Familial Nasopharyngeal Carcinoma 6

66 K. S. Lohobviously surmise that with multiple members in afamily diagnosed with NPC, genetic factors must playa leading role. However, epidemiological and clinicalevidences have demonstrated that genetic factorsalone might be just one of the several causative factorsfor familial NPC (Jia et al. 2005). It is generallyaccepted that the carcinogenesis of NPC is the interplaybetween genetic and environmental factors andthe Epstein–Barr virus. Thus, shared environmentalfactors may also be responsible for NPC occurring infamilies.NPC observed in multiple members of a singlefamily is not uncommon. Comparing with other commonlydiagnosed malignancies such as colorectalcancer, the probability of NPC diagnosed in siblingsis higher. Clearly, familial NPC is not likely to be arandom entity. Understanding of the pathogenesis aswell as clinical manifestation may lead to early detectionand the development of an effective and efficientscreening program in high-risk populations.6.2DefinitionThe National Cancer Institute (NCI) of the UnitedStates defined familial cancers as cancers occurringin families more often than would be expected bychance. Classic examples of cancers fulfilling thisdefinition include retinoblastoma, familial medullarycarcinoma, and certain forms of breast, ovarian,and colon cancers. The connotation of familial canceris that inheritable factors are responsible for itsoccurrence. However, even in the stated list of examplesof familial cancers, not all are absolutely familialbut may occur in a sporadic manner. Furthermore,there is no internationally accepted definition forfamilial NPC.Familial cancers are best described as cancersthat occur within a family related by shared geneticcomponents. For simplicity, familial NPC may bedefined as NPC occurring in two or more first-degreerelatives of a family. First-degree relatives within afamily include parents, children (offspring of theparents), and siblings from the same parents. Firstdegreerelatives are not only genetically related butalso more likely to share common environmentalfactors. Most cases reported in the literature definefamilial NPC as a disease entity if two or more firstdegreerelatives within a family are affected by NPC(Loh et al. 2006; Jia et al. 2004; Zeng et al. 2002;Chen et al. 1990; Ung et al. 1999).6.3Causal Associations in Familial NPC6.3.1Risks of NPC in First-Degree RelativesIt is tempting to attribute familial NPC to genetic factorsalone; however, such an assumption could onlybe true if most first- or second-degree relatives in thesame family are also diagnosed with NPC. In othercommonly diagnosed malignancies with a predilectionfor familial aggregation such as colorectal andbreast cancers, the incidence of the same pathologydiagnosed in the same family is relatively high(Hemminki et al. 2004). The rate of familial NPC inany cohort is very likely to fall between 2 and 15%,and most reports suggest a rate varying from 6 to 8%(Table 6.1) (Loh et al. 2006; Chen and Huang 1997;Yu et al. 1990; Yuan et al. 2000). Although such rate ishigher than many other types of familial cancers, theincidence of 2–15% is not sufficient to suggest thatgenetic factors play the only role. It is suggested thatshared environmental factors such as diet can alsoexplain the rate of familial aggregation in NPC (Yuet al. 1986).The discrepancies between the incidences reportedin the above-mentioned studies need further discussion.The incidence of familial NPC reported in certainendemic regions such as Singapore was substantiallyhigher than other countries or regions. The underlyingreason for this high incidence is not clear. However,a study reported from China for patients with intermediate-riskfor NPC, i.e., patients of nonendemicareas of China origin demonstrated a low incidence offamilial NPC (Yuan et al. 2000). If only the series ofpatients from high-risk regions were reviewed, morethan 8.3% of NPC are familial (Table 6.1). Therefore,the risk of familial NPC probably is associated withTable 6.1. Familial NPC rates in different studiesStudy Region Cohort RateLoh et al. (2006) Singapore 200 31/200, 15.5%Yuan et al. (2000) Shanghai 918 17/918, 1.9%Ung et al. (1999) Taiwan 375 25/375, 6.7%Chen et al. (1997) Hong Kong 104 8/104, 7.7%Yu et al. (1990) Guangzhou 306 18/306, 5.9%