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1.  An analysis of single nucleotide polymorphisms of 125 DNA repair genes in the Texas genome-wide association study of lung cancer with a replication for the XRCC4 SNPs 
DNA repair  2011;10(4):398-407.
DNA repair genes are important for maintaining genomic stability and limiting carcinogenesis. We analyzed all single nucleotide polymorphisms (SNPs) of 125 DNA repair genes covered by the Illumina HumanHap300 (v1.1) BeadChips in a previously conducted genome-wide association study (GWAS) of 1,154 lung cancer cases and 1,137 controls and replicated the top-hits of XRCC4 SNPs in an independent set of 597 cases and 611 controls in Texas populations. We found that six of 20 XRCC4 SNPs were associated with a decreased risk of lung cancer with a P value of 0.01 or lower in the discovery dataset, of which the most significant SNP was rs10040363 (P for allelic test = 4.89 ×10−4). Moreover, the data in this region allowed us to impute a potentially functional SNP rs2075685 (imputed P for allelic test = 1.3 ×10−3). A luciferase reporter assay demonstrated that the rs2075685G>T change in the XRCC4 promoter increased expression of the gene. In the replication study of rs10040363, rs1478486, rs9293329, and rs2075685, however, only rs10040363 achieved a borderline association with a decreased risk of lung cancer in a dominant model (adjusted OR = 0.80, 95% CI = 0.62–1.03, P = 0.079). In the final combined analysis of both the Texas GWAS discovery and replication datasets, the strength of the association was increased for rs10040363 (adjusted OR = 0.77, 95% CI = 0.66–0.89, Pdominant = 5×10−4 and P for trend = 5×10−4) and rs1478486 (adjusted OR = 0.82, 95% CI = 0.71 −0.94, Pdominant = 6×10−3 and P for trend = 3.5×10−3). Finally, we conducted a meta-analysis of these XRCC4 SNPs with available data from published GWA studies of lung cancer with a total of 12,312 cases and 47,921 controls, in which none of these XRCC4 SNPs was associated with lung cancer risk. It appeared that rs2075685, although associated with increased expression of a reporter gene and lung cancer risk in the Texas populations, did not have an effect on lung cancer risk in other populations. This study underscores the importance of replication using published data in larger populations.
PMCID: PMC3062723  PMID: 21296624
XRCC4; variant; Genetic susceptibility; genome-wide association study; replication study
2.  Common 5p15.33 and 6p21.33 variants influence lung cancer risk 
Nature genetics  2008;40(12):1407-1409.
We conducted a genome-wide association (GWA) study of lung cancer comparing 511,919 SNP genotypes in 1,952 cases and 1,438 controls. The most significant association was attained at 15q25.1 (rs8042374; P = 7.75 × 10−12), confirming recent observations. Pooling data with two other GWA studies (5,095 cases, 5,200 controls) and with replication in an additional 2,484 cases and 3,036 controls, we identified two newly associated risk loci mapping to 6p21.33 (rs3117582, BAT3-MSH5; Pcombined = 4.97 × 10−10) and 5p15.33 (rs401681, CLPTM1L; Pcombined = 7.90 × 10−9).
PMCID: PMC2695928  PMID: 18978787
3.  Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1 
Nature genetics  2008;40(5):616-622.
To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 × 10−17) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk.
PMCID: PMC2713680  PMID: 18385676

Results 1-3 (3)