Association between H-ras and L-myc gene polymorphisms and susceptibility to colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the association between the polymorphisms of oncogenes H-ras and L-myc and colorectal cancer risk, and the interaction of those genes.</p><p><b>METHODS</b>The genotypes of H-ras and L-myc genes were determined by polymerase chain reaction-based restriction fragment length polymorphism analysis. Stratified analysis and logistic model were used to detect the gene-gene interaction. The gene-gene interaction was validated by multifactor dimensionality reduction (MDR) analysis.</p><p><b>RESULTS</b>The single SNP model showed that the polymorphisms of H-ras and L-myc genes were not significantly related with colorectal cancer risk (P > 0.05). Stratified analysis revealed that among the L-myc LS + SS genotype carriers, those with H-ras TC + CC genotype showed significantly increased risk of rectal cancer than those with TT genotype (OR = 1.81, P = 0.005). The positive interaction between L-myc and H-ras was detected by logistic regression model. The OR of the interaction effect was 2.74 (P = 0.024). This result was confirmed in the MDR model, with 54.83% testing balanced accuracy and 10/10 cross-validation consistency, and the model was still significant after the 1000 times permutation test (P = 0.001).</p><p><b>CONCLUSION</b>Our findings suggest that the polymorphism of H-ras and L-myc genes is not related to colorectal cancer risk, but there is a synergy between H-ras and L-myc polymorphisms in the development of rectal cancer.</p>

Expression of caspase apoptosis pathway genes mRNA in colorectal cancer and polyps / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate mRNA expression of caspase apoptosis pathway genes in colorectal cancer, polyps and normal mucosa.</p><p><b>METHODS</b>Nineteen patients with colorectal cancer, 86 patients with polyps and 10 normal controls were enrolled from 2008 to 2010. Fluorescence quantitative RT-PCR was performed to detect the mRNA expression of caspase apoptosis pathway genes (caspase-2,-3,-6,-7,-8,-9 and -10) in colorectal cancer, polyps and normal mucosa.</p><p><b>RESULT</b>There were no statistically significant differences of demographic characteristics between patients with colorectal cancer, patients with polyps and normal controls. Compared with normal control group, the mRNA expression of all selected genes except for caspase-3 were lower; however, the P values did not reach statistic significance. Highly positive correlations were observed between mRNA expression of all selected genes except caspase-9.</p><p><b>CONCLUSION</b>There are no significant changes in mRNA expression levels of caspase apoptosis pathway genes from normal mucosa to polyps to cancer. The mRNA expressions of most caspase pathway genes are highly correlated with each other.</p>

Association of XPC gene polymorphisms with breast cancer risk / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To access the association of xeroderma pigmentosum group C (XPC) Lys939Gln (A/C) and Ala499Val (C/T) polymorphisms with breast cancer risk in a Chinese Han population.</p><p><b>METHODS</b>173 patients with breast cancer and 171 matched controls in terms of habitation and age (±5 years) were included in this population-based case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was employed to genotyping the Lys939Gln and Ala499Val polymorphisms. Associations of genotypes of Lys939Gln and Ala499Val with breast cancer risk were evaluated using unconditional logistic regression model. Associations between XPC haplotypes and breast cancer risk were estimated by Haplo. Stats package.</p><p><b>RESULT</b>No significant associations were observed both in individual SNPs and haplotype analyses. However, there was a significant interaction between XPC Lys939Gln polymorphism and menopausal status (P=0.032).</p><p><b>CONCLUSION</b>The XPC Lys939Gln polymorphism may modulate breast cancer susceptibility jointly with the menopausal status.</p>

Association of CASP3 polymorphisms and its haplotypes with susceptibility of breast cancer / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the association of Caspase3 (CASP3) polymorphisms with susceptibility of breast cancer in Chinese Han population.</p><p><b>METHODS</b>In this population-based case-control study, 251 cases with breast cancers and 251 matched controls in terms of habitation and age (±5 years) were recruited. Rs4647693, rs2696056, rs4647610 were selected as TagSNPs in CASP3 gene and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The haplotype distribution was estimated and compared by PHASE software.</p><p><b>RESULT</b>There was significant association between menarche age and breast cancer (P=0.007), as well as the early pregnancy age and breast cancer (P=0.002). No significant differences were detected in the distribution of CASP3 genotype and haplotype frequencies between breast cancer patients and controls. The GGA was the most common haplotype both in cases and controls.</p><p><b>CONCLUSION</b>CASP3 polymorphisms and its haplotypes were not related to the susceptibility of breast cancer.</p>

