BMI and waist circumference not only tell us something about fat mass, but are also predictors of an increased incidence of certain diseases such as cardiovascular disorders and cancer – as far as the medical consensus goes. A previously neglected parameter in risk research is body size. A publication from the Lancet Diabetes & Endocrinology comes up with an exciting “missing link” between the increase in body size over generations and the risk of cardiovascular disease and cancer.
First, some recent findings: According to the largest meta-analysis on the subject, with more than one million participants from 121 prospective studies, each 6.5 cm increase in height leads to a 4% increased risk of dying from cancer [1]. At the same time, however, the risk of death from cardiovascular disease decreases by 6%. Height was positively associated with melanoma mortality (26% increase per 6.5 cm increase), but also with pancreatic, endocrine, nervous, ovarian, breast, prostate, colorectal, blood, and lung tumors. The association was confirmed after controlling for important variables such as obesity, blood pressure, lipids, inflammatory markers, diabetes, or alcohol.
Cancer risk increases in taller people
Another prospective study with more than one million participants, the Million Women Study, reached a similar conclusion [2]. Increasing height by 10 cm increased the overall risk of developing cancer by 16%. The risk also increased for individual cancers:
- Colon cancer: 25%
- Rectal cancer: 14%
- Melanoma: 32%
- Breast and ovarian cancer: 17%
- Endometrial cancer: 19%
- Kidney cancer: 29%
- Non-Hodgkin’s lymphoma: 21%
- Leukemias: 26%
An additional meta-analysis showed that the same trend can be observed worldwide.
An analysis by the Women’s Health Initiative on a cohort of 144,701 postmenopausal women confirmed the positive association between body size and cancer risk [3]. Increasing length by 10 cm significantly increased overall cancer risk by 13% (range of 13% for breast cancer to 29% for multiple myeloma and thyroid cancer) – again after controlling for established risk factors.
Milk makes you perky – and big
Consequently, body size has an impact not only on the incidence but also on the mortality of certain common diseases, independent of BMI and other parameters. According to Prof. Dr. med. Norbert Stefan of the University Hospital Tübingen and his team, researching the relationship between body size and epidemiological, biological and pathophysiological factors in greater detail is all the more important because average height has been increasing in various countries for generations. This cannot be explained by genetic reasons alone.
It appears that insulin and insulin-like growth factor (IGF) signaling pathways play a critical role in both the increase in body size and the association between body size and cancer/cardiovascular disease. Overfeeding – especially of milk, dairy products, and other animal proteins – during pregnancy, early childhood, and puberty (i.e., growth phases) is likely to strongly activate these signaling pathways. Such activation of the IGF-1 and -2 systems could lead to a greater number of stem cells in the organs and thus to greater size growth. According to the authors, this can be seen in China, for example, where milk consumption and height growth among young people are increasing. In addition, Holland has at the same time the highest increase in average height and the highest per capita milk consumption.
Sustained cell growth promotion by an active IGF signaling pathway may also promote tumor cell growth. Perhaps avoiding such overeating could prevent accelerated growth in childhood and thus an increase in risk for cancer in adulthood.
And what about cardiovascular disease?
In addition to growth, IGF activation promotes insulin sensitivity and fat metabolism. New data show that taller people are more insulin sensitive and have lower fat content in the liver – a possible explanation for the lower risk of cardiovascular disease and type 2 diabetes.
Source: Stefan N, et al: Divergent associations of height with cardiometabolic disease and cancer: epidemiology, pathophysiology, and global implications. Lancet Diabetes & Endocrinology 2016 Jan. DOI: 10.1016/S2213-8587(15)00474-X [Epub ahead of print].
Literature:
- Emerging Risk Factors Collaboration: Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis. Int J Epidemiol 2012 Oct; 41(5): 1419-1433.
- 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 Aug; 12(8): 785-794.
- Kabat GC, et al: Adult Stature and Risk of Cancer at Different Anatomic Sites in a Cohort of Postmenopausal Women. Cancer Epidemiology, Biomarkers and Prevention 2013 Jul. DOI: 10.1158/1055-9965.EPI-13-0305.
InFo ONCOLOGY & HEMATOLOGY 2016; 4(2): 2
