Taller people have a greater chance of developing cancer than shorter people; however, the reason for this is unclear. As it has been observed that height increases the risk of a number of different types of cancers, a common mechanism might be at play.
It is likely that being tall is a marker for the “true” mechanism, rather than a causal factor. For example, taller people have more cells in their body and therefore may have a greater chance of developing cancerous cell changes.
It has also been suggested that early life nutrition and hormone levels related to growth could be responsible. Genome-wide association studies (GWAS) are used to identify common genetic factors that influence health and disease.
A recent meta-analysis of GWAS on height identified gene loci that cluster together in biologically relevant pathways. Intriguingly, several of these pathways have also been implicated in cancer development.
As the variation in adult height is determined by genetic and environmental interactions during the first 20 years of life, similar early life gene environment interactions may be related to cancer risk, thus explaining the observed non-causal link between height and cancer.
Aims and objectives
We aimed to investigate how energy restriction early in life influences colorectal, postmenopausal breast, and ovarian cancers through the pathways that also determine adult-attained height. This may lend support to the hypothesis that early life exposures play an important role in the association between height and cancer risk.
How the study was done
The unique Netherlands Cohort Study (NLCS) began in 1986 among 120,852 men and women aged 55–69 years who completed a self-administered questionnaire on dietary habits and other risk factors for cancer, including self-reported height and indicators of exposure to energy restriction during childhood and adolescence. Toenail clippings were collected at baseline and are available for DNA isolation and genotyping.
We used this data to assess whether energy restriction acts in conjunction with or through height when influencing cancer risk. Similarly, we investigated whether genetic variation relevant to growth affects the associations between energy restriction and height on the risk of cancer.
Conclusions
For every 5cm increase in height in adults, there was a 7% increased risk of postmenopausal breast cancer. This association was linked to hormone receptor-positive subtypes of breast cancer. In addition, height was associated with a 9% increased risk of colorectal cancer in women, but not in men. These observations may point to hormonal mechanisms underlying the associations between height and cancer.
Grant publications
- A systematic SNP selection approach to identify mechanisms underlying disease aetiology: linking height to postmenopausal breast and colorectal cancer risk
- Energy restriction at young age, genetic variants in the insulin-like growth factor pathway and colorectal cancer risk in the Netherlands Cohort Study
- A systematic literature review and meta-regression analysis on early-life energy restriction and cancer risk in humans
- Genetic variants in the insulin-like growth factor pathway and colorectal cancer risk in the Netherlands Cohort Study
