Identification of single nucleotide polymorphisms associated with lung cancer in a genome-wide association case-control study.


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Nicosha De Souza1, Ying Chen1, Michael Marcus1, Olaide Raji1, Russell Hyde1, John K Field1
1University Of Liverpool, Liverpool, UK

Background

Genome wide association studies (GWAS) have previously demonstrated a link between chromosomal regions 15q24-25.1, 5p15.33 and 6p21 and lung cancer susceptibility (1-3). This study was carried out to identify further SNPs associated with lung cancer.

Method

Five hundred and seventy histologically or cytologically confirmed, consented cases between 20-80 years of age were recruited and genotyped using the Illumina Human Hap 300k array. 3000 control subjects were derived from the WTCCC 1958 Birth cohort. Rigorous data quality controls were applied. Association tests (using PLINK) were performed using the allelic, dominant, recessive and genotypic models and Bonferroni corrected.

Results

The three most significant SNPs were rs10838427, rs2162296 and rs1563834. rs10838427,located in the PRDM11 gene, was significant in the allelic (OR=0.51; 95%CI: 0.43-0.6; p=1.56E-17), dominant (OR=0.33; 95%CI: 0.27-0.40; p=1.86E-29) and genotypic model (ORhet =0.26; 95%CIhet: 0.21-0.33 and ORhom=0.60; 95%CIhom : 0.44-0.81; p=1.7E-31). rs2162296, located in the ZNF382, was significant in the allelic (OR=0.45; 95%CI: 0.36-0.55; p=6.30E-15), dominant (OR=0.41; 95%CI: 0.33-0.51; p=3.71E-15) and genotypic model (ORhet=0.43; 95%CIhet: 0.34-0.55 and ORhom=0.22; 95%CIhom: 0.10-0.51; p=1.7E-14). rs1563834, located in the HMGA2 gene, was significant in the allelic (OR=0.4; 95%CI: 0.31-0.52; p=5.48E-13), dominant (OR= 0.35; 95%CI: 0.26-0.46; p=2.96E-14) and genotypic model (ORhet= 0.34; 95%CIhet: 0.25-0.45 and ORhom= 0.48; 95%CIhom: 0.22-1.05; p=2.4E-13).

Conclusion

Three novel loci implicated in lung cancer susceptibility have been identified through a case-control GWAS approach. The associated genes may have a role in tumourigenesis: the PRDM family of genes are deregulated in solid tumours (4); epigenetic silencing of the tumour suppressor ZNF382 is observed in diverse cancer subtypes (5); and HMGA2 was overexpressed in a NSCLC study (6). The identified SNPs may be of prognostic or diagnostic utility.