Abstract

Glutathione S-transferase (GST) enzymes are responsible for cellular detoxification of many carcinogens and are important anticancer elements. This study assessed potential relationships between GSTM1, GSTT1, and GSTP1 polymorphisms and colorectal cancer (CRC) risk in Polish nonsmokers. We also analyzed the influence of GST gene polymorphisms on CRC clinical and histopathological features. Our study included 197 CRC patients and 104 healthy controls. GSTM1, GSTT1, and GSTP1 polymorphisms were evaluated using qPCR. Polymorphism frequencies observed in our control group corresponded to those in other European populations. The GSTM1 null and GSTT1 null genotypes were observed with similar frequencies in both CRC patients and controls (GSTM1 null: 46.7% vs. 45.2%; GSTT1 null: 15.7% vs. 20.2%). GSTP1 Ile/Ile, Ile/Val, and Val/Val genotype frequencies were respectively 42.1%, 48.2%, and 9.6% in patients and 48.1%, 42.3%, and 9.6% in controls. GSTT1 polymorphism correlated with higher tumor grade in CRC patients, and the GSTM1 null/null genotype was associated with more frequent metastasis to lymph nodes (pN classification). Our results suggest that GST gene polymorphisms may influence CRC tumor grade and stage.

Highlights

  • In Poland in 2013, colorectal cancers (CRC) were the third most common cancers in males (8,726 cases, 11.2% of all cases) and the second most common in females (7,173 cases, 9.2% of all cases)

  • GSTT1 polymorphism correlated with higher tumor grade in CRC patients, and the GSTM1 null/null genotype was associated with more frequent metastasis to lymph nodes

  • Our results suggest that Glutathione S-transferase (GST) gene polymorphisms may influence CRC tumor grade and stage

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Summary

Introduction

In Poland in 2013, colorectal cancers (CRC) were the third most common cancers in males (8,726 cases, 11.2% of all cases) and the second most common in females (7,173 cases, 9.2% of all cases). CRC causes include heterogeneous, controllable, and external factors related to lifestyle, such as diet and socioeconomic standing [2]. Such factors include high consumption of red meat, insufficient intake of fiber, vitamins, and minerals (calcium, selenium, zinc, copper, manganese, folic acid), excessive fat consumption, obesity, and lack of exercise. An extensive meta-analysis conducted in 2017 based on eight studies, 103 articles, and approximately 900,000 cases assessed the risk of CRC development in relation to the inflammatory dietary index (DII). Glutathione S-transferases are believed to play roles in deactivating pathogenic compounds and allergens during phase II of biotransformation

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