Height, birthweight and cancer risk - exposures reportA baby’s size and shape at birth depends on how well they grow in the womb. Within the usual range, heavier (and longer) babies tend to become taller children and adults.

Final adult height is linked to genetics, birthweight, rate of growth and age of puberty, as well as environmental factors that include nutrition. Periods of peak growth (such as in infancy and adolescence) are especially important in determining height, because growth is particularly sensitive to nutritional supply during these times. Growth is also especially dependent on the action of growth hormones and growth factors.

A baby’s birthweight and an adult’s height therefore both reflect a complex interplay of genetic, nutritional and other environmental factors that affect growth within the womb and during childhood and adolescence. Birthweight and height are markers of these factors. Neither birthweight nor height is likely to affect the risk of cancer directly.

Our major findings on this exposure

There is strong evidence that:

  • developmental factors leading to greater growth in length in childhood (marked by adult attained height) INCREASE the risk of cancers of the following types: pancreas, colorectum, breast (pre and postmenopause), ovary, endometrium, prostate, kidney and skin (malignant melanoma)
  • factors that lead to a greater birthweight, or its consequences, INCREASE the risk of premenopausal breast cancer

The evidence shows that, in general, the taller people are during adulthood and the more people weighed at birth, the higher their risk of some cancers.

height and birthweight and cancer matrix

See more graphics in our toolkit.

Recommendations

Although adult attained height and birthweight are public health issues, as adults, people cannot modify these factors. It is therefore inappropriate to make a global recommendation on height.

Birth to death

A baby’s size and shape at birth are an indication of the extent and quality of intra-uterine growth and development. Birthweight can be measured simply and reliably, whereas head circumference, which marks growth of the brain, and head-to-foot length, which marks linear growth, are more difficult to measure reliably. Within the usual range, heavier (and longer) babies tend to become taller children and adults.

Birthweight can predict the risk of death and of various diseases in infancy and later in life. Very low birthweight – less than 2.5 kilograms (5.5 lbs) for boys and 2.4 kilograms (5.3 lbs) for girls – increases the risk of perinatal death and disease, or death in infancy and young childhood, usually because of increased vulnerability to infection.

It is well established, at least in high-income countries, that there is a graded relationship, throughout the normal range, between size at birth, and at one year of age, and risk of chronic disease such as cardiovascular disease and type 2 diabetes during adult life, such that lower weight predicts higher risk.

Very high birthweight may also be associated with increased risk of certain diseases – for instance, maternal diabetes or poor glucose homeostasis can cause higher birthweight as well as increased risk of diabetes in the infant. These findings have been shown to be independent of smoking tobacco or socioeconomic status, although they may be accentuated in the presence of these additional stress factors.

Mechanisms

Adult attained height and colorectal cancer

The proposed mechanisms by which adult attained height is linked to risk of colorectal cancer include greater exposure to growth factors such as growth hormone and insulin-like growth factors (IGFs) in childhood and early adulthood and excess calorie consumption in early life. Taller people have more cells and thus there is greater opportunity for mutations leading to cancer development. In addition, taller adults also have longer intestines; therefore, there may be greater potential for DNA damage resulting from exposure to mutagenic or cancer-promoting agents. Overall there are moderate mechanistic data supporting greater adult height as a risk factor for colorectal cancer.

Adult attained height and breast cancer

Adult height is directly related to the rate of growth during fetal life and childhood. The number of cell divisions in fetal life and childhood and age of sexual maturity are all determined by the hormonal microenvironment (circulating plasma levels of growth factors and oestrogens and their respective binding proteins), which is influenced by nutritional status.

Many of these mechanisms, such as early-life nutrition affecting body composition and altered circulating and hormone profiles, can modulate the rate of tissue growth and sexual maturation. It is therefore plausible that nutritional factors during childhood and adolescence that affect height could also influence cancer risk. Specific tissues in taller people are exposed to higher levels of insulin, pituitary-derived growth hormone and IGFs, and thus may have undergone more cell divisions. This increased number of cell divisions may contribute to greater potential for error during DNA replication, resulting in an increased risk of developing cancer. Therefore, adult attained height may be a marker of inherited factors as well as fetal and childhood experience and is also a surrogate for important nutritional exposures, which affect several hormonal and metabolic axes and which may influence breast cancer risk.

