Association between genetic polymorphisms in folate metabolic enzyme genes and colorectal cancer: a nested case-control study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the interrelationship of genetic polymorphisms in folate metabolic enzymes (MTHFRC677T, MTHFRA1298C, MTRA2756G and MTRRA66G) and their combinative effects with colorectal cancer (CRC).</p><p><b>METHODS</b>A nested case-control study was designed and carried out. 140 CRC patients and 343 control subjects were included in this study. Polymorphisms of folate metabolic enzyme genes were genotyped by PCR-restriction fragment length polymorphism method. Risk of CRC was estimated by unconditional logistic model, and P value for interaction was calculated by likelihood test.</p><p><b>RESULTS</b>The allele of MTR2756G showed a positive association with CRC (OR = 2.04, 95% CI = 1.22 - 3.40). Those with MTHFR1298AA and MTR 2756AG/GG genotypes had an elevated risk with CRC (OR = 2.57, 95% CI, 1.42 -4.65), and their combinative effect showed a significant association with CRC (P = 0.04).</p><p><b>CONCLUSION</b>MTR2756G allele may be a risk factor of CRC, and interaction may exsit between polymorphisms of MTHFRA1298C and MTRA2756G. Further studies with larger sample and in different ethnic groups are needed.</p>

Association between genetic polymorphisms of metabolic enzymes and susceptibility of colorectal cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association between CYP1A1, GSTM1, T1, UGT1A7 polymorphisms and colorectal cancer risk.</p><p><b>METHODS</b>A case-control study of 140 patients with cancers and 343 health controls was conducted to investigate the role of CYP1A1, GSTM1, T1, UGT1A7 polymorphisms in colorectal cancer. Gene-gene interactions among CYP1A1, GSTM1, T1, UGT1A7 polymorphisms were detected by case-control study and case-only study. Genotypes of four genes polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and unconditional logistic regression was adopted to analyze the data.</p><p><b>RESULTS</b>The CC, TC and CC genotypes of CYP1A1 T6235C significantly decreased the colorectal cancer risk as compared to TT genotype (OR = 0.493, 95% CI: 0.254-0.956, OR = 0.638, 95% CI: 0.427-0.952). GSTM1 and GSTT1 null genotype had no significant association with the increased risk of colorectal cancer while the mutant variants of UGT1A7 might increase the risk of colorectal cancer significantly (OR = 2.501, 95% CI: 1.456-4.296). The CORvalue for the gene-gene interactions between CYP1A1 variant and the null genotype of GSTT1, GSTM1-deleted and GSTT1-deleted genotype in the case-only design were 2.617 (95% CI: 1.015-6.752) and 3.935 (95% CI: 1.323-11.706), respectively. There was no significant interaction between CYP1A1 and GSTM1, CYP1A1 and UGT1A7.</p><p><b>CONCLUSION</b>This study suggests that CYP1A1 and UGT1A7 variants might be associated with colorectal cancer. CYP1A1 and GSTM1 might interact on GSTT1 to influence the risk of colorectal cancer.</p>

A case-control study on the association between genetic polymorphisms of metabolic enzymes and the risk of colorectal cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the association between metabolic enzymes polymorphisms and the risk of colorectal cancer(CRC).</p><p><b>METHODS</b>Methods of detection used were based on polymerase chain reaction(PCR) including PCR-restriction fragment length polymorphism (PCR-RFLP), allele specific-PCR (AS-PCR) and multiple-PCR to identify the polymorphisms of CYP1A1 6235T/C, CYP1A2 734C/A, CYP2E1 -1259G/C, CYP2E1 -1019C/T, GSTM1 and T1 null type, NAT1 and NAT2 alleles among 140 cases and 343 cancer-free controls.</p><p><b>RESULTS</b>The allele frequencies of CYP1A1 6235C, CYP1A2 734A, CYP2E1 -1259C, CYP2E1 -1019T, GSTM1 and T1 null type, NAT1* 10 and NAT2 Mx (x = 1,2,3) alleles were 31.65%, 63.77%, 23.02%, 32.61%, 57.25%, 17.39%, 26.45% and 39.21% in the case group and 39.85%, 66.62%, 20.27%, 28.61%, 55.46%, 20.35%, 25.22% and 39.36% in control group, respectively. The frequencies were in Hardy-Weinberg equilibrium. Data on single genetic polymorphism and stratification analysis of multi-genetic polymorphisms indicated that CYP1A1 6235CC homozygote was associated with the significant reduction of CRC risk (OR = 0.79, 95% CI: 0.63-0.99) and in individuals with CYP1A2 734A allele. CYP1A1 62345C allele had the same effect (OR = 0.53, 95% CI: 0.34-0.83). However, individuals with GSTT1 null genotype, GSTM1 null genotype could significantly increase the risk (OR = 4.41, 95% CI: 1.21-16.10).</p><p><b>CONCLUSION</b>CYP1A1 6235C allele might play an important role in fighting against colorectal carcinogenesis. However, GSTM1 and T1 null genotype might serve as risk factors genetically. Larger scale population-based studies were needed to confirm the current findings.</p>

