Dataset Information

Variants in the GH-IGF axis confer susceptibility to lung cancer.

ABSTRACT: We conducted a large-scale genome-wide association study in UK Caucasians to identify susceptibility alleles for lung cancer, analyzing 1529 cases and 2707 controls. To increase the likelihood of identifying disease-causing alleles, we genotyped 1476 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 871 candidate cancer genes, biasing SNP selection toward those predicted to be deleterious. Statistically significant associations were identified for 64 nsSNPs, generating a genome-wide significance level of P=0.002. Eleven of the 64 SNPs mapped to genes encoding pivotal components of the growth hormone/insulin-like growth factor (GH-IGF) pathway, including CAMKK1 E375G (OR=1.37, P=5.4x10(-5)), AKAP9 M463I (OR=1.32, P=1.0x10(-4)) and GHR P495T (OR=12.98, P=0.0019). Significant associations were also detected for SNPs within genes in the DNA damage-response pathway, including BRCA2 K3326X (OR=1.72, P=0.0075) and XRCC4 I137T (OR=1.31, P=0.0205). Our study provides evidence that inherited predisposition to lung cancer is in part mediated through low-penetrance alleles and specifically identifies variants in GH-IGF and DNA damage-response pathways with risk of lung cancer.

SUBMITTER: Rudd MF

PROVIDER: S-EPMC1473180 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Variants in the GH-IGF axis confer susceptibility to lung cancer.

Rudd Matthew F MF Webb Emily L EL Matakidou Athena A Sellick Gabrielle S GS Williams Richard D RD Bridle Helen H Eisen Tim T Houlston Richard S RS

Genome research 20060601 6

We conducted a large-scale genome-wide association study in UK Caucasians to identify susceptibility alleles for lung cancer, analyzing 1529 cases and 2707 controls. To increase the likelihood of identifying disease-causing alleles, we genotyped 1476 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 871 candidate cancer genes, biasing SNP selection toward those predicted to be deleterious. Statistically significant associations were identified for 64 nsSNPs, generating a genome-wide sign ...[more]

PMID: 16741161

Similar Datasets

Project description:Background Complement system plays an important role in innate immunity which involved in the changes tumor immune microenvironment by mediating the inflammatory response. This study aims to explore the relationship between complement component 7 (C7) polymorphisms and the risk of gastric cancer (GC). Materials and Methods All selected SNPs of C7 were genotyped in 471 patients and 471 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional Logistic regression to analyze the relationship between each genotype and the genetic susceptibility to gastric cancer. The level of C7 expression in GC was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and detected by Enzyme Linked Immunosorbent Assay. Kaplan–Meier plotter were used to reveal C7 of prognostic value in GC. We examined SNPs associated with the expression of C7 using the GTEx database. The effect of C7 polymorphisms on the regulatory activity of C7 was detected by luciferase reporter assay. Results Unconditional logistic regression showed that individuals with C7rs1376178 AA or CA genotype had a higher risk of GC with OR (95% CI) of 2.09 (1.43–3.03) and 1.88 (1.35–2.63), respectively. For C7rs1061429 C > A polymorphism, AA genotype was associated with the elevated risk for developing gastric cancer (OR = 2.16, 95% CI [1.37–3.38]). In stratified analysis, C7rs1376178 AA genotype increased the risk of GC among males (OR = 2.88, 95% CI [1.81–4.58]), but not among females (OR = 1.06, 95% CI [0.55–2.06]). Individuals carrying rs1061429 AA significantly increased the risk of gastric cancer among youngers (OR = 2.84, 95% CI [1.39–5.80]) and non-smokers (OR = 2.79, 95% CI [1.63–4.77]). C7 was overexpressed in gastric cancer tissues and serum of cancer patients and was significantly associated with the prognosis. C7rs1061429 C > A variant contributed to reduced protein level of C7 (P = 0.029), but rs1376178 didn’t. Luciferase reporter assay showed that rs1376178C-containing plasmid exhibited 2.86-fold higher luciferase activity than rs1376178 A-containing plasmid (P < 0.001). We also found that rs1061429A allele contributed 1.34-fold increased luciferase activity than rs1061429C allele when co-transfected with miR-591 (P = 0.0012). Conclusions These findings highlight the role of C7 in the development of gastric cancer.

Dataset Information

Variants in the GH-IGF axis confer susceptibility to lung cancer.

Publications

Variants in the GH-IGF axis confer susceptibility to lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets