NCI researchers conducted a family-based linkage study of 358 families (3,216) individuals with two or more family members affected with nasopharyngeal cancer (NPC) in Taiwan. This study is the largest family study of NPC to date and is designed to be representative of NPC multiplex families in Taiwan because identification and accrual into the study was based on information obtained via the Taiwan National Tumor Registry. Investigators have shown that unaffected individuals within the families are at over 10-fold increased risk of developing incident NPC over a 5-6 year follow-up period compared to the general population in Taiwan (annual incidence rate approaching 100 per 100,000). Initial virological studies have shown that elevations in anti-EBV antibody levels are associated with a strong increase in risk of NPC over a 5-6 year follow-up period. Although anti-EBV testing is predicted to identify more than 85% of those who subsequently develop NPC (high sensitivity), half of high-risk individuals studied tested positive, suggesting that markers with higher specificity are needed before clinical use. Initial linkage analyses using modest density microsatellite markers did not reveal any significant genetic susceptibility markers. Whole exome sequencing of affected and selected unaffected members from these families is underway to search for rare variants linked to NPC.