Abstract:
Objective: Although linkage studies have been utilized for the identifcation 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 afected 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 afected 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 frst 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 sugges‑
tive evidence of linkage to cancer risk.
