Musings on the theory that variation in cancer risk among tissues can be explained by the number of divisions of normal stem cells

TL;DR

This paper discusses the hypothesis that differences in cancer risk among tissues are primarily due to the number of normal stem cell divisions, addressing statistical and technical issues from a previous study.

Contribution

It clarifies and responds to critiques of their 2015 study, reinforcing the role of stem cell divisions in explaining tissue-specific cancer risks.

Findings

Stem cell divisions correlate with tissue-specific cancer risk

Random mutations from stem cell divisions significantly influence cancer incidence

Addressed statistical and technical concerns from prior analysis

Abstract

This manuscript has been written to address questions related to our recent publication (Science 347:78-81, 2015). We appreciate the many reactions to this paper that have been communicated to us, either privately or publicly. The following addresses several of the most important statistical and technical issues related to our analysis and conclusions. Our responses to non-technical questions are available at http://www.hopkinsmedicine.org/news/media/releases/bad_luck_of_random_mutations_plays_predominant_role_in_cancer_study_shows