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Substantial contribution of extrinsic risk factors to cancer development.

Wu S, Powers S, Zhu W, Hannun YA - Nature (2015)

Bottom Line: Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks.Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors.These results are important for strategizing cancer prevention, research and public health.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794, USA.

ABSTRACT
Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the 'bad luck' hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (less than ~10-30% of lifetime risk) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. We then show that intrinsic risk is better estimated by the lower bound risk controlling for total stem-cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health.

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Examples of increased cancer incidence trends from 1973 – 2012The cancer types include cervix uteri cancer, gallbladder cancer, esophagus cancer, melanoma, thyroid cancer, kidney cancer, liver cancer, small intestine cancer, thymus cancer, anal and anorectal cancer. The horizontal dashed line indicates the historical minimal incidence. The vertical solid line indicates the most recent year. The number represents the minimal percentage of extrinsic risk. The incidence rate is based on per 100,000 people.
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Figure 5: Examples of increased cancer incidence trends from 1973 – 2012The cancer types include cervix uteri cancer, gallbladder cancer, esophagus cancer, melanoma, thyroid cancer, kidney cancer, liver cancer, small intestine cancer, thymus cancer, anal and anorectal cancer. The horizontal dashed line indicates the historical minimal incidence. The vertical solid line indicates the most recent year. The number represents the minimal percentage of extrinsic risk. The incidence rate is based on per 100,000 people.

Mentions: Additionally, analyses of data from the Surveillance, Epidemiology, and End Results Program (SEER) in U.S. between 1973–2012 demonstrate that while many cancers maintain relatively consistent age-adjusted incidence rates, e.g. esophagus cancer, incidences for some cancers, including melanoma, thyroid, kidney, liver, thymus, small intestine, extranodal non-Hodgkin’s lymphoma (NHL), testis, anal and anorectal cancers, have been steadily increasing and their current incidences are substantially higher than their historical minima in the past 40 years28 (Extended Data Fig. 1). Moreover, the mortality trend of lung cancer from 1930–201129, which usually mirrors its incidence trend, shows more than 15-fold increase for lung cancer risk. These significant increases in incidence suggest that substantial risk proportions are attributable to changing environments (e.g. smoking and air pollutants to lung cancers). Collectively, nearly all major cancers have been covered in these epidemiological studies, further supporting the hypothesis of substantial extrinsic risks for most cancers. Remarkably, it should be noted that most of these cancers from the epidemiological and SEER results, except for small intestine (which starts from a very low risk although it is increasing), are located above the red “intrinsic” risk lines in Figs. 3a & 3b (blue points), and accounting for the external factors would move them closer to the proposed ‘intrinsic’ line; thus further supporting the conjecture that the intrinsic line is mainly defined by cancers without compelling known epidemiological risk whereas those above are at higher risks due to extrinsic factors.


Substantial contribution of extrinsic risk factors to cancer development.

Wu S, Powers S, Zhu W, Hannun YA - Nature (2015)

Examples of increased cancer incidence trends from 1973 – 2012The cancer types include cervix uteri cancer, gallbladder cancer, esophagus cancer, melanoma, thyroid cancer, kidney cancer, liver cancer, small intestine cancer, thymus cancer, anal and anorectal cancer. The horizontal dashed line indicates the historical minimal incidence. The vertical solid line indicates the most recent year. The number represents the minimal percentage of extrinsic risk. The incidence rate is based on per 100,000 people.
© Copyright Policy - permissions-link
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4836858&req=5

Figure 5: Examples of increased cancer incidence trends from 1973 – 2012The cancer types include cervix uteri cancer, gallbladder cancer, esophagus cancer, melanoma, thyroid cancer, kidney cancer, liver cancer, small intestine cancer, thymus cancer, anal and anorectal cancer. The horizontal dashed line indicates the historical minimal incidence. The vertical solid line indicates the most recent year. The number represents the minimal percentage of extrinsic risk. The incidence rate is based on per 100,000 people.
Mentions: Additionally, analyses of data from the Surveillance, Epidemiology, and End Results Program (SEER) in U.S. between 1973–2012 demonstrate that while many cancers maintain relatively consistent age-adjusted incidence rates, e.g. esophagus cancer, incidences for some cancers, including melanoma, thyroid, kidney, liver, thymus, small intestine, extranodal non-Hodgkin’s lymphoma (NHL), testis, anal and anorectal cancers, have been steadily increasing and their current incidences are substantially higher than their historical minima in the past 40 years28 (Extended Data Fig. 1). Moreover, the mortality trend of lung cancer from 1930–201129, which usually mirrors its incidence trend, shows more than 15-fold increase for lung cancer risk. These significant increases in incidence suggest that substantial risk proportions are attributable to changing environments (e.g. smoking and air pollutants to lung cancers). Collectively, nearly all major cancers have been covered in these epidemiological studies, further supporting the hypothesis of substantial extrinsic risks for most cancers. Remarkably, it should be noted that most of these cancers from the epidemiological and SEER results, except for small intestine (which starts from a very low risk although it is increasing), are located above the red “intrinsic” risk lines in Figs. 3a & 3b (blue points), and accounting for the external factors would move them closer to the proposed ‘intrinsic’ line; thus further supporting the conjecture that the intrinsic line is mainly defined by cancers without compelling known epidemiological risk whereas those above are at higher risks due to extrinsic factors.

Bottom Line: Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks.Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors.These results are important for strategizing cancer prevention, research and public health.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794, USA.

ABSTRACT
Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the 'bad luck' hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (less than ~10-30% of lifetime risk) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. We then show that intrinsic risk is better estimated by the lower bound risk controlling for total stem-cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health.

Show MeSH
Related in: MedlinePlus