Leg length and risk of cancer in the Boyd Orr cohortBMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7169.1350 (Published 14 November 1998) Cite this as: BMJ 1998;317:1350
- D J Gunnell, senior lecturer in epidemiology and public health medicine ()a,
- G Davey Smith, professor of clinical epidemiologya,
- J M P Holly, professor of clinical sciencesb,
- S Frankel, professor of epidemiology and public health medicinea
- aDepartment of Social Medicine Canynge Hall, Bristol BS8 2PR
- bDivision of Surgery University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW
- Correspondence to Dr Gunnell
- Accepted 28 July 1998
Editorial by Albanes
Height is directly associated with mortality from cancer,1 but the explanation for this association is unclear. Whereas adult height is a marker of nutrition and health throughout childhood, most growth before puberty is due to increases in leg length. Leg length can therefore be used as a marker for exposures that generate the association between adult height and cancer. 1 2 We examined the association between prepubertal leg length and mortality from cancer in the Boyd Orr cohort. 2 3
Subjects, methods, and results
As childhood height is affected by the timing of puberty we restricted our analysis to study members who were aged 2-8 years when their height and leg length were measured. In all, 1167 of these 1392 subjects (84%) were traced and had information on childhood and adult socioeconomic status, and they form the basis of this analysis. Using Cox's proportional hazards models we examined mortality from cancer between 1948 and 1997 in relation to internally derived z scores for childhood leg length.2 All traced subjects were included in these models up to the time of their death or emigration. To adjust for possible genetic factors associated with overall stature all models also include a term for trunk length z score. The z score (standard deviation score) expresses a child's measurement as the number of standard deviations its value is from the mean for its age and sex. In these analyses each unit of the z score is approximately equivalent to 3-4 mm (the standard deviation for leg length in these children).
We classed cancers as related to smoking (codes 140, 141, 143-9, 150, 157, 160-3, 188-9 of the international classification of diseases, ninth revision (ICD-9)) and not related to smoking (all other malignant neoplasms, but mainly colorectal, breast, and ovarian cancers). We further divided cancers unrelated to smoking into sex hormone dependent (174 (breast), 179 (uterus), 182-7 (ovary, prostate, and other genital organs)) and non-sex hormone dependent (all other cancers unrelated to smoking).
The analysis showed a significant positive association between childhood leg length and mortality from cancers unrelated to smoking (table). The observed association was most obvious for mortality from sex hormone dependent cancers—the risk of death increased by 129% (95% confidence interval 9% to 383%) for every unit increase in z score for leg length. No significant associations were seen in relation to trunk length (hazard ratio for cancers unrelated to smoking 0.84 (0.58 to 1.22)), and the associations for overall height were in a similar direction but weaker than those for leg length. There was no association with all cause mortality.
In the literature associations between height and cancer have been most consistently shown for breast and prostate cancer, both of which may be hormonally dependent. In line with this, the associations reported here are strongest in relation to sex hormone dependent cancers. Two possible mechanisms may underlie these associations. Firstly, more rapid growth is associated with an earlier puberty and therefore a longer exposure to adult concentrations of sex hormones. Secondly, childhood diet may influence concentrations of insulin-like growth factor-I,4 subsequent growth (as indexed by childhood leg length),2 and later risk of cancer.3 Insulin-like growth factor-I may increase the risk of cancer through several mechanisms, including protecting genetically damaged cells from apoptosis (cell suicide), stimulating cell proliferation, and amplifying the production of sex hormones by gonadotrophins.4 A role of insulin-like growth factor-I in cancer development is further supported by the results of recent prospective studies showing its strong association with risk of breast and prostate cancer. 4 5 In one study the associations were independent of sex hormone concentrations.5 Future studies should determine whether growth hormones are as important in the aetiology of human cancer as they are in animal experiments.
We thank Professor Philip James, director of the Rowett Research Institute, for the use of the archive and in particular Walter Duncan, honorary archivist to the institute, for his help. We also thank the staff at the NHS Central Register at Southport and Edinburgh; Sara Bright, Sue Williams, Andrea Wilson, Jenny Eachus, and Sarah Pike for data entry; Tim Peters, Fiona Braddon, Sara Brookes, Phil Chan, and Martin Kemp for technical help; and Dr David Smith for helping us to contact surviving members of the survey teams and for access to his interviews with some of these people. We also acknowledge all the research workers and subjects who participated in the original survey in 1937-9. In particular, we thank Professor J Pemberton, Mrs I Crichton, and the late David Lubbock for information on the design and conduct of the original survey.
Contributors: The Boyd Orr cohort was established by GDS and SF. DJG further developed and refined the cohort. GDS and DJG initiated this reanalysis, and the analyses presented here were performed by DJG. JMPH provided input on the possible role of growth factors in the observed associations. DJG wrote the first draft of the paper and GDS, SF, and JMPH all commented and helped in redrafting the text. DJG, GDS, and SF are guarantors for the study.
Funding Research on the Boyd Orr cohort was funded by the World Cancer Research Fund, British Heart Foundation, and the Medical Research Council
Conflict of interest None.