Trade-offs between cancer and other diseases: do they exist and influence longevity?

Relationships between aging, disease risks, and longevity are not yet well understood. For example, joint increases in cancer risk and total survival observed in many human populations and some experimental aging studies may be linked to a trade-off between cancer and aging as well as to the trade-off(s) between cancer and other diseases, and their relative impact is not clear. While the former trade-off (between cancer and aging) received broad attention in aging research, the latter one lacks respective studies, although its understanding is important for developing optimal strategies of increasing both longevity and healthy life span. In this paper, we explore the possibility of trade-offs between risks of cancer and selected major disorders. First, we review current literature suggesting that the trade-offs between cancer and other diseases may exist and be linked to the differential intensity of apoptosis. Then we select relevant disorders for the analysis (acute coronary heart disease [ACHD], stroke, asthma, and Alzheimer disease [AD]) and calculate the risk of cancer among individuals with each of these disorders, and vice versa, using the Framingham Study (5209 individuals) and the National Long Term Care Survey (NLTCS) (38,214 individuals) data. We found a reduction in cancer risk among old (80+) men with stroke and in risk of ACHD among men (50+) with cancer in the Framingham Study. We also found an increase in ACHD and stroke among individuals with cancer, and a reduction in cancer risk among women with AD in the NLTCS. The manifestation of trade-offs between risks of cancer and other diseases thus depended on sex, age, and study population. We discuss factors modulating the potential trade-offs between major disorders in populations, e.g., disease treatments. Further study is needed to clarify possible impact of such trade-offs on longevity.

Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study.

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging risk factor and therapeutic target for cardiovascular disease. The activity and mass of this enzyme are heritable traits, but major genetic determinants have not been explored in a systematic, genome-wide fashion. We carried out a genome-wide association study of Lp-PLA(2) activity and mass in 6,668 Caucasian subjects from the population-based Framingham Heart Study. Clinical data and genotypes from the Affymetrix 550K SNP array were obtained from the open-access Framingham SHARe project. Each polymorphism that passed quality control was tested for associations with Lp-PLA(2) activity and mass using linear mixed models implemented in the R statistical package, accounting for familial correlations, and controlling for age, sex, smoking, lipid-lowering-medication use, and cohort. For Lp-PLA(2) activity, polymorphisms at four independent loci reached genome-wide significance, including the APOE/APOC1 region on chromosome 19 (p = 6 x 10(-24)); CELSR2/PSRC1 on chromosome 1 (p = 3 x 10(-15)); SCARB1 on chromosome 12 (p = 1x10(-8)) and ZNF259/BUD13 in the APOA5/APOA1 gene region on chromosome 11 (p = 4 x 10(-8)). All of these remained significant after accounting for associations with LDL cholesterol, HDL cholesterol, or triglycerides. For Lp-PLA(2) mass, 12 SNPs achieved genome-wide significance, all clustering in a region on chromosome 6p12.3 near the PLA2G7 gene. Our analyses demonstrate that genetic polymorphisms may contribute to inter-individual variation in Lp-PLA(2) activity and mass.