Familial Nasopharyngeal Carcinoma 6

56 P-J. Lou, W-L. Hsu, Y-C. Chien et al.relative risk comparing NPC cases and communitycontrols was 176, 63, and 41, respectively, for anti-EBNA-1, anti-EBV VCA IgA, and anti-EBV DNase.5.3.4Case-Control Studies on NPC and EBV DNAin SerumSeveral recent studies have compared EBV DNA inserum/plasma samples of NPC patients and theircontrols. In a cross-sectional case-control study of 42NPC patients and 82 normal controls in Thailand(Mutirangura et al. 1998), the seroprevalence ofEBV DNA (EBNA-2) was 31% for NPC patients and0% for healthy controls. In another cross-sectionalcase-control study of 57 NPC patients and 43 familycontrols in Hong Kong (Lo et al. 1999b), seroprevalenceof EBV DNA (Bam HI-W and EBNA-1) was96% for cases and 7% (3/43) for controls. In the othercross-sectional case-control study of 139 NPCpatients and 178 healthy controls in Hong Kong(Leung et al. 2004), the seroprevalence of EBV DNAwas 95% for NPC patients and 2% for healthy controlsshowing a crude relative risk of 180.In a cross-sectional case-control study of 99patients with advanced NPC, 20 cured NPC patientsand 40 healthy controls in Taiwan (Lin et al. 2004),the seroprevalence of EBV DNA (Bam HI-W) was94% for advanced NPC patients and 0% for curedNPC patients and healthy controls. The moreadvanced the NPC stage, the higher the plasma levelsof EBV DNA. In another cross-sectional case-controlstudy of 124 NPC patients (93 pretreatment, 13relapsed, and 18 in remission) and 40 controls inHong Kong (Fan et al. 2004), the seroprevalence ofEBV DNA was 69% for untreated NPC patients, 85%for relapsed NPC patients, 0% for remission patients,and 2.5% for healthy controls. The more advancedthe NPC stage, the higher the positive prevalence andthe mean level of EBV DNA.5.3.5Cohort Studies on NPC and Anti-EBVSeromarkersIn a 13-year follow-up study of 9,699 men in Taiwan(Chien et al. 2001), both anti-EBV VCA IgA and anti-EBV DNase tested at study entry were significantlyassociated with the risk of NPC developed duringthe follow-up. After adjustment for age and familyNPC history, the relative risk (95% CI) of developingNPC was 22.0 (7.3–66.9) for anti-EBV VCA IgAseropositivityand 3.5 (1.4–8.7) for anti-EBV DNaseseropositivity.Compared with those who wereseronegative for both anti-EBV markers as the referencegroup, the adjusted relative risk (95% CI) was32.8 (7.3–147.2) for those who were seropositive forboth anti-EBV markers. In another cohort study of3,093 anti-EBV VCA IgA-seropositive and 38,955seronegative participants in southern China (Ji et al.2007), seropositivity of anti-EBV VCA IgA was associatedwith an increased risk of NPC during followup,showing a crude relative risk of 9.4. However, theschedule and method for follow-up and NPC ascertainmentwere different between anti-EBV- seropositivesand seronegatives.5.3.6Sensitivity and Specificity of EBV Seromarkersfor NPC ScreeningAnti-EBV VCA IgA was reported to be a sensitive andspecific seromarker for the screening of NPC inendemic areas like Taiwan (Zeng et al. 1982, 1983,1985). The sensitivity and specificity of EBV seromarkersfor the screening of NPC in studies publishedafter 1997 are shown in Table 5.1. Both thesensitivity and specificity vary by seromarker type,laboratory method, cutoff point, geographical area,NPC stage, and control group. The sensitivity of anti-EBV VCA IgA (FA test) and anti-EBV DNase (ELISAtest) for the screening of NPC in Taiwan was 74 and72%, respectively (Liu et al. 1997). The combinationof these two seromarkers increased the sensitivity to88%. In another study in Taiwan (Hsu et al. 2001), thecombination of IgA antibodies against EBV EA andEBNA1 (ELISA test) had the sensitivity and specificityof 98%, and 82%, respectively.In a study comparing the sensitivity and specificityfor NPC screening among anti-EBV Rta, anti-EBVVCA IgA, and anti-EBV EA IgA in Singapore (Fenget al. 2001), the sensitivity was highest for anti-EBVEA IgA (96%) and the specificity was highest for anti-EBV VCA IgA (98%). However, another study comparingthe sensitivity and specificity for NPCscreening among anti-EBV TK, anti-EBV VCA IgA,and anti-EBV EA IgA in China (Connolly et al.2001), anti-EBV TK had the highest sensitivity (96%)and both anti-EBV VCA IgA and anti-EBV EA IgAhad higher specificity (98%). In another study inChina (Cheng et al. 2002), the combination of