The Glutathione Biotransformation System and Colorectal Cancer Risk in Humans

Grubben, M.J.A.L.; Nagengast, Fokko M.; Katan, Martijn B.; Peters, Wilbert H.M.

doi:10.1080/003655201753265479

Cited by 38 publications

(26 citation statements)

References 54 publications

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“…GSTP1 has a polymorphic site at codon 105 (exon 5), where an A to G transition causes an Ile to Val substitution (Ile105Val), resulting in lower enzyme activity to variety of electrophilic molecules (Millar et al, 1999;Hayes et al, 2005;McIlwain et al, 2006). Numerous reports assessed the risk of colorectal cancer development in subjects carrying the variant Val GSTP1 allele; however, the results are controversial (Harries et al, 1997;Welfare et al, 1999;Kiyohara, 2000;Grubben et al, 2001;Loktionov et al, 2001;Seow et al, 2002;Ates et al, 2005;Sun et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

The GSTP1 Ile105Val Polymorphism is not Associated with Susceptibility to Colorectal Cancer

Khabaz

2012

Asian Pacific Journal of Cancer Prevention

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The glutathione S transferase (GST) family is a major part of cellular defense mechanisms against endogenous and exogenous substances, many of which have carcinogenic potential. Alteration in the expression level or structure of the glutathione-S-transferase (GST) enzymes may lead to inadequate detoxification of potential carcinogens and consequently contribute to cancer development. A member of the glutathione-S-transferase (GST) family, GSTP1, is an attractive candidate for involvement in susceptibility to carcinogen-associated colorectal cancer. An AgG transition in exon 5 resulting in an Ile105Val amino acid substitution has been identified which alters catalytic efficiency. The present study investigated the possible impact of Ile105Val GSTP1 polymorphism on susceptibility to colorectal cancer. in Jordan We examined 90 tissue samples previously diagnosed with colorectal carcinoma, and 56 non-cancerous colon tissues. DNA was extracted from paraffin embedded tissues and the status of the GSTP1 polymorphism was determined using a polymerase chain reaction restriction fragment length polymorphism (RFLP) method. No statistically significant differences were found between colorectal cancer cases and controls for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. The glutathione S-transferase polymorphism was not associated with risk in colorectal cancer cases in Jordan stratified by age, sex, site, grade or tumor stage. In conclusion, the GSTP1 Ile105Val polymorphism is unlikely to affect the risk of colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

The GSTP1 Ile105Val Polymorphism is not Associated with Susceptibility to Colorectal Cancer

Khabaz

2012

Asian Pacific Journal of Cancer Prevention

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“…GSTs catalyse this detoxification via the conjugation of carcinogens with GSH. Low GST activity has been correlated with a higher tumour incidence in the colonic mucosa [234]. Studies in humans have demonstrated that Brassica vegetables consumption can increase GST levels and activity in addition to GSH levels in lymphocytes.…”

Section: Phase I and Phase Ii Enzyme Activities Andmentioning

confidence: 99%

Glucosinolates inBrassicavegetables: The influence of the food supply chain on intake, bioavailability and human health

Verkerk¹,

Schreiner

Krumbein

et al. 2009

Molecular Nutrition Food Res

527

424

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Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.

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“…Results from both animal models and clinical investigations continue to suggest that this family of enzymes plays a pivotal role in cancer susceptibility and cancer prevention. Individuals deficient in the protection afforded by this family of enzymes are at increased risk of cancer (2)(3)(4). Induction of these enzymes by either naturally occurring or synthetic agents represents a promising chemopreventive strategy (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Human Glutathione S-Transferases by Polyphenon E Intervention

Chow¹,

Hakim²,

Vining³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Purpose: Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Induction of detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer-preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea polyphenol administration on a major group of detoxification enzymes, glutathione S-transferases (GST). Methods: A total of 42 healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, a fasting blood sample was collected, and plasma and lymphocytes were isolated for assessment of GST activity and level. Following the baseline evaluation, study participants underwent 4 weeks of green tea polyphenol intervention in the form of a standardized Polyphenon E preparation at a dose that contains 800 mg epigallocatechin gallate (EGCG) once a day. Polyphenon E was taken on an empty stomach to optimize the oral bioavailability of EGCG. Upon completion of the intervention, samples were collected for postintervention GST assessment. Results: Four weeks of Polyphenon E intervention enhanced the GST activity in blood lymphocytes from 30.7 F 12.2 to 35.1 F 14.3 nmol/min/mg protein, P = 0.058. Analysis based on baseline activity showed that a statistically significant increase (80%, P = 0.004) in GST activity was observed in individuals with baseline activity in the lowest tertile, whereas a statistically significant decrease (20%, P = 0.02) in GST activity was observed in the highest tertile. In addition, Polyphenon E intervention significantly increased the GST-P level in blood lymphocytes from 2,252.9 F 734.2 to 2,634.4 F 1,138.3 ng/mg protein, P = 0.035. Analysis based on baseline level showed that this increase was only significant (P = 0.003) in individuals with baseline level in the lowest tertile, with a mean increase of 80%. Repeated Polyphenon E administration had minimal effects on lymphocyte GST-M and plasma GST-A levels. There was a small but statistically significant decrease (8%, P = 0.003) in plasma GST-A levels in the highest tertile. Conclusions: We conclude that 4 weeks of Polyphenon E administration resulted in differential effects on GST activity and level based on baseline enzyme activity/level, with GST activity and GST-P level increased significantly in individuals with low baseline enzyme activity/level. This suggests that green tea polyphenol intervention may enhance the detoxification of carcinogens in individuals with low baseline detoxification capacity. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1662 -6)

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The Glutathione Biotransformation System and Colorectal Cancer Risk in Humans

Cited by 38 publications

References 54 publications

The GSTP1 Ile105Val Polymorphism is not Associated with Susceptibility to Colorectal Cancer

The GSTP1 Ile105Val Polymorphism is not Associated with Susceptibility to Colorectal Cancer

Glucosinolates inBrassicavegetables: The influence of the food supply chain on intake, bioavailability and human health

Modulation of Human Glutathione S-Transferases by Polyphenon E Intervention

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