Familial Nasopharyngeal Carcinoma 6

Familial Nasopharyngeal Carcinoma 6Kwok Seng LohCONTENTS6.1 Introduction 656.2 Definition 666.3 Causal Associations in Familial NPC 666.3.1 Risks of NPC in First-DegreeRelatives 666.3.2 Genetic Associations in Familial NPC 676.3.3 Non-Genetic Associations inFamilial NPC 676.4 Clinical Manifestation ofFamilial NPC 686.5 Clinical Significance of Familial NPC 696.6 Summary 69References 69Familial nasopharyngeal carcinoma (NPC) is definedas NPC occurring in two or more first-degree relatives.The rate of familial NPC is likely to be about8% in any cohort of NPC patients in a high-riskregion. The risk of a first-degree relative of an NPCpatient being diagnosed with NPC is 2–15 times thatof the general population in the endemic regions.Genetic factors are most likely the major causalassociations for familial NPC, though environmentalfactors cannot be excluded. The current evidenceshows that familial NPC is not a clinical syndrome.Treatment outcomes of familial NPC patients are notestablished and hence the protocols used for managingthese patients should not be different from thesporadic NPC patients. Screening the first-degreerelatives of NPC patients may increase the proportionof early NPC in a high-risk population.6.1IntroductionKwok Seng Loh, MD, FRCSDepartment of Otolaryngology Head & Neck Surgery,National University Health System, 5 Lower Kent Ridge Road,Singapore 119074, Republic of SingaporeNasopharyngeal carcinoma (NPC) is the most commonlydiagnosed head and neck cancer in South EastAsia. The vast majority of the newly diagnosed casesare sporadic without family history of NPC. However,it is well recognized that NPC does occur in familiesin the endemic regions (Loh et al. 2006; Jia et al.2004; Ng et al. 2009; Zeng 2002). In addition, familialNPC is a well-reported entity in the nonendemicregions such as United States, though most of theseare case reports of small number of familial clusters(Nevo et al. 1971; Williams and De-The 1974;Brown et al. 1976; Lanier et al. 1979; Gajwani et al.1980; Fischer et al. 1984; Coffin et al. 1991; Levineet al. 1992; Albeck et al. 1993). Although informationon NPC that exists in multiple members of the samefamily began to emerge in the past two decades,knowledge on familial NPC remains limited. One will