Both class I and class II HLA antigens are thyroid cancer susceptibility factors.

It has been established that HLA antigens are susceptibility factors for different cancers, including thyroid tumors. However, the diversity and sometimes weak and contradictory associations found have frequently led to the view that the HLA and tumorigenesis links might be the result of statistical errors. However, it has recently been established that it is indeed a currently complex and unexplained but real phenomenon, which may be crucial in preventing several types of cancer. In the present work we have found in a relatively large series of thyroid cancer patients (n = 161) that both HLA class I (B35) and class II (DR11) antigens are susceptibility factors only in the papillary tumor group of patients, B35 association p value is found at the limit of significance (pc(120) = 0.05); the follicular group did not show any HLA association, suggesting that the etiopathogenesis of each type of cancer is different. HLA-B35 and DR11 are not working together to induce tumorigenesis and each of them seems to confer susceptibility by using different pathways or by being markers of distinct neighboring susceptibility genes. DR4 has also been found in 86% (n = 6) of Hürthle cell carcinoma. No association has been found between HLA and disease activity. HLA mechanisms of association to cancer are discussed and a world-wide HLA/tumorigenic study is proposed to obtain a clear picture of the puzzling and controversial susceptibility markers found in different tumors and in different ethnic groups.