Comment www.thelancet.com/oncology Vol 12 August 2011 717 from childhood through to adulthood in the Boyd Orr cohort, 7 did not substantiate these findings. Green and colleagues 2 report a new effect modification: height-related relative risks were lower for smoking- related cancers than for other cancers, but these attenuated risks were restricted to present smokers. The authors reasoned that this interaction is probably additive and that pursuing it might identify new mechanisms. These findings are reminiscent of those between BMI and lung cancer, where incident cancer risk association with increasing BMI is paradoxically inverse, but when stratified by smoking status, this paradox is limited to current smokers. 8 For height-related cancer, smoking status might be a modifier, but socioeconomic class is probably an even greater source of confounding (figure). Increased BMI is an established risk factor for several cancer types, 8 but might be confounded by height. For example, BMI is inversely associated with premenopausal, but positively associated with postmenopausal, breast cancer risks. In the former setting, adult height is also a predictor of risk and might disproportionately influence the BMI ratio. Thus, short young women tend to be heavier, and, relative to tall thin women, might seem to have a lower risk of premenopausal breast cancer. BMI is a useful public health measure, but to address mechanistic questions, future studies should test additional readily derived indexes of adiposity such as the human body- shape index (weight in kg divided by height in m to the power of 2·76) and the ponderal index (weight in kg divided by the cube of height in m), which are less sensitive to height increments. In the future, researchers need to explore the predictive capacities of direct measures of nutrition, psychosocial stress, and illness during childhood, rather than final adult height. Extended follow-up of large childhood cohorts with longitudinal repeated exposure measurements are needed. 10 Assessing these cohorts will need new methods (eg, latent class analyses) 11 to tease out key factors that influence the subsequent development of height-related cancers. Andrew G Renehan School of Cancer and Enabling Sciences, University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UK arenehan@picr.man.ac.uk I have served on the advisory board of and received research support from Novo Nordisk. 1 World Cancer Research Fund, American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington, DC: AICR, 2007. 2 Green J, Cairns BJ, Casabonne D, Wright FL, Reeves G, Beral V. 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; published online July 21. DOI:10.1016/S1470-2045(11)70154-1. 3 Elias SG, Peeters PH, Grobbee DE, van Noord PA. The 1944–1945 Dutch famine and subsequent overall cancer incidence. Cancer Epidemiol Biomarkers Prev 2005; 14: 1981–85. 4 Ahlgren M, Melbye M, Wohlfahrt J, Sorensen TI. Growth patterns and the risk of breast cancer in women. N Engl J Med 2004; 351: 1619–26. 5 Clayton PE, Banerjee I, Murray PG, Renehan AG. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol 2011; 7: 11–24. 6 Lawlor DA, Okasha M, Gunnell D, Smith GD, Ebrahim S. Associations of adult measures of childhood growth with breast cancer: findings from the British Women’s Heart and Health Study. Br J Cancer 2003; 89: 81–87. 7 Whitley E, Martin RM, Smith GD, Holly JM, Gunnell D. Childhood stature and adult cancer risk: the Boyd Orr cohort. Cancer Causes Control 2009; 20: 243–51. 8 Renehan A, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371: 569–78. 9 NHS. Health Survey for England. http://www.ic.nhs.uk/statistics-and-data- collections/health-and-lifestyles-related-surveys/health-survey-for-england (individual personal data accessed under licence via http://www.methodbox. org on July 3, 2011). 10 Batty GD, Shipley MJ, Gunnell D, et al. Height, wealth, and health: an overview with new data from three longitudinal studies. Econ Hum Biol 2009; 7: 137–52. 11 Henderson J, Granell R, Heron J, et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax 2008; 63: 974–80. In this issue of The Lancet Oncology, Kenneth O’Byrne and colleagues 1 report an analysis of potential biomarkers from a phase 3 trial of cisplatin and vinorelbine with and without cetuximab, an EGFR monoclonal antibody, in patients with advanced non- small-cell lung cancer (NSCLC). In 2009, KRAS codon 12 and 13 mutational status was recorded to be predictive of benefit of the anti-EGFR monoclonal antibodies cetuximab and panitumumab in advanced colorectal cancer (CRC). 2 The benefit of these agents was thought to be restricted to the subset of patients with KRAS wild-type tumours; consequently only patients with KRAS wild-type tumours receive these agents. 3 However, findings from subsequent exploratory analyses of KRAS G13D compared with other KRAS mutations in metastatic CRC showed that tumours with KRAS G13D mutations had a better prognosis and a better outcome after treatment with cetuximab than Are all KRAS mutations created equal? Published Online July 21, 2011 DOI:10.1016/S1470- 2045(11)70200-5 See Articles page 795