Epstein-Barr virus immune response in high-risk nasopharyngeal carcinoma families in Greenland.

Undifferentiated nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV) infection. Presence of EBV IgA antibodies is rare among healthy individuals and is used as a marker of nasopharyngeal carcinoma in high-incidence populations. Reasons for EBV IgA seropositivity are unknown, but high EBV IgA levels have been found among unaffected close family members and spouses to nasopharyngeal carcinoma patients in Chinese populations. In Greenland, a nasopharyngeal carcinoma-high-incidence area, we compared EBV serology and viral load in high-risk nasopharyngeal carcinoma family members (N = 20) and controls without nasopharyngeal carcinoma-affected relatives (N = 90). There was no significant difference in EBV viral loads between relatives and controls, and EBV was detected in plasma in 5.0% of relatives and 11.4% of controls. There was no significant difference in EBV serology, but the seroprevalence of EBV viral capsid antigen (VCA) IgA was high in both relatives (25.0%) and controls (20.5%). Compared with anti-VCA IgA-negative, anti-VCA IgA-positive individuals had significantly higher EBV viral loads in peripheral blood mononuclear cells (PBMCs) (P < 0.01). The very high prevalence of anti-VCA IgA indicates that this antibody is unsuitable for nasopharyngeal carcinoma screening among Inuits.

Cancer susceptibility in nasopharyngeal carcinoma families--a population-based cohort study.

Undifferentiated nasopharyngeal carcinoma is a result of environmental factors, in particular EBV infection, affecting genetically susceptible individuals. The familial risk of nasopharyngeal carcinoma is among the highest of any malignancy. Whether this susceptibility is restricted to nasopharyngeal carcinoma is unknown as information on the risk of other cancers in relatives is limited. We did a population-based study of the cancer incidence in nasopharyngeal carcinoma families in Greenland, a nasopharyngeal carcinoma-endemic area. Using population-based registers, a cohort of all persons born in Greenland was followed from 1973 to 2002. In this cohort, 134 individuals developed nasopharyngeal carcinoma and their relatives were identified through registers and interviews. Subsequently, the occurrence of cancer was determined by linkage to the population-based cancer register and the risk of cancer in nasopharyngeal carcinoma relatives and nonrelatives compared by relative risks. Among 766 first-degree relatives, the relative risk of nasopharyngeal carcinoma following the family index case was 8.0 [95% confidence interval (95% CI), 4.1-14.0]. Sex and age of the relative or the index case had no modifying effect on the familial risk of nasopharyngeal carcinoma. The relative risks of carcinoma of the salivary glands, 8.4 (95% CI, 2.7-19.5), and uterine cervix, 2.2 (95% CI, 1.1-3.9), were also significantly increased. In families with multiple cases of nasopharyngeal carcinoma, the risk of other cancers than nasopharyngeal carcinoma was further increased. These results indicate that the increased risk of cancer in nasopharyngeal carcinoma families is not restricted to nasopharyngeal carcinoma, but extends to the virally associated cancers of the salivary glands and cervical uteri.