Epidemiological studies of host susceptibility in malignant lymphomas and colorectal cancer

Sammanfattning: The aim of this thesis was to investigate the role of host susceptibility in malignant lymphomas and colorectal cancer. Specifically, the associations between infection and malignant lymphomas, skin cancer and survival from subsequent cancer, and the association between inflammatory bowel disease, familial disease, and colorectal cancer were assessed using Swedish population-based and nation-wide registers. To investigate the role of chronic infections in the epidemic increase of non-Hodgkin's lymphomas, 5,199 individuals diagnosed or treated for tuberculosis 1939-1960 were followed-up for cancer occurrence through 1996. Overall, there was a moderately increased risk of nonHodgkin's lymphoma, with particularly elevated risks among patients with severe tuberculosis diagnosed before 1952. The risk of Hodgkin's disease following infectious mononucleosis was assessed in one Swedish cohort of 21,510 individuals hospitalised with infectious mononucleosis 1964-1994, and in one Danish cohort of 17,052 individuals with a positive Paul-Bunnell test 1943-1978. The risk of Hodgkin's disease was more than doubled, increased with age at infectious mononucleosis, decreased with time since infectious mononucleosis, but remained elevated up to 20 years after the infectious mononucleosis. The highest risk was observed in the age-group 15-34 years. The prognostic significance of a history of squamous cell skin cancer was assessed in five cohorts of patients with non-Hodgkin's lymphoma (n=36,629), colon cancer (n=77,039), breast cancer (n=139,767), prostate cancer (n=121,280), or lung cancer (n=60,681). In each cohort, the mortality among patients with a previous registration of squamous cell skin cancer was compared to that of same-site cancer patients without such history. In the cohorts, a history of squamous cell skin cancer was associated with a 20-30% increased risk of death. To assess the significance of familial colorectal cancer and familial inflammatory bowel disease on the risk of colitis-associated colorectal cancer, 19,459 patients with inflammatory bowel disease 1955- 1995 were followed-up for cancer occurrence 1958-1995. Familial colorectal cancer (assessed through record-linkage) was associated with a doubled risk of colitis-associated colorectal cancer, but familial inflammatory bowel disease had no significance. To test the hypothesis of a common genetic determinant for inflammatory bowel disease and colorectal cancer, the risk of colorectal cancer among first-degree relatives of patients with inflammatory bowel disease was assessed. Among 114,102 first-degree relatives, no increased occurrence of colorectal cancer could be detected. The results suggest that tuberculosis and infectious mononucleosis are risk factors for non-Hodgkin's lymphoma and Hodgkin's disease, respectively, that a history of squamous cell skin cancer is a marker of poor survival among patients with cancer, that inflammatory bowel disease and colorectal cancer do not share a common genetic cause, and that familial colorectal cancer (but not familial inflammatory bowel disease) is a risk factor for colitis-associated colorectal cancer.