GSTM1 and GSTT1 Genetic Polymorphisms and Breast Cancer Risk in Selected Filipino Cases

Abstract

Background: The association of genetic polymorphisms with cancer development has been shown to be race- and tumor site-specific. Thus, this study aimed to determine whether polymorphisms in the GSTM1 and GSTT1 genes are associated with breast cancer among selected Filipinos. Methods: A total of 136 histologically confirmed breast cancer cases were age- and sex-matched with 136 clinically healthy controls. Genomic DNA extracted from blood samples of participants were screened for GSTM1 and GSTT1 genetic polymorphisms by multiplex PCR. Results: The frequency of null genotypes among the cases (GSTM1: n=78; 57.4%; GSTT1: n=61; 44.9%) was not significantly different (p>0.05) from the controls (GSTM1: n=93; 68.4%; GSTT1: n=59; 43.4%). It was also demonstrated that risk for breast cancer was increased in passive smokers carrying the GSTM1 null (OR=2.56; 95% CI=1.38-4.75) or GSTT1 positive (OR=2.00; 95% CI=1.05-3.83) genotypes. Moreover, risk was decreased in alcohol users carrying the GSTT1 null (OR=0.39; 95% CI=0.16-0.97) genotype. Conclusion: This study suggests that variants of GSTM1 and GSTT1 may not be risk factors for breast cancer development among Filipinos. However, the risk may be increased when these genotypes were combined with lifestyle or environmental factors.

Keywords: Breast cancer; GSTM1; GSTT1; genetic polymorphism.

Figure 1

Representative Results for (a) GSTM1 and (b) GSTT1 Genotyping by PCR Method. DNA isolates from breast cancer cases and controls were subjected to duplex PCR using GSTM1, GSTT1, and albumin primers. (a) GSTM1. Cases: Lane M: marker; lanes 5, 7 to 9, and 11: GSTM1 null; lanes 1 to 4, 6, 10, and 12: GSTM1 positive; lane 13: negative control. Controls: lanes 1, 2, 5, and 8 to 12: GSTM1 null; lanes 3, 4, 6, and 7: GSTM1 positive. (b) GSTT1. Cases: Lane M: marker; lanes 1, 2, 7, 8, and 10 to 12: GSTT1 null; lanes 3 to 6 and 9: GSTT1 positive; lane 13: negative control. Controls: lanes 7, 9, and 10: GSTT1 null; lanes 1 to 6, 8, 11, and 12: GSTT1 positive

Figure 2

Comparison of GSTM1 and GSTT1 Genotype Frequencies. Frequencies were determined from the distribution of the positive and null genotypes of GSTM1 and GSTT1 to breast cancer cases and controls. (a) The frequencies of the GSTM1 positive genotype for cases and controls were 42.6% (n=58) and 31.6% (n=43), respectively, while the frequencies of the GSTM1 null genotype for cases and control were 57.4% (n=78) and 68.4% (n=93), respectively. (b) The frequencies of the GSTT1 positive genotype for cases and controls were 55.1% (n=75) and 56.6% (n=77), respectively, while the frequencies of the GSTT1 null genotype for cases and control were 44.9% (n=61) and 43.4% (n=59), respectively