Optimization of sequential screening scheme in prevention of colorectal neoplasm / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To improve early diagnosis rate and reduce the incidence rate of colorectal cancer, through the application of optimized sequential screening scheme for colorectal neoplasm in general population.</p><p><b>METHODS</b>Quantitative risk assessment by questionnaires survey and fecal occult blood test (FOBT) were used to proceed preliminary screening among people aged 40 to 74. Electronic colonoscopy was applied to examine the whole colon and rectum among identified high-risk subjects. The detected cases received treatment for colorectal cancer, adenomatous polyps or non-adenomatous polyps. The early diagnosis rate and incidence rate of colorectal cancer were evaluated and compared with those before screening.</p><p><b>RESULT</b>With application of optimized sequential screening schemes, various types of colorectal lesions were detected in 1 117 subjects, including 69 cases of colorectal cancer, 701 cases of colorectal adenoma and 211 cases of advanced adenoma. The early diagnosis rate of colorectal cancer was increased by 58.19%, and its incidence rate also decreased significantly.</p><p><b>CONCLUSION</b>The optimized sequential screening scheme is simple, economical, efficient in colorectal cancer screening of general population.</p>

Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the distribution of HER-2 genetic polymorphism at codon 655 and its association with susceptibility of colorectal cancer in Chinese.</p><p><b>METHODS</b>A population-based case-control study was carried out. 292 patients with colorectal cancer and 842 healthy controls were interviewed. Meanwhile, the genetic polymorphism of HRE-2 was detected using polymerase chain reaction-restriction fragment length polymorphism.</p><p><b>RESULTS</b>The frequencies of Ile/Val+Val/Val genotypes and Val allele were both higher in cases (25.34% and 13.36%) than those in controls (18.41% and 9.74%) (P<0.05). Compared with Ile/Ile genotype, Ile/Val+Val/Val genotypes were significantly associated with colorectal cancer [ORadjusted=1.54, 95% CI: 1.11-2.14]. The adjusted odds ratio of interactions between this polymorphism and smoking, alcohol drinking were 1.43 (95%CI: 0.88-2.30) and 1.29 (95%CI: 0.73-2.29), respectively.</p><p><b>CONCLUSION</b>The present findings suggest that HER-2 genetic polymorphism at codon 655 may be associated with the risk of colorectal cancer in Chinese. In addition, there are no interactions between this polymorphism and smoking, alcohol drinking, respectively.</p>

Application of multifactor dimensionality reduction on the interactions between gene-gene,geneenvironment and the risk sporadic colorectal cancer in Chinese population / 中华流行病学杂志

Objective To identify the association between risk of sporadic colorectal cancer and the common single nucleotide polymorphisms (SNPs) in DNA repairs genes, gene to gene interactions among them and their gene to environment interactions with common environmental factors. Methods In this population-based case-control study, 206 primary colorectal cancer cases and 845 cancer-free healthy controls were enrolled. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, with the status of subjects case or controls unknown.Multifactor dimensionality reduction (MDR) and logistic analysis were both used for association analysis.Results As compared to the younger age group (≥42,＜61 years), the risk of colorectal cancer in older age group (≥61 years) increased significantly ( OR = 2.04,95% CI: 1.49-2.80). Similar result was observed in the family cancer history ( OR = 1.51, 95% CI : 1.05-2.17 ). However, no significant association between any single DNA repair gene SNP and colorectal cancer risk was discovered. Results from MDR analysis only showed a significant interaction among the four following factors: age, alcohol drinking, XRCC1 Arg194Trp and OGG1 Ser326Cys (the cross-validation consistency = 10/10, the average testing accuracy = 0. 616, P=0.011 ). Using a logistic regression model, the"high-risk"individuals had a significantly elevated risk of colorectal cancer compared to those "low- risk" individuals classified by the above MDR model ( OR = 2.72,95% CI : 1.66-4.47 ). Conclusion The impact of polymorphisms in DNA repair genes on the risk of sporadic colorectal cancer exhibited a low-penetrance characteristics while the intricate interactions existing among them and with environmental factors.

Association of single nucleotide polymorphisms and haplotypes in DNA repair gene XRCC1 with susceptibility of breast cancer / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To examine the contribution of the three most common single nucleotide polymorphisms (SNPs) in XRCC1 gene, C26304T, G27466A and G28152A, to susceptibility of breast cancer in Chinese Han population.</p><p><b>METHODS</b>In this population-based case control study, 84 cases with breast cancer and 252 controls, matched to the cases in terms of habitation and age (5 years), were genotyped for the XRCC1 C26304T, G27466A and G28152A polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The haplotype distribution was estimated and compared by EH linkage software 1. 2.</p><p><b>RESULT</b>The distribution of basic characteristics, such as age, alcohol drinking, the family history of malignancy in first and second relatives except cigarette smoking, were not significantly different between cases and controls. However, the percentage of ever or current smokers was significantly higher in cases (7.1%) than that in controls (2.0%). The distributions of allelotype and genotype of C26304T, G27466A and G28152A polymorphisms were also not significantly different between cases and controls. There was no significant association between the risk of breast cancer and these three SNPs of XRCC1 gene. The genetic linkage disequilibrium existed in these three polymorphic sites both in cases and controls, in which the CGG, CGA, CAG and TGG haplotypes were the most common. There was also no significant association of XRCC1 haplotype with risk of breast cancer.</p><p><b>CONCLUSION</b>XRCC1 C26304T, G27466A and G28152A SNPs may not be associated with the susceptibility of breast cancer. The CGG, CGA, CAG and TGG haplotypes might be the most common haplotypes in Chinese Han population.</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>

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>