ARKOM CHEIRSILPA2, MATI RIENKIJKARN
2Medical Oncology Division, National Cancer Institute, Rama VI road,
Ratchatewi, Bangkok10400, Thailand
Background: Breast cancer is the most prevalent cancer among women,
in Thialnd, breast cancer is the second leading cancer among women. Individual
cancer risk depends on various factors, including detoxification of carcinogens.
The glutathione S-transferase supergene family is an important part of cellular
enzymatic defense against endogenous and exogenous chemicals. Many studies have
shown a possible link with the null GSTM1 genotype and susceptibility to cancer,
however, most studies reported the weakly positive or negative finding. It is
increasing recognized that the high degree of individual variability in the
susceptibility to cancer may be influenced by complex gene-environment interaction,
where several genes and exposure work interactively. We examined p53 protein
accumulation in relation to GSTM1 null genotype.
Methods: In this study, deletion polymorphism in the GSTM1 gene was investigated
in relation to breast cancer risk in 295 breast cancer patients and 227 controls.
The GSTM1 genotype were performed by PCR. p53 protein accumulation were detected
in breast tissues by immunohistochemistry.
Results: The frequency of homozygous null GSTM1 genotype in control and
breast cancer groups were 64.7% and 61.4%, respectively, there was no statistically
different between cases and controls (p =0.24). An association was
observed between the GSTM1 null genotype and p53 accumulation, with patients
carrying the GSTM1 null genotype more frequently having p53 alteration compared
with patients with GSTM1 wild type (73.7% versus 26.3%, p =0.053).
Among smokers, GSTM1 null genotype was not associate with the increase risk
of breast cancer (p =0.103), however, cases with GSTM1 null genotype
had tumor with altered p53 more frequently than did cases with GSTM1 wild type
(p =0.059). A similar results was observed among patients who drink
alcohol (p =0.09)or who use oral contraceptive (p =0.013).
Conclusion: Many genes and environmental exposures contribute to the carcinogenic
process. The result suggested that GSTM1 may play a role in breast tumorigenesis
through a pathway that involves abnormalities in the p53 tumor suppressor gene.
Key Words: GSTM1 null genotype, p53 expression, breast cancer, risk
ที่มา ABSTRACT นำเสนอที่ การประชุมวิชาการสมาคมพิษวิทยาแห่งประเทศไทย
ประจำปี 2547 อาหารกับความปลอดภัย วันศุกร์ที่ 17 ธันวาคม 2547 โรงแรมมิราเคิลแกรนด์