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Association between glutathione S-transferase T1, M1, and P1 genotypes and the risk of colorectal cancer.

Cong N, Liu L, Xie Y, Shao W, Song J - J. Korean Med. Sci. (2014)

Bottom Line: Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens.Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods.In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong, China.

ABSTRACT
Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P heterozygous=0.790 or P variant=0.261). Furthermore, individuals who simultaneously carried the genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.

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Related in: MedlinePlus

Representative genotyping result. Lane 1: DNA marker. Lane 2: GSTT1 non-, GSTM1 non- (459 bp, 268 bp, 219 bp). Lane 3: GSTT1 non-, GSTM1  (459 bp, 268 bp). Lane 4: GSTT1 , GSTM1 non- (268 bp, 219 bp). Lane 5: GSTT1 , GSTM1  (268 bp). Lane 6: GSTP1 Ile/Ile (329 bp, 104 bp). Lane 7: GSTP1 Val/Val (222 bp, 107 bp, 104 bp). Lane 8: GSTP1 Ile/Val (329 bp, 222 bp, 107 bp, 104 bp).
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Figure 1: Representative genotyping result. Lane 1: DNA marker. Lane 2: GSTT1 non-, GSTM1 non- (459 bp, 268 bp, 219 bp). Lane 3: GSTT1 non-, GSTM1 (459 bp, 268 bp). Lane 4: GSTT1 , GSTM1 non- (268 bp, 219 bp). Lane 5: GSTT1 , GSTM1 (268 bp). Lane 6: GSTP1 Ile/Ile (329 bp, 104 bp). Lane 7: GSTP1 Val/Val (222 bp, 107 bp, 104 bp). Lane 8: GSTP1 Ile/Val (329 bp, 222 bp, 107 bp, 104 bp).

Mentions: Genomic DNA was extracted from the blood samples obtained using EasyPure Blood Genomic DNA Kit (TransGen Biotech, Beijing, China). The GSTT1 and GSTM1 polymorphisms were genotyped by using multiplex polymerase chain reaction (PCR) technique with the beta-globin gene served as the internal control. The primers used for GSTT1 genotyping were 5'-TTCCTTACTGGTCCTCACATCTC-3' and 5'-TCACCGGATCATGGCCAGCA-3', which produced a fragment of 459 bp. On the other hand, the primers used for GSTM1 genotyping were 5'-GAACTCCCTGAAAAGCTAAAGC-3' and 5'-GTTGGGCTCAAATATACGGTGG-3', which produced a fragment of 219 bp. The 268 bp beta-globin gene was amplified by using 5'-CAACTTCATCCACGTTCACC-3' and 5'-GAAGAGCCAAGGACAGTTAC-3' primers. The multiplex PCR was performed under the following conditions: 5 min of initial denaturation at 94℃, followed by 35 cycles of 1 min at 94℃, 30 sec at 56℃, 45 sec at 72℃, and a final extension for 5 min at 72℃. The PCR products were separated on 3% agarose gels for visualization of the bands for inferring of the genotypes (Fig. 1).


Association between glutathione S-transferase T1, M1, and P1 genotypes and the risk of colorectal cancer.

Cong N, Liu L, Xie Y, Shao W, Song J - J. Korean Med. Sci. (2014)

Representative genotyping result. Lane 1: DNA marker. Lane 2: GSTT1 non-, GSTM1 non- (459 bp, 268 bp, 219 bp). Lane 3: GSTT1 non-, GSTM1  (459 bp, 268 bp). Lane 4: GSTT1 , GSTM1 non- (268 bp, 219 bp). Lane 5: GSTT1 , GSTM1  (268 bp). Lane 6: GSTP1 Ile/Ile (329 bp, 104 bp). Lane 7: GSTP1 Val/Val (222 bp, 107 bp, 104 bp). Lane 8: GSTP1 Ile/Val (329 bp, 222 bp, 107 bp, 104 bp).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4234915&req=5

Figure 1: Representative genotyping result. Lane 1: DNA marker. Lane 2: GSTT1 non-, GSTM1 non- (459 bp, 268 bp, 219 bp). Lane 3: GSTT1 non-, GSTM1 (459 bp, 268 bp). Lane 4: GSTT1 , GSTM1 non- (268 bp, 219 bp). Lane 5: GSTT1 , GSTM1 (268 bp). Lane 6: GSTP1 Ile/Ile (329 bp, 104 bp). Lane 7: GSTP1 Val/Val (222 bp, 107 bp, 104 bp). Lane 8: GSTP1 Ile/Val (329 bp, 222 bp, 107 bp, 104 bp).
Mentions: Genomic DNA was extracted from the blood samples obtained using EasyPure Blood Genomic DNA Kit (TransGen Biotech, Beijing, China). The GSTT1 and GSTM1 polymorphisms were genotyped by using multiplex polymerase chain reaction (PCR) technique with the beta-globin gene served as the internal control. The primers used for GSTT1 genotyping were 5'-TTCCTTACTGGTCCTCACATCTC-3' and 5'-TCACCGGATCATGGCCAGCA-3', which produced a fragment of 459 bp. On the other hand, the primers used for GSTM1 genotyping were 5'-GAACTCCCTGAAAAGCTAAAGC-3' and 5'-GTTGGGCTCAAATATACGGTGG-3', which produced a fragment of 219 bp. The 268 bp beta-globin gene was amplified by using 5'-CAACTTCATCCACGTTCACC-3' and 5'-GAAGAGCCAAGGACAGTTAC-3' primers. The multiplex PCR was performed under the following conditions: 5 min of initial denaturation at 94℃, followed by 35 cycles of 1 min at 94℃, 30 sec at 56℃, 45 sec at 72℃, and a final extension for 5 min at 72℃. The PCR products were separated on 3% agarose gels for visualization of the bands for inferring of the genotypes (Fig. 1).

Bottom Line: Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens.Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods.In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong, China.

ABSTRACT
Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P heterozygous=0.790 or P variant=0.261). Furthermore, individuals who simultaneously carried the genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.

Show MeSH
Related in: MedlinePlus