Immunogenetics of Cervical Cancer: A Family-Based Design

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DESCRIPTION (provided by applicant): Persistent oncogenic human papillomavirus (HPV) infection in the cervix and cervical neoplasia are marked by a shift away from a cell-mediated (HPV-suppressive) and toward a humoral (HPV-permissive) immune response. Interleukin 12 (IL12) is a cytokine that promotes a cell-mediated response by activating macrophages and natural killer cells and increases the expression of major histocompatibility complex class I cell surface receptors. IL10, on the other hand, suppresses a cell-mediated response by down-regulating the expression of certain cytokines, MHC class II receptors, and co-stimulatory molecules on macrophages. Prior epidemiologic investigations have shown that a family history of cervical cancer is associated with an increased risk of this disease but have not identified specific genes and genetic variants that may be responsible. We hypothesize that variation in the genes encoding the cytokines IL10 and IL12 (IL10, IL12A and IL12B) is associated with invasive cervical cancer risk in women persistently infected with HPV. To test this hypothesis we propose to examine the association between IL10, IL12A, and IL12B single nucleotide polymorphisms and haplotypes and risk of invasive cervical cancer using a family-based study design. We are currently recruiting invasive cervical cancer cases into an on-going population-based case-control study of HPV cofactors and anogenital cancers. In the proposed study, mothers and fathers of 140 invasive cervical cancer cases 18-49 years of age will be recruited into a protocol consisting of blood or buccal cell collection and a telephone interview. We will estimate the relative risk of invasive cervical cancer associated with carriership of 16 polymorphisms (expected to comprise approximately 23 haplotypes) based on the rules of Mendelian genetics. The proposed study will contribute to our understanding of the role of immune response and genetics in invasive cervical cancer etiology, both of which may have a direct impact on vaccine development.