High-resolution HLA-DRB1 and DQB1 genotyping in Japanese patients with testicular germ cell carcinoma

Abstract

Summary We report for the first time the frequency distributions of HLA-DRB1 and -DQB1 genes in 55 patients with testicular germ cell carcinoma (TGC) using the modified PCR-RFLP method and compare the results with those for 1216 healthy Japanese control subjects. The modified PCR-RFLP method produced accurate, reproducible cleavage patterns that are easily discriminated. HLA-DRB1*0410 was the susceptibility allele (RR = 3.26, P = 0.006) and DQB1 *0602 appears to be a candidate protective allele (RR = 0.26, P = 0.02) for TGC in the Japanese. None of the HLA-DRB1 and -DQB1 alleles showed a specific tendency for histological type or clinical stage of the tumours. Previous studies based on serotyping methods failed to show these allelic associations. High-resolution genotyping is essential because the peptide-binding domain of MHC class 11 molecules is determined more precisely by their genotypes than by their serotypes. In addition, inherent technical difficulties and typing errors of up to 25% make serotyping inefficient. Our results suggest that high-resolution genotyping is a useful genetic marker to determine risk for TGC.Keywords: testicular germ cell carcinoma; MHC class 11 genotyping; modified PCR-RFLP; allele frequency Testicular germ cell carcinoma (TGC), although relatively rare in the male population in general, is the most common malignancy in men between the ages of 15 and 35 years. Strong evidence for the involvement of genetic factors has been reported in TGC development. The incidence of TGC in first degree relatives is 2.2%, and in unrelated individuals 0.4%. For an individual who has a father or brother with TGC, the relative risk of developing TGC is increased sixfold compared with men in the general population. The concordance of tumour histology is high in twins and low in father-son pairs (Tolerud et al, 1985). Moreover, the incidence of TGC is relatively high among white American men in comparison with black American or Oriental men living in the same geographical areas

Pilot Study of the Association between the HLA Region and Testicular Carcinoma among Croatian Patients

“…This is not in concordance with the published data which indicated an increase in HLA-DQ4 antigen frequency as well as the increased frequency of HLA-DRB1*0405 and HLA-DQB1*0401 alleles among patients [15]. Recently, a high-resolution genotyping study in TGCT patients indicated HLA-DRB1*0410 (OR = 3.26) as a susceptibility allele and HLA-DQB1*0602 as a candidate protective allele (OR = 0.26) for TGCT [16]. We did not find an association between these alleles and TGCT in our group of patients.…”

Weighting in the regression analysis of survey data with a cross‐national application

“…To date, linkage studies on these regions have isolated only Xq27 as the locus for a gene (TGCT1) that may be responsible for familial clustering of testicular carcinoma 4. It is not clear whether the HLA regions harbor a hereditary testicular carcinoma gene: The data are controversial 27–33…”

Syndromic aspects of testicular carcinoma

“…4 It is not clear whether the HLA regions harbor a hereditary testicular carcinoma gene: The data are controversial. [27][28][29][30][31][32][33] Table 1 shows whether the genetic defects associated with the hereditary conditions lie in chromosomal regions that appear to be of interest in cytogenetic studies on testicular carcinoma. If there are correlations, then this may be another clue to a causal relation between testicular carcinoma and the genetic defect concerned.…”