Werner's Syndrome (WS) or adult-onset progeria is an autosomal recessive 
disorder of accelerated aging caused by mutations of the DNA RecQ 
helicase/exonuclease (WRN). WRN is an ATP-dependent helicase with 3' to 5' DNA 
exonuclease activity that regulates the replicative potential of dividing cells, 
and WRN loss-of-function mutations promote cellular senescence and neoplastic 
transformation. These molecular findings translate clinically into adult-onset 
progeria manifested by premature hair graying, dermal atrophy, cardiovascular 
disease, and cancer predilection along with a markedly reduced life expectancy. 
Recently, a patient with WS who developed pancreatic adenocarcinoma was 
identified in Honolulu suggesting a significant prevalence of loss-of-function 
WRN mutations in Hawaii's Japanese-American population. Based upon the 
indigenous Japanese WRN loss-of-function mutation heterozygote rate of 6 per 
1,000, we speculate the possibility of approximately 1,200 heterozygotes in 
Hawaii. Our ongoing studies aim to evaluate Hawaii's true allelic prevalence of 
WRN loss-of-function mutations in the Japanese-American population, and the role 
of WRN silencing in sporadic cancers. In summary, WRN plays a nexus-like role in 
the complex interplay of cellular events that regulate aging, and analysis of 
WRN polymorphisms in Hawaii's population will generate novel insights to advance 
care for age-related pathologies.