1.Associations between genetic polymorphisms of glutathione S-transferase M1 and T1, smoking and susceptibility to colorectal cancer: a case-control study.
Kun CHEN ; Qin-ting JIANG ; Xin-yuan MA ; Kai-yan YAO ; Shu-guang LENG ; Wei-ping YU ; Hai-guang ZHOU
Chinese Journal of Oncology 2004;26(11):645-648
OBJECTIVETo evaluate the associations between genetic polymorphisms of glutathione S-transferase M1 and T1 (GSTM1 and GSTT1), smoking and susceptibility to colorectal cancer.
METHODSA case-control study of 126 patients and 343 healthy controls was conducted to investigate the role of GSTM1 and GSTT1 polymorphisms in colorectal cancer. Genotypes of GSTM1 and GSTT1 polymorphisms were analyzed by multiplex allele-specific polymerase chain reaction (PCR).
RESULTSThe frequencies of GSTM1 null and GSTT1 null genotypes were 55.5% and 20.4%, respectively. After adjustment for age and sex, among those with GSTT1 null genotype, the GSTM1 null genotype had a significant increased risk of rectal cancers compared to GSTM1 non-null genotype (OR=9.74, 95% CI, 1.13 - 83.85). A 2.22-fold risk of colon cancers was associated with GSTM1 null genotype compared to GSTM1 non-null genotype among current smokers (P >0.05). Individuals with GSTT1 null genotype and currently smoking had a significant risk of colon cancers (OR = 4.55, 95% CI, 1.14 - 18.17), and rectal cancers (OR = 4.60, 95% CI, 1.11 - 19.11).
CONCLUSIONThis study suggests that certain null GSTM1 and GSTT1 genotypes may be associated with an elevated risk of colorectal cancer which may be modified by interaction of the two genetic polymorphisms and cigarette smoking.
Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Colonic Neoplasms ; enzymology ; genetics ; Female ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Rectal Neoplasms ; enzymology ; genetics ; Risk Factors ; Smoking ; adverse effects
2.Change of telomerase activity in rectal cancer with chemoradiation therapy.
Hyeong Rok KIM ; Young Jin KIM ; Hyun Jong KIM ; Shin Kon KIM ; Ji Hee LEE
Journal of Korean Medical Science 2000;15(2):167-172
Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant cells and is inactive in most normal somatic cells, with the exception of proliferative stem cells, germ cells and activated lymphocytes. Measuring telomerase activity clinically may provide useful diagnostic and prognostic information of cancer. The purpose of this study was to investigate the change in telomerase activity following chemoradiation in rectal cancer, which almost always produces positive enzymatic activity. A total of 24 tumor tissue samples were used in this study, consisting of 12 paired specimens before and 4 week after chemoradiation. Telomerase activity was determined by PCR-based telomeric repeat amplification protocol (TRAP) assay. The telomerase activity was positive in 10 out of 12 patients (83%) in pre-irradiated and post-irradiated states. The levels of telomerase activity was decreased in 8 out of 10 patients after chemoradiation (80%) and two cases showed no change in enzymatic activity. One case showed no activity in either sample. The other case showed no enzymatic activity in the pre-irradiated sample, but showed weak activity in the post-irradiated sample. These data indicate that telomerase activity in rectal cancer is reduced after neoadjuvant chemoradiation therapy, possibly suggesting a mechanism of downstaging following chemoradiation therapy in cancer.
Adult
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Aged
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Antimetabolites, Antineoplastic/administration & dosage
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Antineoplastic Agents/administration & dosage
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Cisplatin/administration & dosage
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Combined Modality Therapy
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Enzyme Activation/radiation effects
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Enzyme Activation/drug effects
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Female
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Fluorouracil/administration & dosage
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Gene Amplification
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Human
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Male
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Middle Age
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Rectal Neoplasms/radiotherapy*
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Rectal Neoplasms/enzymology*
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Rectal Neoplasms/drug therapy
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Telomerase/metabolism*
3.High expression of proteasome subunit PSMA7 in colorectal cancer is significantly correlated with liver metastasis.
Xiao-Tong HU ; Wei CHEN ; Da WANG ; Qing-Lan SHI ; Fu-Biao ZHANG ; Yong-Qiang LIAO ; Mei JIN ; Chao HE
Chinese Journal of Oncology 2008;30(7):515-518
OBJECTIVETo investigate the correlation between the proteasome subunit PSMA7 expression in colorectal cancer and its role in liver metastasis.
METHODSTo identify the PSMA7 protein expression in 62 primary site colorectal cancers, 34 lymph node metastatic sites and 13 liver metastatic sites by immunohistochemistry and clarify the correlation of its expression with the clinicopathological parameters.
