We have surveyed the incidence of adult T-cell leukemia/lymphoma (ATLL) in an endemic area of 290,464 inhabitants for 7 years. We now revise our previous results on the basis of additional findings and estimate the age- and sex-specific cumulative rate for HTLV-I carriers, the adoption of which is recommended by current cancer epidemiology as a new age-standardized incidence rate. An unequivocal age-dependent increase in seroprevalence was observed for both sexes with a characteristic predominance in females. The age-dependent seroconversion in females may be partly explained by additional infection from infected husbands to their wives but the reason for men remains obscure. The mean annual number of incident cases of ATLL was 11.4, giving 3.9 ATLL patients annually per 10(5) inhabitants, 6.1 per 10(5) inhabitants aged over 30, and 85.0 per 10(5) seropositives aged over 30. Crude annual incidence rate of ATLL among 10(5) male seropositives aged over 30 was 145.3 and that for females was 55.2 and 95% confidence intervals of ATLL incidence rates were 34.8 to 255.7 for males and 6.4 to 104.1 for females, respectively. Although the sex ratio of 80 ATLL patients was 1.35, males are more prone to the disease (46 male patients among 4,522 male seropositives aged over 30 vs 34 female patients among 8,801 female seropositives aged over 30; p less than 0.001) for unknown reason(s). Morbidity in male seropositives aged over 30 is 2.6 times as high as that of females. Decennial incidence rates in males in their fifties and sixties were significantly higher than those in females. The remarkable male preponderance in oncogenicity of HTLV-I may be due to the fact that men are more prone to the disease and the number of female carriers in the denominator used to calculate the incidence rate is larger than that of males. The whole life span (0-79) cumulative risk for males was 6.9% and significantly higher than that of females (2.95%).

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Chromosome analysis was performed on 1 patient with diffuse lymphoma of mixed type by histologic diagnosis and on 7 patients with the acute type of adult T-cell leukemia (ATL). Specific abnormalities in chromosome 14 at break band q11 with the assigned locus of the alpha-chain gene of the T-cell antigen receptor were identified in 6 of 8 patients. Inv(14) (q11q32) was found in 2 patients and translocation of chromosome 14 at break band q11 was observed in 4. Donor chromosomes involved in translocation of the 14q11 varied, i.e., chromosomes 3, 7 or X, with the exception of one patient whose donor chromosome origin could not be determined. The breakpoint in chromosome 3 was in band p25, a region reported to include the locus of the c-raf-I oncogene. In chromosome 7, it was in band p11, a region reported to include the locus of the c-erb-B oncogene, and in the sex chromosome X, it was in band q11. One patient also had a chromosome 14 aberration at break band q32. Of the 2 remaining patients, one had lost chromosome 14 and the other had an isochromosome 14q. Our observation and other reported findings suggest that the rearrangement of chromosome 14 at break band q11 is specific for lymphoma-type or acute-type ATL patients, and aberrations of proto-oncogene expression or the coding sequence by recombination involving a T-cell antigen receptor gene due to chromosome inversion or chromosome translocation may play an important role in T-cell neoplasia including ATL.

The yearly incidence of ATLL in the Uwajima district is 6.6 patients per 100,000 inhabitants aged over 40. The yearly morbidity rate from ATLL of persons in this district who are positive for HTLV-antibody and older than 40 is 1 patient per 1,631. Familial occurrence was observed in 9/38 families available for pedigree analyses. Even in the endemic area, the existence of positive HTLV antibody is remarkably high in ATLL families, suggesting that HTLV has been transmitted from generation to generation mainly within these particular families.

T lymphocytes of patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) were cultured. After cultivating for several months, HAM-derived cell lines were tested for the presence of HTLV-1 proviral genome. We have found two major subgroups, the SacI type and the PstI type, of HTLV-1 by the restriction map analysis. They were almost equally distributed among HAM patients. We have also found two types of the provirus in DNA derived from fresh peripheral blood lymphocytes (PBL) or lymph node cells of adult T-cell leukemia/lymphoma (ATL) patients. The PstI type proviruses were predominant in ATL patients. It was concluded that two major subgroups of HTLV-1 exist in Japan and both types have an ability to cause either of two diseases, ATL or HAM.