Alcohol drinking and colorectal cancer: a population-based prospective cohort study / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To understand the incidence of colorectal cancer in population drinking or not and to validate the relationship between drinking and colorectal cancer.</p><p><b>METHODS</b>The data obtained from a questionnaire used in a population-based prospective screenings study in ten countries of Jiashan County was examined. A total of 64,102 men and women aged 30 y and older without history of cancer at baseline and a subcohort of 29,044 of them drinking past and current was conducted. Cox regression model was applied to estimate relative risk (RR).</p><p><b>RESULTS</b>After 10 years follow-up,107 colon cancer and 135 rectal cancer cases were identified. Among drinkers and abstainers, the incidence density of colorectal cancer was 36.18 per 100 thousand and 37.26 per 100 thousand, respectively and there wasn't statistical significance(Z=0.52, P>0.05); The crude RR (95%CI) for drinker compared with never drinkers was 0.97(0.75 approximately 1.25), and the multivariable-adjusted RR (95%CI) was 1.13(0.87 approximately 1.48). The research power of this study was 96.99%.</p><p><b>CONCLUSION</b>Alcohol drinking isn't one of the risk factors of colorectal cancer among Jiashan County population.</p>

Associations between genetic polymorphisms of glutathione S-transferase M1 and T1, smoking and susceptibility to colorectal cancer: a case-control study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the associations between genetic polymorphisms of glutathione S-transferase M1 and T1 (GSTM1 and GSTT1), smoking and susceptibility to colorectal cancer.</p><p><b>METHODS</b>A 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).</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>This 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.</p>

Genetic polymorphism in cytochrome P450 2E1, salted food and colorectal cancer susceptibility: a case-control study / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate PstI allelic variants of cytochrome P450 2E1 (CYP2E1), the interaction effect on salted food and their role in risk for colorectal cancer.</p><p><b>METHODS</b>The genotypes of CYP2E1 PstI restriction fragment length polymorphism were analyzed in 126 colorectal cancer cases and 343 normal controls. The unconditional logistic regression was applied to estimate the OR and its 95% CI.</p><p><b>RESULTS</b>The CYP2E1 C1/C1, C1/C2 and C2/C2 genotypes were found respectively in 61.8%, 35.8% and 2.4% of normal control, similar to rectal cancer cases. The percentage of PstI variant genotype (54.9%: 52.9% C1/C2 and 2.0% C2/C2) in colon cancer cases was significantly higher than that in controls (adjusted OR1.979, 95% CI 1.090 approximately 3.595). Stratified analysis suggested an interaction between CYP2E1 C2 allele and salted food. The odds ratio (OR) for the CYP2E1 variant genotype, salted food eaten weekly or biweekly and eaten every day or every other day were 1.935, 2.122 and 2.315, respectively, while those of salted food combined with variant genotype eaten weekly or biweekly and eaten every day or every other day were 2.272 and 3.127. The role in risk for rectal cancer was different from that for colon cancer. Whatever the CYP2E1 genotype is, the risk for rectal cancer came to marked when salted food was consumed weekly or biweekly (OR = 2.646 and 2.297, respectively). However, none but the combined effect of variant genotype and salted food eaten every day or every other day had the notably risk for colon cancer and the odds ratio suddenly increased to 4.262 (95% CI 1.395 approximately 13.017), 1.69-fold higher than that of wild genotype (P = 0.072).</p><p><b>CONCLUSION</b>The CYP2E1 C2 allele is a susceptibility factor for colorectal cancer, especially for colon cancer, and there is an apparent gene-environment interaction between the susceptible genotype and salted food.</p>

A case-control study on the polymorphisms of methylenetetrahydrofolate reductases, drinking interaction and susceptibility in colorectal cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between methylenetetrahydrofolate reductases (MTHFR) polymorphisms and colorectal cancer susceptibility.</p><p><b>METHODS</b>A case-control study of 126 patients and 343 healthy controls was conducted to investigate the roles of MTHFR C677T and A1298C polymorphisms in colorectal cancer development. Genotypes of C677T and A1298C polymorphisms were analyzed by polymerase chain resction-restriction fragment length polymorphism (PCR-RFLP) methods.</p><p><b>RESULTS</b>The frequencies of MTHFR 677T and 1298C allele were 39.7% and 17.1%, respectively. After adjustment for age and sex, the MTHFR 1298C alleles seemed to have reduced association on the risk of colorectal cancer comparing to wild types. Among those with 677T and 1298A alleles, a decreased risk of colorectal cancer was observed: a 4-fold decrease in colorectal cancer risk (OR = 0.552, 95% CI: 0.265 - 1.150) in those with 677T and 1298C alleles. Men who were ex-drinkers and with MTHFR 1298C allele had a 2-fold increase in risk of colorectal cancer (OR = 3.307, 95% CI: 0.521 - 17.698) while no increased risk was seen among those current-drinkers.</p><p><b>CONCLUSIONS</b>This study suggested that certain MTHFR C677T and A1298C might be associated with the risk of colorectal cancer development. The interaction between MTHFR 1298AC polymorphisms and ex-drinking might also serve as a risk factor of colorectal cancer.</p>