SCIENCE: Is getting breast cancer all down to (bad) luck?
Published 27 Mar 2017
A paper published last week in the journal Science has re-ignited the debate about whether the majority of cancers, including breast cancer, are simply down to bad luck.
The paper, by Tomasetti and co-workers from John Hopkins University, Baltimore, USA (1), is an expansion of a 2015 study (2) which used mathematical modelling to show that around two thirds of cancers are a result of random mutations that occur during DNA replication of adult stem cells, rather than mutations caused by environmental or hereditary factors. These random replication errors were described as “bad luck”, as they happen by chance and as such, are unpreventable.
Their current research considers the association between the number and rate of stem cell divisions and the risk of 17 cancer types, including breast cancer, using data from 69 countries.
Adult stem cells have the potential to divide, differentiate and replace dead or damaged cells. They occur in different organs in differing quantities. The more stem cell divisions, the more likely cancer will occur by random mutations.
The new data demonstrate a strong relationship between stem cell division and cancer type in all countries, but we question some of the assumptions made that led the authors to conclude that the vast majority of cancers, including breast cancer, are mostly unpreventable.
In their study, the authors estimate that 15% of breast cancer cases are associated with environmental factors, 5% genetics and the remaining 80% with random replication errors (“bad luck”). However, these figures are in contrast to most other studies which suggest that around 20-30% of breast cancers are familial (have an inherited component e.g. 3) and around 5% are associated with a single dominant gene mutation (such as BRCA1 or BRCA2 mutations). Although the estimates for the contribution of the environment to breast cancer vary, most studies estimate that around 30-50% have an environmental cause (e.g. 4, 5).
The research is based on a number of assumptions. One is that cancer is the result of an accumulation of mutations in dividing stem cells. Most researchers would agree that this is the basis of cancer, but it is generally accepted that cancer is more complex than this (6) and other factors, such as inflammation, immune responses, epigenetics and the tumour microenvironment play a role. The model also assumes that the number of stem cells in any particular tissue can be accurately estimated. But, in the case of breast tissue, estimates as to (for example) the proportion of stem cells present in breast tissue can vary over a 50 fold range (1), which calls into question the accuracy of some of the figures used for the analysis.
Breast Cancer UK believe that it is important to define accurately the percentage of cancers associated with the environment. Moreover, we believe that environmental factors do contribute significantly to breast cancer incidence and that contribution is far greater than the 15% estimated by Tomasetti and co-workers.
If most cancers were written off as “bad luck”, inevitably, more resources would be focused on early detection and treatments, to the detriment of preventative measures, reducing the number of cancers that might otherwise be prevented.
There is no doubt random mutations play an important role in all cancers. This has been known for many years; not everyone who smokes will get lung cancer and not everyone who has lung cancer has smoked. Similarly, not everyone who has a BRCA gene mutation will get breast cancer. And whilst we support efforts to improve early diagnoses, prevention is better than cure, and exaggerating the role of random mutations or “bad luck” will only diminish efforts to prevent cancer.
For further discussion surrounding this debate, please see our previous science comment on this topic.
1. Tomasetti, C. et al. (2017). Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science, 355 (6331): 1330-1334. http://science.sciencemag.org/content/355/6331/1330
2. Tomasetti, C. and Vogelstein, B. (2015). Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347 (6217): 78-81. https://www.ncbi.nlm.nih.gov/pubmed/25554788
3. Economopoulou, et al. (2015). Beyond BRCA: New hereditary breast cancer susceptibility genes. Cancer Treatment reviews 41: 1-8. http://www.sciencedirect.com/science/article/pii/S0305737214001741
4. Parkin, D. et al. (2011). The Fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. British Journal of Cancer 105, S77-s81. http://www.nature.com/bjc/journal/v105/n2s/full/bjc2011489a.html
5. Howell, A. et al. (2014). Risk determination and prevention of breast cancer. Breast Cancer Research 16(5): 446. https://www.ncbi.nlm.nih.gov/pubmed/25467785
6. Couzin-Frankel, J. (2017). Debate reignites over the contributions of ‘bad luck’ mutations to cancer. Science 355 (6331). http://www.sciencemag.org/news/2017/03/debate-reignites-over-contributions-bad-luck-mutations-cancer
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