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Study highlights Gene-environment interactions between GSTs polymorphisms and targeted epigenetic alterations in hepatocellular carcinoma following organochlorine pesticides (OCPs) exposure

Although usage of organochlorine pesticides (OCPs) has been banned in most countries, residues of HCHs and DDTs still exist in various environmental matrices owing to their environmental persistence and long-range transport. General population remain extensively exposed to them via the diet. OCPs are classified as carcinogens, and associated with elevated risk of hepatocellular carcinoma (HCC). Given that the liver is a target organ for OCPs and it is susceptible to OCPs-induced injury, the detoxifying abilities of liver GSTs plays a key role in OCPs-induced ROS and inflammation. Therefore, OCPs exposure and GSTs detoxification could interact in HCC development risk. However, the interplay between environmental risk factors OCPs exposure and polymorphic tumour suppressor GSTs genes or epigenetic factors in HCC development remains ambiguous.

Recently, in the study published in Environment International, Dr. TIAN Meiping from Institute of Urban Environment, Chinese Academy of Sciences and collaborators Prof. SHEN Heqing’s group from Xiamen University and Prof. Martin s group from University of Central Lancashire revealed the gene-environment interactions in the multifactorial development of HCC.

The researchers employed a gas chromatography coupled with mass selective detector (GC-MS) to detect the 8 congeners of OCPs, and applied high-resolution melting PCR (HRM PCR) and DNA sequencing to determine 3 subtypes of GSTs polymorphisms and epigenetic alterations in the Chinese HCC case-control population.

The data in this study revealed that serum OCPs concentrations in HCC cases were significantly higher than those in controls, GSTP1 methylation is significantly associated with elevated risk of HCC, while no significance is observed for GSTs polymorphisms. Moreover, the effects of OCPs exposure on HCC risk are more pronounced amongst GSTP1 (Ile/Val+Val/Val) and GSTP1 promoter methylation subjects than those who were GSTP1 (Ile/Ile) and unmethylated subjects. The interactions between OCPs exposure and GSTP1 genotype as well as GSTP1 epigenetic status are statistically significant.

The plausible interaction mechanism is that individuals with GSTP1 (Ile/Val+Val/Val) or GSTP1 promoter methylation status cause enzyme function impaired or lost then effect OCPs detoxification metabolism, resulting in increased the OCPs-exposed HCC risk. The study provides supportive evidence that GSTP1 might affect susceptibility to OCPs exposure related to HCC development risk, and may benefit for susceptible population early prevention.

This work is financially supported by the Nature Science Foundation of Fujian Province, the National Natural Science Foundation of China, and the Crossing-Group Project of KLUEH.


Schematic illustration of the environmental risk factors OCPs exposure and tumour suppressor genes GSTP1 polymorphsim or epigenetic modification in HCC development

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