title: Effects of glutathione-S-transferase polymorphisms on the risk of breast cancer: a population-based case-control study in Pakistan.
abstract: Cancer is widely accepted as one of the major health issues. Diet composition and exposure to environmental genotoxic and carcinogenic agents such as polycyclic aromatic hydrocarbons (PAHs) are among the causative factors for various types of cancers, including breast cancer. Low penetrance genes including glutathione S transferases (GST) in association with environmental factors can contribute greatly in the development of breast cancer. We were interested to investigate the association of the polymorphisms of GSTM1, GSTT1, GSTP1 and GSTO2 with the risk of breast cancer in the Pakistani population. One hundred women visiting the Department of Radiology and Oncology, Nishter Hospital, Multan with pathologically confirmed breast cancer, and 100 healthy volunteers from central Pakistan were enrolled in the present study. The strength of the association of various factors with breast cancer was measured by calculating odd ratios (ORs) which were determined by logistic regression. All P values cited are two-sided; differences resulting in a P value of less or equal to 0.05 were declared statistically significant. The Hardy Weinberg equilibrium was tested for the genotype proportions in the control group, as a measure of quality control. Those aged 36-45, in menopause or with a history of cancer in the family had a significantly higher prevalence of breast cancer compared with controls. The frequency of GSTM1 and GSTT1 was similar in both control and patients suggesting no association with the risk of cancer development, however GSTM1 and GSTT1 were significantly linked with the risk of breast cancer in smokers and in women with a history of breast cancer in the family respectively. Similarly women homozygous for GSTP1 or GSTO2 and with a history of breast cancer, or in menopause, were at greater risk of breast cancer than wild type or heterozygotes. Our data suggest that genetic differences in some GST genes may be linked with an increased susceptibility to breast cancer. Furthermore it also gives an insight into the interaction between the GST polymorphisms and pre-menopausal diagnosis of breast cancer.
authors: Institute of Molecular Biology & Biotechnology, Bahauddin Zakariya University, Multan 60800, Pakistan. sohail82_2@yahoo.com
authors: Asma
authors: A
authors: Sohail
authors: Nazia
authors: N
authors: Kanwal
authors: Muhammad
authors: M
authors: Ali
authors: Sobia
authors: S
authors: Sadia
authors: Ahmed Ijaz
authors: AI
authors: Masood
authors: Faheem
authors: F
authors: Ali
authors: Furhan
authors: F
authors: Iqbal
authors: Neil
authors: N
authors: Crickmore
authors: Rehan Sadiq
authors: RS
authors: Shaikh
authors: Ali H
authors: AH
authors: Sayyed
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D010154:Pakistan; D019683:Penetrance; D011110:Polymorphism, Genetic; D017697:Premenopause / Q000235:genetics; D012907:Smoking / Q000235:genetics
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C492569:GSTO2 protein, human