A nested case–control study of risk factors for adult T-cell leukemia/lymphoma among human T-cell lymphotropic virus type-I carriers in Japan

Objectives: The purpose of this study was to investigate the serological risk factors for development of adult T-cell leukemia/lymphoma (ATL) among human T-cell lymphotropic virus type-I (HTLV-I) carriers. Methods: A nested case–control study was performed. The source population comprised 23,922 subjects who had either visited the outpatient clinic or who had received annual health check-ups at the K Hospital, Nagasaki, Japan, at least once during 1985–1996 (HTLV-I seroprevalence = 16.1%). Markers of HTLV-I infection were examined in stored sera from 29 incident cases of ATL diagnosed during 1985–1997, and 158 controls matched for sex, birth year, date of sample collection, and HTLV-I seropositivity (median follow-up = 6.4 years). Results: In exact conditional logistic regression analysis, high levels of soluble interleukin-2 receptor ( ≥ 500 U/ml) and high HTLV-I antibody titers (≥ 1024) were independently associated with an increased risk of developing ATL (Odds ratio 20.5, 95% confidence interval (CI) 4.5–194 and 2.9, 95% CI 0.98–9.5, respectively). The results remained essentially unchanged when the subjects were restricted to those whose histories were followed for two years or longer. Conclusions: These findings indicate that high soluble interleukin-2 receptor levels and high HTLV-I antibody titers are strong predictors of ATL among carriers of HTLV-I.