There is growing evidence that taller people have an increased risk of colorectal cancer, which is thought to be explained by an increased production of growth hormones during puberty and/or a larger pool of at-risk colonic cells. Long bone growth during puberty is, in part, promoted by insulin-like growth factor-1, a higher circulating level of which is a risk factor for colorectal cancer. Thus, we hypothesized that long-bone growth indicated by leg length would be the component of height that is more strongly associated with colorectal cancer. To address this hypothesis, we evaluated the association of leg length, sitting height and total height with colorectal cancer risk in the Atherosclerosis Risk in Communities (ARIC) prospective cohort.
The ARIC participants included 14,605 men and women who were cancer-free at baseline (1987-1989), and followed until 2006. Information about demographic, lifestyle, and anthropometric characteristics was obtained at baseline. Leg length was estimated as standing height minus sitting height. Incident colorectal cancers (n = 344) were ascertained by linkage to cancer registries and supplemented by hospital records.
Cox proportional hazards regression was used to estimate hazard ratios (HR) of colorectal cancer and 95% confidence intervals (CI) across quartiles of height, leg length, and sitting height. The final models were adjusted for age, sex, race, study center, education level, waist-to-hip ratio, female hormone replacement therapy use, and smoking status.
Participants with longer legs tended to be male, African-American, and had higher education. Leg length was correlated with total (Pearson r = 0.83), and sitting height (Pearson r = 0.52). Participants in the highest quartile of leg length were at a 42% greater risk of colorectal cancer, relative to the lowest quartile (95% CI, 1.01-2.00, p-trend = 0.04). After stratification by gender, leg length remained associated with colorectal cancer risk in men (HR = 1.83, 95% CI, 1.11-3.05) but not in women (HR = 1.14, 95% CI, 0.70-1.83) for the highest versus the lowest quartile of leg length (p-interaction = 0.16). The HRs for the highest quartiles of total height and sitting height compared to the lowest quartiles were also increased, but the associations were weaker (HR = 1.25, 95% CI, 0.90-1.74, p-trend = 0.10 and HR = 1.30, 95% CI, 0.95-1.79, p-trend = 0.18 respectively).
In this prospective study, longer leg length was more strongly associated with an increased risk of colorectal cancer than overall height or sitting height. While we cannot rule out that the association between taller height and colorectal cancer risk may be explained by a larger pool of colonic cells in taller people, these findings support the prior observation that this association is driven by biological mechanisms correlated to long bone growth during puberty, such as insulin-like growth factor-1.
Citation Format: Guillaume C. Onyeaghala, Pamela L. Lutsey, Ellen W. Demerath, Kristin E. Anderson, Aaron R. Folsom, Corinne E. Joshu, Elizabeth A. Platz, Anna E. Prizment. Associations of leg length with increased colorectal cancer incidence in the atherosclerosis risk in communities (ARIC) study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4302.