br Contribution br Conflicts of interest br Acknowledgements
Conflicts of interest
Acknowledgements Work on this study was supported by the Cancer Information and Population Health Resource, UNC Lineberger Comprehensive Cancer Center, with funding provided by the University Cancer Research Fund via the state of North Carolina, USA (A16-0735).
Introduction Cancer is the second most common cause of death and a leading contributor to serious morbidity, and the incidence of malignant neoplasms is projected to increase by 70% in the coming 20 years . Long-term risk assessments for both cancer incidence and mortality are therefore of great importance, as well as the identification of modifiable factors early in life that may reduce subsequent cancer risk and mortality. Aerobic Tigecycline is a powerful and potentially modifiable marker of health, and a high level of fitness is associated with a reduced risk of multiple diseases and all-cause mortality [2,3]. High levels of aerobic fitness also have been associated with large risk reductions for cancer incidence and cancer-associated mortality [, , , ]. Those who are aerobically fit and are diagnosed with cancer also have an increased rate of survival . The association of aerobic fitness with cancer has primarily been investigated in middle-aged and older populations . In such settings, underlying diseases may lead to problems with residual confounding and reverse causation, distorting the observed associations. In addition, as most study populations consist of middle-aged individuals, they fail to include cancers of young adulthood or examine potentially modifiable predictors at younger ages. It is also important to take familial factors into account in risk assessments over the life-course, as the genetic components of aerobic fitness and cancer are both large [, , ].
Materials and methods
Discussion The contribution of the present study is the use of a large, nationwide cohort with a long follow-up period, validated endpoints and the opportunity to employ a co-sibling design to take familial factors such as genetic factors and a shared environment into account. The main results are in line with previous studies. For example, Lee and colleagues found a strong, inverse relationship between level of aerobic fitness and cancer mortality in middle age . Similarly, Lakoski et al. found that individuals with high aerobic fitness were at a lower risk of cancers of the lung and gastrointestinal tract compared to their less fit counterparts, also in a middle-aged population . As mentioned above, we assessed the effect of Wmax on cancer and cancer-associated mortality for specified time points. This revealed a difference over time: during the first half of the follow-up, i.e., when subjects were aged 18–38 years, high aerobic fitness was either not associated with the risk of cancer or cancer mortality, or it conferred a slightly increased risk. Importantly, this association was attenuated when accounting for familial factors, indicating a confounding by familial factors. Conversely, high aerobic fitness was associated with a decreased risk of cancer and cancer mortality during the second half of the follow-up. This trend may be attributable to the varying share of cancer types for different age groups, as cancers of young adulthood – and thusly those that likely occurred during the first half of the follow-up – are primarily comprised of lymphomas, leukemia and tumors of the central nervous system [17,18]. Robsahm et al. investigated the relationship between aerobic fitness and the risk of site-specific cancers and found no association between level of fitness and the risk of hematological malignancies or tumors of the central nervous system . In contrast, aerobic fitness has been linked to cancers typically diagnosed during and past middle age – predominantly comprised of solid tumors, especially of the lungs and gastrointestinal tract [4,, , ].