Genetic susceptibility to cervical and gastric cancer

Sammanfattning: Cervical and gastric cancer both to a large extent depend on infectious agents. Cervical infection with human papilloma virus increases the risk for cervical cancer substantially, and infection with the bacteria Helicobacter pylori increases the risk for gastric cancer. Both types of infection are far more common than the types of cancer they are associated to, indicating that other factors are involved in the development of cervical and gastric cancer.The hypothesis of this thesis can be put as a question: Do inherited genetic variationmodify the risk for these forms of cancer, either independently of, or interactively with thepathogen? This hypothesis has been tested by genetic epidemiological studies on cervicalcancer, and by association studies on cervical as well as gastric cancer.Familial clustering is a prerequisite for involvement of inherited genetic factors to adisease. In this thesis evidence is presented for a significant familial clustering of cervicalcancer. This familial clustering was found to be restricted to biological relatives. No familialclustering was found for adoptive relatives. The pattern of familial clustering among firstdegree-, second degree-, and adoptive relations have been interpreted as evidence for geneticsusceptibility to cervical cancer. The heritability of cervical cancer was estimated to 27%.Possible stages of the disease development process during which inherited genotypes couldinfluence the risk of cervical cancer, are discussed.To test whether a candidate mutator-gene, hMLH1, is involved in the development ofcervical cancer, DNA from micro-dissected tumours was used for a loss of heterozygositystudy. Allelic loss of hMLH1 was not found to be necessary for cervical cancer development.DNA from epithelial or blood cells, harvested from cancer cases and controls, was usedin genetic association studies on cervical and gastric cancer. A previously reported genetic.association with cervical cancer is disputed, while significant associations between certain HLA alleles and gastric cancer are supported.