Genome-wide linkage search for cancer susceptibility loci in a cohort of non BRCA1/2 families in Sri Lanka

Abstract

Objective Although linkage studies have been utilized for the identification of variants associated with cancer in the world, little is known about their role in non BRCA1/2 individuals in the Sri Lankans. Hence we performed linkage analysis to identify susceptibility loci related to the inherited risk of cancer in a cohort of Sri Lankans affected with hereditary breast cancer. The Illumina global screening array having 654,027 single nucleotide polymorphism markers was performed in four families, in which at least three individuals within third degree relatives were affected by breast cancer. Two-point parametric linkage analysis was conducted assuming disease allele frequency of 1%. Penetrance was set at 90% for carriers with a 10% phenocopy rate. Results Thirty-one variants exhibited genome-wide suggestive HLODs. The top overall HLOD score was at rs1856277, an intronic variant in MYO16 on chromosome 13. The two most informative families also suggested several candidate linked loci in genes, including ERAP1, RPRM, WWOX, CDH1, EXOC1, HUS1B, STIM1 and TUSC1. This study provides the first step in identifying germline variants that may be involved in risk of cancer in cancer-aggregated non-BRCA1/2 families from the understudied Sri Lankan population. Several candidate linked regions showed suggestive evidence of linkage to cancer risk.

Transcriptional Dysregulations of Seven Non-Differentially Expressed Genes as Biomarkers of Metastatic Colon Cancer

“…EXOC1 is the gene exocyst complex component 1 and is involved in cell migration, similar to Sections 5 and 8 [ 42 ]. No literature was found that supports the connection between EXOC1 and CC; however, genetic mutations in EXOC1 have been associated with breast and cervical cancer [ 46 , 47 ]. Combining our experimental data and the literature evidence, EXOC1 may be inferred as a dark biomarker of mCC due to its involvement in cell migration processes, and transcriptomics may not be the ideal technology to investigate its functional roles.…”