Physical activity across the lifespan and liver cancer incidence in the NIH‐AARP Diet and Health Study cohort

Abstract

While liver cancer rates in the United States are increasing, 5‐year survival is only 17.6%, underscoring the importance of prevention. Physical activity has been associated with lower risk of developing liver cancer, but most studies assess physical activity only at a single point in time, often in midlife. We utilized physical activity data from 296,661 men and women in the NIH‐AARP Diet and Health Study cohort to test whether physical activity patterns over the life course could elucidate the importance of timing of physical activity on liver cancer risk. We used group modeling of longitudinal data to create physical activity trajectories using four time points across the life course from teenage years through middle age, identifying seven distinct trajectories. We then used Cox proportional hazards regression to assess the association between the physical activity trajectories and risk of hepatocellular carcinoma, the most common type of liver cancer. We found that, in adjusted analyses, compared to those with consistently low physical activity patterns, those who maintained activity levels over time had a 26–36% lower risk of liver cancer and those who increased physical activity over time had no associations with risk, while those who decreased activity over time had a nonsignificantly higher risk of liver cancer. Our results suggest that sustained physical activity is associated with lower risk of hepatocellular carcinoma, while increasing physical activity later in life may not yield the same benefit. Future research with larger sample sizes and more detailed data on dose and timing of physical activity may continue to yield insight into this association between physical activity and liver cancer risk.

Physical Activity and the Risk of Liver Cancer: A Systematic Review and Meta-Analysis of Prospective Studies and a Bias Analysis

“…Among the 22 reviewed publications, studies (with possible overlap) were excluded from the primary meta-analysis on physical activity and liver cancer if the exposure variable was not physical activity (n = 6) [32][33][34][35][36][37], or if the outcome was not liver cancer (n = 1) [19]; or the effect estimates for physical activity were not shown (n= 4) [32,33,37,38]. Additionally, studies were excluded, if the study design was not prospective (n=5) [39][40][41][42][43], or if the article had a shorter follow-up or fewer events than another publication from the same study (n=5) [16,37,[44][45][46]. in Europe, and four in Asian countries.…”

Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study

“…We performed sensitivity analyses to address potential selection bias, differences in case ascertainment between centers, and additional unobserved confounding. Although HBV and HCV are considered among the strongest risk factors for HCC [3], previous studies [8][9][10][11][12][13]37] were unable to adjust for HBV and HCV. In the EPIC nested case control study the size and direction of the effect size for the association of physical activity and HCC was similar to that of the entire EPIC cohort; however, it was not statistically significant.…”

“…Physical activity and anthropometric measures were assessed only once at baseline. [9] revealed that consistent participation in physical activity throughout the life course might be needed to reduce the risk of liver cancer incidence. We performed mediation analysis for indirect effects acting through general and central obesity, but we were unable to study trajectories of physical activity and body weight that could help to better separate the role of obesity as a confounder and mediator of the association of physical activity and risk of hepatobiliary cancer [8].…”

“…The Physical Activity Collaboration of the National Cancer Institute's Cohort Consortium performed a pooled analysis of 10 prospective US and European cohorts and found that high compared to low leisure-time physical activity was associated with a 27% lower risk of liver cancer incidence [8]. Other prospective studies from the US and East Asian countries support an association of physical activity and lower risk of hepatobiliary cancers [8][9][10][11][12][13]. However, the World Cancer Research Fund International judged that the evidence was not convincing to support an effect of physical activity on liver cancer [14].…”

Update in global trends and aetiology of hepatocellular carcinoma

“…The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 477,206 patients from all over Europe and demonstrated an inverse association between total fat intake (per 10 g/day hazards ratio [HR] = 0.80; 95% CI = 0.65–0.99), while there was no association with meat intake [ 69 ]. The NIH-AARP study, which prospectively enrolled almost 500,000 men and women, reported an increased risk for HCC associated with intake of saturated fat and red meat [ 70 ]. A prospective, randomised, controlled trial in postmenopausal women could not show any beneficial effect of a low-fat diet on the incidence of liver cancer (HR = 0.95, 95% CI = 0.89–1.01; p = 0.10) [ 71 ].…”