Familial Nasopharyngeal Carcinoma 6

296 E. Ozyar and I. Ayanmetastasis, fewer WHO Type 1 (keratinizing) tumors,and a better prognosis when compared with adults(Huang 1982).NPC is a malignant tumor with a variable range ofincidence depending on age, ethnicity, and geographiclocalization (Wei and Sham 2005). InSoutheast Asia, where the incidence is the highest inthe world, the incidence of NPC demonstrates a singlepeak at about the age of 50 years (Huang 1982).However, NPC shows a bimodal age distribution innonendemic countries and the first peak is seen inthe second decade in addition to the second peak atmore advanced age (Selek et al. 2005) While the rateof pediatric patients accounts for 6%–18% of all NPCpatients in nonendemic countries like Argentina,Turkey, India, Israel, Morocco, Tunisia, Algeria, andUganda, the rate is reported to be less than 1% of allNPCs in the endemic countries (Zubizarretta et al.2000; Berberoglu et al. 2001; Laskar et al. 2004;Bar-Sela et al. 2005; Cammoun et al. 1974; Ayan Iet al 2003; Sahraoui et al. 1999; Schmauz et al.1972). Although NPC has the highest incidenceworldwide, in Southeast China, first peak does notexist (Sham et al. 1990). The number of patients lessthan 15 years of age is reported to be 53 (0.1%) among54,304 NPC patients treated between 1964 and 1983in Guangdong Province of China, where NPC has thehighest incidence (Huang et al. 1990). However, therate of pediatric cases is reported to be 5% in LiaoningProvince, one of the areas with lowest risk for NPC inChina, from where a retrospective analysis of 117Chinese pediatric or adolescent NPC patients wasreported recently (Cao et al. 2006).Although the incidence of NPC is less frequent inMediterranean basin countries than in Southeast China,there is an additional minor peak between the ages of10 and 20 years besides the second peak at the fifthdecade. There is a significant number of reports in theliterature which reported the treatment results of pediatricand adolescent NPC patients from the Maghrepcountries, Egypt, Israel, and Turkey (Serin et al. 1998;Har-Kedar et al. 1974). A few studies reported a substantialnumber of pediatric NPC in France; however,more than two-thirds of accrued patients were originallyfrom Maghrep countries (Habrand et al. 2004).However, data from Portugal, Italy, and Greece suggestedthat the incidence of pediatric NPC is not as highas in southern and eastern Mediterranean countries(Polychronopoulou et al. 2004).Southern and eastern Mediterranean countrieswith high incidence of pediatric NPC share twoimportant characteristics. They are all developing andare Muslim countries, except Israel, although approximately30% of Israel’s population consists of MuslimArabs. A case-control study was carried out to assessthe genetic and environmental risk factors in Maghrebcountries (Northern Africa countries bordering theMediterranean) by the International Agency forResearch of Cancer (Feng et al. 2007). This study postulatedthat consanguinity (15%–30% of marriages)might have increased the level of genetic homozygozitywhich may have caused a recessive susceptibility.We may partly explain the higher proportion of youngcases observed in the Mediterranean basin countries,especially Muslim countries of this region like Turkey,Morocco, Egypt, Tunisia, and Algeria, when comparedwith the Southeastern Asian countries where consanguinityis socio-culturally rare. However, results ofthis study have shown no significant differencebetween the proportion of cases and controls reportingconsanguinity in parents (18.3% vs. 19.8%, p =0.48) (Feng et al. 2007).In the United States, only 3% of NPC occurs inpatients younger than 19 years of age according toSurveillance, Epidemiology and End Results (SEER)data (Marks et al. 1998), and pediatric NPC is moreprevelant among African-Americans and its geographicdistribution favours southern states (Greene et al.1977). Furthermore, approximately and 38% of thecases in NPC patients younger than 20 years or between20 and 40 years were undifferentiated subtype, respectively,whereas patients older than 40 years were oftendiagnosed with keratinizing squamous cell carcinoma.The randomized study conducted by the PediatricOncology Group (POG) enrolled 18 patients from 59institutions to the POG 9486 study, and majority ofpatients from the United States were from Southeasternor Southern–Midwestern institutions. Among all theaccrued patients, 65% were reportedly of African-American origin (Rodriguez-Galindo et al. 2005).Most of the reports on pediatric NPC have demonstrateda male predominance (Uzel et al. 2001).The largest series in the literature published by theRare Cancer Network (RCN) have shown a male tofemale preponderance of 2:1 in 165 patients (Ozyaret al. 2006).The differences between endemic and nonendemicNPC suggests underlying etiologic variationsbetween children and adults. It is postulated that distinctoncogenic mechanisms exists for the pediatricform of NPC in the literature (Khabir et al. 2003).Major risk factors for NPC include diet, Epstein–Barrvirus (EBV) reactivation, and genetic susceptibility(Jeannel et al. 1999). Common risk factors among