INFLUENCE OF THE MAJOR HISTOCOMPATIBILITY COMPLEX ON AGE AT ONSET OF CHRONIC LYMPHOID LEUKEMIA

The major histocompatibility complex is one of the interactive factors in the multifactorial model of carcinogenesis. Its main influence in experimental models is on the age at onset of malignancies. We have pr eviously shown a similar effect of homozygosity for HLA-DR53 in CML. I n the present study, we investigated 79 patients with CLL and 329 loca l controls from Germany. In addition to full serotyping, all patients and 116 of controls were also typed by HLA-DRB PCR analysis. The homoz ygosity rates for DR53 in patients under and over the median age (60 y ears) were 18.6% and 2.9%, respectively (P = 0.03). Eight of the 9 hom ozygous patients were under the median age. The sex ratio in the DR53 homozygous group was reversed in favour of females. The homozygosity r ates for DR53 were different in the overall groups of patients and con trols, yielding a relative risk (RR) of 2.4 (P = 0.03). This associati on was stronger in the early-onset group compared to age-matched contr ols (RR = 4.4; p = 0.008) and for females with an early onset compared to age- and sex-matched controls (RR = 17.9; p = 0.0008). The simulta neous occurrence of the alleles of the haplotype A2B62DR4 showed a str ong association with CLL (RR = 4.1; p = 0.002). This was probably the reason behind the association with HLA-DRB 10401 (RR = 2.4; p = 0.009 ). Compared to the accelerating effect of HLA-DR53, HLA-DR52 showed a significant delaying effect on the onset of CLL. These findings confir med the influence of the HLA complex on the development of another leu kaemia. (C) 1996 Wiley-Liss, Inc.