Large-scale evaluation of genetic variants in candidate genes for colorectal cancer risk in the Nurses' Health Study and the Health Professionals' Follow-up Study
ABSTRACT Advances in genomics offer new strategies for assessing the association of common genetic variations at multiple loci and risk of many diseases, including colorectal cancer. Low-penetrance alleles of genes in many biological pathways, such as DNA repair, metabolism, inflammation, cell cycle, apoptosis, and Wnt signaling, may influence the risk of nonfamilial colorectal cancer. To identify susceptibility genes for colorectal cancer, we designed a large-scale case-control association study nested within the Nurses' Health Study (190 cases and 190 controls) and the Health Professionals' Follow-up Study (168 cases and 168 controls). We used a custom GoldenGate (Illumina) oligonucleotide pool assay including 1,536 single nucleotide polymorphisms (SNP) selected in candidate genes from cancer-related pathways, which have been sequenced and genotyped in the SNP500Cancer project; 1,412 of the 1,536 (92%) of the SNPs were genotyped successfully within 388 genes. SNPs in high linkage disequilibrium (r(2) >/= 0.90) with another assayed SNP were excluded from further analyses. As expected by chance (and not significant compared with a corrected Bonferroni P = 0.00004), in the additive model, 11 of 1,253 (0.9%) SNPs had a P(trend) < 0.01 and 38 of 1,253 (3.0%) SNPs had a P(trend) >/= 0.01 and P(trend) < 0.05. Of note, the MGMT Lys(178)Arg (rs2308237) SNP, in linkage disequilibrium with the previously reported MGMT Ile(143)Val SNP, had an inverse association with colorectal cancer risk (MGMT Lys(178)Arg: odds ratio, 0.52; 95% confidence interval, 0.35-0.78; unadjusted P(trend) = 0.0003 for the additive model; gene-based test global P = 0.00003). The SNP500Cancer database and the Illumina GoldenGate Assay allowed us to test a larger number of SNPs than previously possible. We identified several SNPs worthy of investigation in larger studies.
SourceAvailable from: Anna IatsyshynaBiopolymers and Cell 09/2013; 29(5):367-374. DOI:10.7124/bc.00082B
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ABSTRACT: Many studies have examined the association between the MGMT Leu84Phe polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case-control studies published up to Nov. 2013. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 7 studies, comprising 3,094 lung cancer cases and 4,216 controls, were included. Overall, for (Phe/Phe+Phe/Leu) versus Leu/Leu, the pooled OR for all studies was 1.08 (95 % CI = 0.97-1.21 P = 0.518 for heterogeneity); for Phe/Phe versus Leu/Leu and Phe versus Leu, the pooled OR was 1.10 (95 % CI = 0.99-1.21 P = 0.445 for heterogeneity) and 1.46 (95 % CI = 1.05-2.02 P = 0.352 for heterogeneity), respectively. In the stratified analysis by ethnicity, significantly risks were found among Caucasians not in Asians. This meta-analysis suggests that the MGMT Leu84Phe polymorphisms are associated with lung cancer risk among Caucasians not in Asians.Tumor Biology 01/2014; DOI:10.1007/s13277-013-1576-3 · 2.84 Impact Factor
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ABSTRACT: Background: Colorectal cancer is the third most common cancer in both men and women in the world and the second leading cause of cancer-related deaths. The incidence of colorectal cancer has increased in Iran in the past three decades and is now considered as a serious problem for our society. This cancer has two types hereditary and non-hereditary, 80% of cases being the latter. Considering that the relationship between SNPs with diseases is a concern, many researchers believed that they offer valuable markers for identifying genes responsible for susceptibility to common diseases. In some cases, they are direct causes of human disease. One SNP can increase risk of cancer, but when considering the rate of overlap and frequency of DNA repair pathways, it might be expected that SNP alone cannot affect the final result of cancer, although several SNPs together can exert a significant influence. Therefore identification of these SNPs is very important. The most important loci which include mutations are: MLH1, MSH2, PMS2, APC, MUTYH, SMAD7, STK11, XRCC3, DNMT1, MTHFR, Exo1, XRCC1 and VDR. Presence of SNPs in these genes decreases or increases risk of colorectal cancer. Materials and Methods: In this article we reviewed the Genes and SNPs associated with non-hereditary and hereditary of colorectal cancer that recently were reported from candidate gene y, meta-analysis and GWAS studies. Results: As with other cancers, colorectal cancer is associated with SNPs in gene loci. Generally, by exploring SNPs, it is feasible to predict the risk of developing colorectal cancer and thus establishing proper preventive measures. Conclusions: SNPs of genes associated with colorectal cancer can be used as a marker SNP panel as a potential tool for improving cancer diagnosis and treatment planning.Asian Pacific journal of cancer prevention: APJCP 10/2013; 14(10):5609-14. DOI:10.7314/APJCP.2013.14.10.5609 · 1.50 Impact Factor