Size matters: height, cell number and a person's risk of cancer.

摘要: The multistage model of carcinogenesis predicts cancer risk will increase with tissue size, since more cells provide targets for oncogenic somatic mutation. However, this is not seen among mammal species different sizes (Peto's paradox), a paradox argued to be due larger evolving added suppression. If explanation correct, the cell number effect still expected within species. Consistent this, hazard ratio overall per 10 cm in human height (HR10) about 1.1, indicating 10% cm; however, an alternative invokes indirect height, factors that independently increasing adult height. data from four large-scale surveillance projects on 23 categories were tested against quantitative predictions cell-number hypothesis, accurately supported. For HR10 predicted versus observed was 1.13 1.12 women and 1.11 1.09 men, suggesting variation provides null hypothesis assessing effects. Melanoma showed unexpectedly strong relationship additional effect, perhaps division rate mediated through IGF-I Similarly, only one-third higher incidence non-reproductive cancers men can explained by number. risks obesity are correlated effects consistent primary causation. direct suggests caution identifying height-related SNPs as causing.