Nasopharyngeal carcinoma (NPC) is a rare disease in most countries throughout the world (1/100,000)), but it occurs at up to a 100-fold higher frequency in the Chinese people of southern China and Southeast Asia. The high incidence also appears in immigrant Chinese. Family history is known to be a very important risk factor for NPC. To investigate the potential genetic component genetic component for susceptibility, a family study of NPC was carried out in Taiwan by Dr. Yue-Fen Wang prior to joining the MEDIB. Detailed information about family history of cancer, smoking habits, and consumption of salted fish during childhood was collected from 750 NPC probands. Segregation analysis of a truncated trait with a logistic probability density function for age of onset was performed. Results suggest that familial clustering of NPC can be best explained by a Mendelian recessive locus with gender specific susceptibility, where consumption of salted fish during childhood and the number unaffected preceding sibs also affects risk. Under this model, the frequency of the high risk allele was 0.18, and the lifetime susceptibility of NPC was 0.09 for females and 0.18 for males with the high risk genotype. Penetrance of this putative high risk genotype by age 80 is 8% for females and 16% for males, compared to 0.04% for females and 0.07% for males with low risk genotypes. Individuals who consumed salted fish during childhood have a slightly higher penetrance (8/8% for females, and 17.2% for males by age 80 for the high risk genotype). The best- fitting model suggests that the high risk gene accounts for over 90% of NPC in this population.
