DESCRIPTION (provided by applicant): Rising incidence trends of non-Hodgkin's lymphoma (NHL) have been observed in the Western world during more than four decades; still, the underlying causes for the vast majority of all cases of NHL, and consequently, for the increasing temporal trends, remain unestablished. Different lines of evidence indicate an association between ultraviolet radiation (UVR) exposure and risk of NHL, including increased occurrence of lymphomas in skin cancer patients and vice versa. Average levels of UVR exposure and skin cancer incidence are also known to increase in many populations. DNA repair genotypes relate to the capacity to repair UVR-damaged DNA and to skin cancer susceptibility. We propose to investigate if polymorphisms in genes involved in repair of UVR-damaged DNA are associated also with susceptibility for NHL. We intend to use blood samples collected in a large NIH-supported population-based case-control study, including in total 3 000 NHL cases and 2 800 controls in Sweden and Denmark. Specifically, we plan to analyze if 21 single nucleotide polymorphisms and haplotypes in genes involved mainly in the nucleotide excision repair pathway, are associated with NHL in a subset of 500 cases and 500 controls selected at random. In the case-control study, questionnaire data on UVR exposure has also been collected; therefore, the proposed study will, in addition, give us the unique opportunity to investigate both genetic and environmental aspects of UV exposure in the same individuals in analyses of gene-environment interaction. To our knowledge, genetic variance related to repair of DNA damage, induced for example by UVR, has not been investigated before in association with NHL. Polymorphisms associated with DNA repair capacity may be important markers of the individual's susceptibility to develop NHL, and may also serve as markers of modification of a carcinogenic exposure effects, UVR, for example. In light of the intriguing associations between lymphomas and skin cancer on one hand, and between UVR exposure, DNA repair genotype, and skin cancer on the other, we believe that testing this novel hypothesis might add important biological information to the enigma of NHL etiology.