Protein carbonyl levels, glutathione S-transferase polymorphisms and risk of colorectal cancer

Abstract

Oxidative stress has been associated with the carcinogenesis of colorectal cancer. Glutathione S-transferases (GSTs) modulate the elimination of free radical. We conducted a case-control study to examine the interaction between oxidative stress and GSTs polymorphisms on colorectal cancer risk. This study recruited 727 pathologically confirmed colorectal adenocarcinoma cases and 736 sex- and age-matched controls. Plasma protein carbonyls, as a parameter of oxidative stress, were measured using enzyme-linked immunosorbent assay. Genotypes of GSTM1, GSTT1 and GSTP1 genes were determined using polymerase chain reaction methods. The protein carbonyl levels were significantly higher in cases than in controls and exerted a dose-response relationship (P for trend < 0.001). Compared with the first carbonyl quartile subjects, those in the second, third and fourth quartiles had odds ratios (ORs) of 1.54 [95% confidence interval (CI) = 1.13-2.10], 1.52 (95% CI = 1.11-2.07) and 1.98 (95% CI = 1.46-2.67), respectively. This effect was significantly modified by GSTM1 genotype (P for interaction = 0.037). The three-way interaction analysis revealed that interactions between GSTM1 genotype and cigarette smoking and between GSTT1 genotype and alcohol drinking further modified the oxidative stress contribution for colorectal cancer (p for interaction were 0.067 and 0.054, respectively). The impact of oxidative stress was more prominent among ever-smokers with GSTM1-null genotype (OR = 3.45, 95% CI = 1.70-6.97) and ever-drinkers with GSTT1-present genotype (OR = 3.87, 95% CI = 1.82-8.25). Our results indicate that interaction between oxidative stress and GSTs polymorphisms may play an important role in the pathogenesis of colorectal cancer.

Oxidative Protein Damage with Carbonyl Levels and Nitrotyrosine Expression after Chemotherapy in Bone Marrow Transplantation Patients

“…Because proteins have many different and unique biological functions, oxidative modifications of the proteins can lead to diverse functional consequences. Their enzymatic and binding activities may be inhibited, their susceptibility to aggregation and proteolysis may be increased, and their uptake by the cells may be increased or decreased in addition to their altered immunogenicity [3,6,7,14]. …”

“…Carbonyl groups are introduced into proteins by various oxidative pathways. ROS can react directly with the proteins, or they can react with molecules such as sugars and lipids, generating products (reactive carbonyl species) that may react with proteins and lead to the formation of protein carbonyl derivatives [2,3,4,5,6,7]. …”

Nutrigenetics and Modulation of Oxidative Stress

“…In the GSTP1 gene, several polymorphisms have been identified, including a non-synonymous-coding polymorphism resulting in a isoleucine to valine amino acid change at codon 105 (Ile105Val) and an alanine to valine amino acid change at codon 114 (Ala114Val) [57]. While one study showed levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine to differ by GSTP1 but not GSTM1 or GSTT1 genotypes [58], another found no differences in protein carbonyl levels by any GST genotype [59]. …”

GSTM1 and GSTT1 polymorphisms and colorectal cancer risk in Chinese population: a meta-analysis

“…According to the exclusion criteria, 13 publications were excluded including nine articles containing overlapping data [20][21][22][23][24][25][26][27][28], two about colorectal adenoma [29,30], one for being case-only study [31], and one for not about GSTT1 or GSTM1 polymorphism [32]. At last, data were available from 19 individual casecontrol studies [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] (a total of 3,130 CRC cases and 6,423 controls). Seventeen studies on GSTM1 polymorphism (a total of 2,987 CRC cases and 6,240 controls), 12 studies on GSTT1 polymorphism (a total of 2,509 CRC cases and 5,744 controls), and seven studies on GSTM1-GSTT1 interaction analysis (a total of 1,214 CRC cases and 4,189controls) were included in the meta-analysis.…”

“…These 19 individual case-control studies were published from 1996 to 2010 with six in English [33,34,41,45,50,51] and 13 in Chinese [35-40, 42-44, 46-49]. Table 1 presents a brief description of these 19 case-control studies.…”