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>

Application of flexible matching strategy to detect gene-environment interactions for increasing the study power / 中华流行病学杂志

Flexible matching has recently been proposed as a method of improving interactions efficiency. In this study, the concept of flexible matching has been introduced, and the applicability of this strategy has also been described based on the power calculation of interaction between HER-2 polymorphism and smoking with breast cancer. A large-sample approximation method is used to estimate the power and efficiency of gene-environment interactions. In the basic scenario, power of interaction between HER-2 polymorphism and smoking of unmatched case-control study appears to be 30% while in the frequency matching case-control study it is 56%. However, when increasing the smoking prevalence in controls, greater power can be obtained (power=74%). Conclusions: Flexible matching strategies can increase the power and efficiency of case-control studies to detect and estimate the gene-environment interactions when compared with traditional frequency matching and it is especially useful under those scenarios when low environmental exposure of population, adverse gene-environment interactions or less paired controls are seen. Optimal matching design should be made available by weighing the benefits and loss due to flexible matching.

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>

Study on the application of classification tree model in screening the risk factors of malignant tumor / 中华流行病学杂志

<p><b>OBJECTIVE</b>To introduce the partitioning algorithm of classification tree model, and to explore the value of this data mining technique applied in data analysis of multifactorial diseases as malignant tumors.</p><p><b>METHODS</b>Data was analyzed from a survey that conducted on 84 breast cancer patients and 273 cancer-free controls selected randomly in Jiashan county. The classification tree model was constructed using Exhaustive CHAID method and evaluated by the Risk statistics and the area under the ROC curve.</p><p><b>RESULTS</b>9 out of 105 effect risks factors were selected, in which career was the most important factor indicating that workers, teachers and retirees suffered much more risks than others. Nevertheless, the number of pregnancies, breast examination, reasons for menopause, age at menarche, intake of shrimp, crab, kipper, kelp and laver etc were also risk factors on breast cancer. However, physical exercise played different roles on different people. The Risk statistics of model was 0.174, and the area under the ROC curve was 0.872 which was significantly different from 0.5, suggesting that the classification tree model fit the actuality very well.</p><p><b>CONCLUSION</b>The classification tree model could screen out the major affecting factors quickly and effectively and could also identify the cutting-points for continuous and ordinal variables, as well as revealing the complex interaction among the factors at many levels. This model might become a powerful tool to explore the complexities of the risks on diseases.</p>