Adolescent fitness lowers cancer risk in adulthood

High cardiorespiratory fitness during adolescence appears to provide protection against cancer development and death in late adulthood, suggests a study. This finding is consistent in sibling comparisons.

"However, the influence of unobserved familial confounding appeared to vary by cancer type and be more pronounced for cancer diagnoses than for mortality,” the researchers said. 

“This may suggest a need for robust causal methods to triangulate results, rather than relying on correlations alone, to better inform public health efforts,” they added.

The research team followed 1,124,049 men (mean age at baseline 18.3 years), including 477,453 full siblings, until a median age of 55.9 years. Of these individuals, 98,410 had a cancer diagnosis, while 16,789 died from the disease. [PLoS Med 2025;22:e1004597]

The risk of overall cancer mortality was lower among individuals in the highest quartile of cardiorespiratory fitness (adjusted hazard ratio [HR], 0.71, 95 percent confidence interval [CI], 0.67–0.76; p<0.001) than those in the lowest quartile. This corresponded to a standardized cumulative incidence difference of –0.85 percentage points (95 percent CI, –1.00 to –0.71) at age 65 years.

In addition, individuals in the highest quartile of fitness were less likely to develop rectum, head and neck, bladder, stomach, pancreas, colon, kidney, liver, bile ducts, gallbladder, oesophagus, and lung cancers compared with those in the lowest quartile (HRs ranging from 0.81 to 0.49; incidence differences ranging from –0.13 to –0.32 percentage points; p<0.001 for all).

However, participants in the highest quartile of fitness were found to be at greater risks of prostate (HR, 1.10, 95 percent CI, 1.05–1.16; p<0.001; incidence difference, 0.48 percentage points, 95 percent CI, 0.23–0.73) and skin cancer (eg, nonmelanoma; HR, 1.44, 95 percent CI, 1.38–1.50; p<0.001; incidence difference, 1.84 percentage points, 95 percent CI, 1.62–2.05).

The highest quartile of fitness was also associated with a greater risk of overall cancer diagnosis (HR, 1.08, 95 percent CI, 1.06–1.11; p<0.001; incidence difference, 1.32 percentage points, 95 percent CI, 0.94–1.70), driven primarily by prostate and skin cancer.

Sibling comparisons

In full sibling comparisons, controlled for unobserved shared confounders, the reduction in overall cancer mortality risk persisted (HR, 0.78, 95 percent CI, 0.68–0.89; p<0.001; incidence difference, –0.61 percentage points, 95 percent CI, –0.93 to –0.28). 

On the other hand, the increased risks seen for prostate (HR, 1.01, 95 percent CI, 0.90–1.13; p=0.0867; incidence difference, 0.05 percentage points, 95 percent CI, –0.50 to 0.60), skin (HR, 1.09, 95 percent CI, 0.99–1.20; p=0.097; incidence difference, 0.40 percentage points, 95 percent CI, –0.07 to 0.87), and overall cancer diagnosis (HR, 1.00, 95 percent CI, 0.95–1.06; p=0.921; incidence difference, 0.04 percentage points, 95 percent CI, –0.80 to 0.88) decreased to nearly none.

Sibling comparison results varied for other site-specific cancers, with more decreases for melanoma, kidney, stomach, bladder, pancreas, and liver, bile ducts, and gallbladder cancer. In contrast, associations with lung, colon, head and neck, and oesophagus cancer decreased less. Sensitivity analyses confirmed these findings.

“[E]pidemiological studies on cardiorespiratory fitness and cancer might yield biased conclusions if not conducted carefully, especially considering the bias appears to vary if one considers mortality or diagnosis, and that the associations with different cancer types may be biased to different degrees,” the researchers said.

This sibling-controlled cohort study used registry on all Swedish men who participated in mandatory military conscription examinations from 1972 to 1995 and completed standardized cardiorespiratory fitness testing.

The researchers assessed outcomes such as overall cancer diagnosis and cancer mortality, as well as 14 site-specific cancers, confirmed using the National Patient Register and Cause of Death Register until 31 December 2023.

“The main limitations of this study include the lack of inclusion of female participants, lack of data on other risk factors such as smoking, alcohol consumption, and physical activity, and only adjustment for the unobserved confounders which are shared between full siblings,” they said.