Adult attained height and ovarian cancer

Adult height is determined by inherited genetic factors as well as through specific exposures, such as nutrition and infections in utero, as well as throughout childhood and adolescence. These factors may also affect ovarian cancer risk later in life through alterations in hormonal pathways, in particular the IGF-I pathway. However, results from epidemiological studies on circulating IGF-I levels and ovarian cancer risk have been inconclusive.

Adult attained height and pancreatic cancer

Specific mechanisms that link greater adult height with an increased risk of pancreatic cancer have not been clearly identified but may include those that have been proposed for other height-related cancers. Greater adult height may be related to increased exposure to endocrine and metabolic patterns, such as IGFs, in childhood and early adulthood, which have been associated with organ growth, greater cell division, and thus risk of cancer-initiating mutations. In addition, taller people have more cells and thus there is greater opportunity for mutations to arise and lead to cancer development.

Adult attained height and endometrial cancer

Adult height is directly related to the rate of growth during fetal life and childhood. The number of cell divisions in fetal life and childhood, health and nutrition status in childhood, and age of sexual maturity are all determined by the hormonal microenvironment (plasma levels of growth factors and oestrogens and their respective binding protein), which is influenced by nutritional status. Many of these mechanisms, such as early-life nutrition affecting body composition and altered circulating and free hormone profiles, can modulate the rate of tissue growth and sexual maturation. It is therefore plausible that nutritional factors that affect height could also influence cancer risk. Specific tissues in taller people are exposed to higher levels of insulin, pituitary-derived growth hormone and IGFs, and thus may have undergone more cell divisions. This increased number of cell divisions may contribute to greater potential for error during DNA replication, resulting in an increased risk of developing cancer. Therefore, adult attained height is a marker of inherited factors as well as fetal and childhood experience and is also a surrogate for important nutritional exposures, which affect several hormonal and metabolic axes and which may influence endometrial cancer risk.

Adult attained height and prostate cancer

Greater adult attained height is associated with higher risk of prostate cancer; however, specific mechanisms that link greater adult height with higher risk of prostate cancer have not been identified. Adult height may be viewed as a marker of factors affecting linear growth including nutritional and genetic factors as well as cumulative exposure to endogenous hormones such as growth hormone and IGFs. The IGF axis plays a major role in the regulation of cell growth and survival, and experimental studies demonstrate that increased signalling through the IGF-system can exert a pro-tumorigenic effect. Recently, a large-scale collaborative meta-analysis of studies examining the relation between circulating IGF-I and the incidence of prostate cancer reported a robust, positive association between IGF-I levels and prostate cancer risk. Therefore, the IGF-axis may represent a plausible mechanism linking height to prostate cancer development. An additional proposed mechanism relates to taller people having more cells and thus there is greater opportunity for mutations to arise and lead to cancer development.

Adult attained height and kidney cancer

Specific mechanisms that link greater adult height with an increased risk of kidney cancer have not been clearly identified but may include those that have been proposed for other height-related cancers. Greater adult height may be related to increased exposure to endocrine and metabolic patterns, such as IGFs, in childhood and early adulthood, which have been associated with organ growth, greater cell division, and thus risk of cancer-initiating mutations. In addition, taller people have more cells and thus there is greater opportunity for mutations to arise and lead to cancer development.

Adult attained height and skin cancer

The mechanisms by which higher adult attained height is linked to elevated risks of malignant melanoma and basal cell carcinoma are unclear. Taller people have more skin cells, and thus there is greater opportunity for mutations leading to cancer development. In addition, early life and early adulthood exposures may play a role, such as greater exposure to growth factors, including growth hormone and IGFs, and excess calorie consumption in early life.

Greater birthweight and breast cancer (premenopausal)

There are many general mechanisms, such as long-term programming of hormonal systems, which could possibly increase cancer risk and can be marked by variation in birthweight. Greater birthweight is associated with higher circulating maternal oestrogen levels and may increase IGF-1 activity; low birthweight raises fetal and maternal levels of IGF-1 binding protein. The action of both oestrogens and IGF-1 are thought to be important in fetal growth and very early fetal mammary gland development and play a role in the initiation and promotion of breast cancer. Animal experiments also provide evidence that exposure to oestrogens during fetal and early postnatal development can increase the risk of mammary cancers.

Greater birthweight and skin cancer

Birthweight is a marker of certain aspects of the general fetal growth environment that may influence the development of cancer at later life, through largely uncharacterised biological pathways. Proposed mechanisms include larger infants having a greater number of susceptible cells and in utero programming of IGFs such as IGF-1, which may lead to greater postnatal cellular proliferation.

This webpage is a summary.

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