An analysis of growth, differentiation and apoptosis genes with risk of renal cancer

• Published in: PloS one 2009-03, Vol.4 (3), p.e4895
• Main Authors: Dong, Linda M, Brennan, Paul, Karami, Sara, Hung, Rayjean J, Menashe, Idan, Berndt, Sonja I, Yeager, Meredith, Chanock, Stephen, Zaridze, David, Matveev, Vsevolod, Janout, Vladimir, Kollarova, Hellena, Bencko, Vladimir, Schwartz, Kendra, Davis, Faith, Navratilova, Marie, Szeszenia-Dabrowska, Neonila, Mates, Dana, Colt, Joanne S, Holcatova, Ivana, Boffetta, Paolo, Rothman, Nathaniel, Chow, Wong-Ho, Rosenberg, Philip S, Moore, Lee E
• Format: Article
• Language: English
• Subjects: Adult; Apoptosis; Apoptosis - genetics; Cancer; Cancer genetics; Cancer research; Carcinogenesis; Carcinogens; Case-Control Studies; Caspase; Caspase-1; Cell differentiation; Cell Differentiation - genetics; Cell Proliferation; Deoxyribonucleic acid; Differentiation (biology); DNA; Epidemiology; Epidermal growth factor; Epidermal growth factor receptors; Epidermal growth factors; Female; Genes; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genetics and Genomics/Genetics of Disease; Genotype; Growth; Health risk assessment; Health risks; Humans; Insulin; Insulin-like growth factor-binding protein 3; Kidney cancer; Kidney Neoplasms - epidemiology; Kidney Neoplasms - genetics; Kidneys; Male; Middle Aged; Mutation; Oncology/Renal Cancer; Polymorphism, Single Nucleotide; Protein binding; Public Health and Epidemiology/Epidemiology; Regression analysis; Risk; Risk Factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004895

We conducted a case-control study of renal cancer (987 cases and 1298 controls) in Central and Eastern Europe and analyzed genomic DNA for 319 tagging single-nucleotide polymorphisms (SNPs) in 21 genes involved in cellular growth, differentiation and apoptosis using an Illumina Oligo Pool All (OPA). A haplotype-based method (sliding window analysis of consecutive SNPs) was used to identify chromosome regions of interest that remained significant at a false discovery rate of 10%. Subsequently, risk estimates were generated for regions with a high level of signal and individual SNPs by unconditional logistic regression adjusting for age, gender and study center. Three regions containing genes associated with renal cancer were identified: caspase 1/5/4/12(CASP 1/5/4/12), epidermal growth factor receptor (EGFR), and insulin-like growth factor binding protein-3 (IGFBP3). We observed that individuals with CASP1/5/4/12 haplotype (spanning area upstream of CASP1 through exon 2 of CASP5) GGGCTCAGT were at higher risk of renal cancer compared to individuals with the most common haplotype (OR:1.40, 95% CI:1.10-1.78, p-value = 0.007). Analysis of EGFR revealed three strong signals within intron 1, particularly a region centered around rs759158 with a global p = 0.006 (GGG: OR:1.26, 95% CI:1.04-1.53 and ATG: OR:1.55, 95% CI:1.14-2.11). A region in IGFBP3 was also associated with increased risk (global p = 0.04). In addition, the number of statistically significant (p-value