Common and novel haplotype structures between different types of cancer

Background

Background: Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with cancer risk. GWAS data are important for cancer prevention and understanding the underlying mechanisms of cancer.

Aims

This study aimed to investigate the genetic association between different types of cancer using GWAS data and a bioinformatics approach.

Methods and results

The significant GWAS variants associated with more than one cancer type were identified. Common linkage disequilibrium (LD) variants between different types of cancer were identified by 1000 genomes phase 3 LD data. Haplotype blocks were identified by analyzing 1000 Genomes phase 3 genotyping data in the GWAS populations. Subsequent analyses included functional SNP analyses and TCGA gene expression. The results associated with significant GWAS variants (P<5E-8) showed the following haplotype associations in European population: GT rs4808075-rs8170 haplotype on BABAM1 with breast and ovarian cancers, GC rs16857609-rs11693806 haplotype on DIRC3 with breast and thyroid cancers, GCG rs380286-rs401681-rs31487 haplotype on CLPTM1L with skin and lung cancers, GGG rs4430796-rs11651052-rs11263763 haplotype on HNF1B with prostate and endometrial cancers, and GT rs10505477-rs6983267 haplotype on CASC8 associated with colorectal and prostate cancers. All these genes had significantly different expressions in tumor tissues (P<1E-3). In addition, the rs11693806 variant is located in the hsa-miR-873-5p binding site and has an enhancing effect on the hsa-miR-873-5p:DIRC3 interaction.

Conclusion

These novel haplotype structures and miRNA:lncRNA interactions are important for understanding the common genetic link between cancers. These results can potentially be used in genetic panels.