Proteomic aging in adults before and after cancer diagnosis

PROJECT SUMMARY Cancer survivors experience age-related diseases at earlier age than cancer-free persons, suggesting that cancer survivors have accelerated aging. Accelerated aging among cancer survivors could be caused by cancer treatment, but it could also be related to immune response and chronic inflammation. Chronic inflammation is also found in individuals who subsequently develop cancer with subsequent risk of cancer development, and it is possible that accelerated aging starts even before cancer diagnosis. To assess biological aging before and after cancer diagnosis, we will use existing proteomic data and construct and validate proteomic aging clocks in the prospective population-based Atherosclerosis Risk in the Community (ARIC) cohort. The proteins have been already measured three times over 20 years using highly sensitive SomaScan assay. The proteomic aging clocks will be externally validated in the Multi-Ethnic Study of Atherosclerosis (MESA). The strengths of proteomic aging clocks are that these clocks are easily measured, accurately predict biological aging, and are associated with age-related diseases and mortality. However, it is unknown whether proteomic aging clocks predict cancer risk or outcomes in cancer survivors, and there is no agreement about the optimal clock in the context of cancer. To overcome this gap in knowledge, we will construct and validate proteomic aging clocks in ARIC participants who are cancer free but may have other conditions, i.e. these clocks will be cancer-specific proteomic aging clocks (so called, CaPACs). In addition, we will examine the previously published and validated proteomic aging clocks. Our central hypothesis is that accelerated aging is associated with (1) increased cancer risk in persons who are cancer-free at baseline and (2) premature mortality and morbidity among cancer survivors at middle and later age. In the first aim, we will examine the associations between age acceleration for all CaPACs and the risk of overall cancer and specific cancer types in ARIC and MESA. The associations will be also stratified by sex and race. In the second aim, we will examine associations between age acceleration for all CaPACs and all-cause mortality, mortality from causes other than their index cancer, and frailty among cancer survivors in ARIC. In addition, we will compare associations with mortality among cancer survivors and those without cancer history. The use of existing data from the ARIC and MESA studies will allow for quick and cost-efficient testing of our hypothesis. The quantification of proteomic aging in cancer is clinically important because the knowledge of biological age will not only inform risk-stratified cancer screening and post-diagnosis cancer surveillance, but also facilitate the development of anti-aging drugs. 1