Height and Cancer Risk

Abstract & Commentary

By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC. Dr. Ershler reports no financial relationships relevant to this field of study.

This article originally appeared in the November issue of Clinical Oncology Alert. At that time it was peer reviewed by V.R. Veerapalli, MD, Staff Clinician, INOVA Fairfax Cancer Center, Falls Church, VA. Dr. Veerapalli reports no financial relationships relevant to this field of study.

Synopsis: From a large cohort of women followed prospectively and with an adjunct meta-analysis of existing evaluable studies, a clearly demonstrated, nearly universal (i.e., across tumor types) incremental increase in cancer incidence was observed with advancing height.

Source: Green J, et al. Height and cancer incidence in the Million Women Study: Prospective cohort, and meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol 2011;12:785-794.

A number of epidemiological studies have demonstrated an increased risk of cancer in taller people, but it remains unclear if this height-associated risk is cancer-type specific and if it can be accounted for by confounding factors such as socioeconomic status or cigarette smoking. The goal of the current analysis was to investigate these associations in a large UK prospective cohort with sufficient information on incident cancer to allow direct comparison of height-associated risk across cancer sites and in relation to major potential confounding and modifying factors.

Between 1996 and 2001, 1.3 million middle-aged women with no known prior cancer were enrolled in the UK National Health Service Breast Screening Program (Million Women Study). One aspect of this comprehensive research program was the completion of a recruitment questionnaire that probed characteristics including current height, weight, smoking history, and other social, demographic, and lifestyle factors. A small subset of respondents (n = 3762) were invited to have their height/weight measured at their family physician’s office, and these measures correlated remarkably well to earlier self-reports, allowing confidence that the self-reports were valid measures for the population as a whole.

There were 1.3 million women enrolled and followed for a median of 9.4 years (11.7 million person years). During this time, 97,376 new cases of cancer (all sites, other than non-melanoma skin) were diagnosed. The investigators used Cox regression models to calculate adjusted relative risks (RR) per 10 cm increase in measured height for total and site-specific incident cancers, taking attained age as the underlying time variable.

The RR for total cancer was of 1.16 (95% confidence interval [CI] 1.14-1.17; P < 0.0001) for every 10 cm increase in height. Risk increased for 15 of the 17 assessed cancer sites and was statistically significant for 10 sites: colon, rectum, malignant melanoma, breast, endometrium, ovary, kidney, central nervous system, non-Hodgkin’s lymphoma, and leukemia. The increase in total cancer RR per 10 cm increase in height did not vary significantly by socioeconomic status or by 10 other personal characteristics, but was significantly lower in current than in never smokers (P < 0.0001). In current smokers, smoking-related cancers were not as strongly related to height as were other cancers. The investigators also performed a meta-analysis including their findings with 10 other prospective studies, and this demonstrated the height-associated RRs for total cancer varied little across Europe, North America, Australia, and Asia.

Commentary

The current report confirms findings from several smaller studies that cancer incidence increases with increasing adult height.1-5 Furthermore, because of its large size and careful analysis, it also demonstrated that the height-associated increased risk was relevant to most of the common cancer types, and was apparent even when confounding factors such as socioeconomic status, cigarette smoking, alcohol use, body mass index, age at menarche, parity, and age at first birth were accounted for. Furthermore, combining these data with other published reports in meta-analysis, the relationship of height and total cancer RR is similar in different populations and in both men and women.

The findings are hypothesis-generating, as there is no clear explanation. Earlier reports that were not quite as robust left the impression that the increased height-associated risk of cancer could be explained by socioeconomic factors or cigarettes.6,7 Supporting this, the current analysis demonstrated that taller women tend to have higher socioeconomic status, drink more alcohol, be more active, exercise more, smoke less, have later menarche, have fewer children, and give birth later in life â€" all factors that might influence cancer incidence. Yet, when the data were adjusted for each of these factors (and others) the height-associated risk remained significant. Furthermore, the association is observable for 15 of the 17 most common cancer sites, suggesting a more fundamental mechanism. Identifying this mechanism might provide greater insight into cancer susceptibility. Perhaps it is nothing more than tall people carry a larger cellular load and a correspondingly larger number of targets for cancer development, although this explanation seems unlikely. Another possibility is that growth promoting factors accounting for increased body stature during development may have residual biological activity upon maturity. Of course, these are conjectural but investigations along those lines would be a logical translation of this interesting and important epidemiological study.

References

1. Albanes D, et al. Adult stature and risk of cancer. Cancer Res 1988;48:1658-1662.

2. Batty GD, et al. Adult height in relation to mortality from 14 cancer sites in men in London (UK): Evidence from the original Whitehall study. Ann Oncol 2006;17:157-166.

3. Gunnell D, et al. Height, leg length, and cancer risk: A systematic review. Epidemiol Rev 2001;23:313-342.

4. Olsen CM, et al. Anthropometric factors and risk of melanoma in women: A pooled analysis. Int J Cancer 2008;122:1100-1108.

5. Pischon T, et al. Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2006;98:920-931.

6. Batty GD, et al. Height, wealth, and health: An overview with new data from three longitudinal studies. Econ Hum Biol 2009;7:137-152.

7. Sung J, et al. Height and site-specific cancer risk: A cohort study of a korean adult population. Am J Epidemiol 2009;170:53-64.