Cancer risk is not (just) bad luck

TL;DR

This paper critiques the claim that random DNA replication errors are the main cause of cancer, emphasizing the significant roles of environmental and genetic factors in explaining variations in cancer risk across tissues.

Contribution

It challenges the previous conclusion by demonstrating that population heterogeneity and environmental/genetic influences are crucial in understanding cancer risk differences.

Findings

Large differences in cancer rates between organs exist.

Environmental and genetic factors significantly influence cancer risk.

Population heterogeneity affects correlation analyses.

Abstract

Tomasetti and Vogelstein recently proposed that the majority of variation in cancer risk among tissues is due to "bad luck," that is, random mutations arising during DNA replication in normal noncancerous stem cells. They generalize this finding to cancer overall, claiming that "the stochastic effects of DNA replication appear to be the major contributor to cancer in humans." We show that this conclusion results from a logical fallacy based on ignoring the influence of population heterogeneity in correlations exhibited at the level of the whole population. Because environmental and genetic factors cannot explain the huge differences in cancer rates between different organs, it is wrong to conclude that these factors play a minor role in cancer rates. In contrast, we show that one can indeed measure huge differences in cancer rates between different organs and, at the same time, observe a strong effect of environmental and genetic factors in cancer rates.