healthy women controls and 68 breast cancer cases. The experimental group was comprised of women who had been diagnosed with breast cancer at the Department of Medical Oncology, Mersin University, Turkey. Controls were selected by taking age and sex variable into consideration. Genomic DNA from breast cancer patients and control subjects was analyzed by PCR-RFLP.

For the exon 5 of GSTP1 gene, the distribution of AA and GG genotypes in the Mersin sample of the Turkish population were 64% and 4% in control group, whereas this genotype distribution were 58% and 7% in patients, respectively. Putative risk factors including age, body mass index or family history were found to be correlated with the developing breast cancer. However, it was determined that smoking, menarch age and menopause status were not associated with breast cancer risk.