RESULTSHigh expression of PSMA7 was detected in 38.7% (24/62) of primary site colorectal cancer, 52.9% (18/34) of lymph node metastatic sites and 100% (13/13) liver metastatic sites but not in the normal colorectal tissue. High expression of PSMA7 was significantly correlated with liver metastasis (P = 0.028). The survival rate was significantly lower in patients with high expression of PSMA7 than in those with low expression of PSMA7 (P = 0.0008). As well, in multivariate analysis, PSMA7 expression demonstrated to be an independent prognostic factor (P = 0.004, relative risk 5.057; 95% confidence interval, 1.682-15.201).
CONCLUSIONPSMA7 may play an important role in the colorectal cancer progression. Evaluation of PSMA7 expression in primary colorectal cancer at the time of surgery might be a valuable test in defining patients with a high risk of developing liver metastasis.
Adult ; Aged ; Colonic Neoplasms ; enzymology ; pathology ; surgery ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; enzymology ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Proteasome Endopeptidase Complex ; metabolism ; Rectal Neoplasms ; enzymology ; pathology ; surgery ; Survival Rate ; Young Adult
4.Association between genetic polymorphism in STK15 and risk of colorectal cancer in a Chinese population.
Wen-jie ZHANG ; Xiao-ping MIAO ; Tong SUN ; Xue-mei ZHANG ; Shi-ning QU ; Wen TAN ; Ping XIONG ; Rong ZHENG ; Dong-xin LIN
Chinese Journal of Oncology 2006;28(1):43-46
OBJECTIVEThis case-control study was designed to detect the association between STK15 Phe31Ile polymorphism and colorectal cancer.
METHODSGenotypes were determined in 283 patients with colorectal cancer and 283 controls. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression model.
RESULTSThe frequency of the STK15 Ile/Ile genotype was significantly higher in cancer cases than in controls (50.2% vs. 36.8%; P = 0.02). Subjects with the Ile/Ile genotype had an increased risk for the occurrence of colorectal cancer compared with those with the STK15 Phe/Phe genotype (adjusted OR, 1.92; 95% CI, 1.13 - 3.27). No significant association was observed between this STK15 polymorphism and risk of metastasis of the cancer.
CONCLUSIONThese findings suggest that STK15 Phe/Ile polymorphism may be a genetic susceptibility factor for colorectal cancer among Chinese.
Adult ; Aged ; Amino Acid Substitution ; Aurora Kinase A ; Aurora Kinases ; Case-Control Studies ; Colonic Neoplasms ; enzymology ; genetics ; pathology ; Confidence Intervals ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Odds Ratio ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Rectal Neoplasms ; enzymology ; genetics ; pathology ; Risk Factors
5.A case-control study on the association between the genetic polymorphism of sulfotransferase 1A1, diet and susceptibility of colorectal cancer.
Kun CHEN ; Chun-hong FAN ; Ming-juan JIN ; Liang SONG ; Hong XU ; Han-qing HE ; Feng TONG
Chinese Journal of Oncology 2006;28(9):670-673
OBJECTIVETo investigate the relationship between sulfotransferase 1Al polymorphism, diet and colorectal cancer susceptibility.
METHODSA case-control study of 140 cancers and 343 health controls was conducted to investigate the role of sulfotransferase 1A1 polymorphism and meat consumption in colorectal carcinogenesis. Genotypes of sulfotransferase 1A1 polymorphism were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
RESULTSThere was no significant difference in allele frequency of SULT1A1 between the control and cancer patient populations. After adjustment for age, sex, smoking and history of diseases, red meat and well-done meat intake showed no significant association with colorectal cancer. Consumption of red meat more than 5 kg per year combined with SULT1Al slow sulfation (Arg/His and His/His) had a statistically significant association with the risk of rectal cancer ( OR = 3.78; 95% CI: 1.08 - 13. 20) compared to that consumed red meat less than 5 kg per year with fast sulfation (Arg/Arg).
CONCLUSIONThis study suggests that SULT1A1 slow sulfation combined with higher intake of red meat may be associated with an elevated risk of rectal cancer.
Aged ; Alleles ; Animals ; Arylsulfotransferase ; genetics ; Case-Control Studies ; Cattle ; Colonic Neoplasms ; enzymology ; etiology ; genetics ; Diet ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Meat ; adverse effects ; Middle Aged ; Polymorphism, Genetic ; Rectal Neoplasms ; enzymology ; etiology ; genetics ; Risk Factors ; Smoking ; adverse effects ; Swine