Anthropogenic risk factors as the major cause of cancer driver events

Mapping Intimacies ◽

10.1101/486860 ◽

2018 ◽

Author(s):

Aleksey V. Belikov

Keyword(s):

Risk Factors ◽

Probability Distribution ◽

Cancer Incidence ◽

Risk Estimation ◽

Age Distribution ◽

Erlang Distribution ◽

Modifiable Risk Factors ◽

Cancer Driver ◽

Replication Errors ◽

Rate Limiting

AbstractBackgroundI have recently shown that the number of rate-limiting driver events per tumor can be estimated from the age distribution of cancer incidence using the gamma/Erlang probability distribution. It is important to understand how these predictions relate to established risk factors.MethodsThe number of rate-limiting driver events per tumor was estimated using the gamma/Erlang distribution and correlated to the percentage of cancer cases attributable to modifiable risk factors.ResultsThe predicted number of rate-limiting driver events per tumor strongly correlates with the proportion of cancer cases attributable to modifiable risk factors for all cancers except those induced by infection or ultraviolet radiation. The correlation was confirmed for three countries, three corresponding incidence databases and risk estimation studies, as well as for both sexes: USA, males [r=0.80, P=0.002], females [r=0.81, P=0.0003]; England, males [r=0.90, P<0.0001], females [r=0.67, P=0.002]; Australia, males [r=0.90, P=0.0004], females [r=0.68, P=0.01].ConclusionsIt is thus confirmed that predictions based on interpreting the age distribution of cancer incidence as the gamma/Erlang probability distribution have biological meaning, validating the underlying Poisson process as the law governing the development of the majority of cancer types, especially those driven by chemical mutagens. Importantly, this study suggests that the majority of driver events (60-80% in males, 50-70% in females) are induced by anthropogenic carcinogens, and not by cell replication errors or other internal processes.

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Cancer types with high numbers of driver events are largely preventable

PeerJ ◽

10.7717/peerj.12672 ◽

2022 ◽

Vol 10 ◽

pp. e12672

Author(s):

Aleksey V. Belikov ◽

Sergey V. Leonov

Keyword(s):

Risk Factors ◽

Probability Distribution ◽

Cancer Incidence ◽

Risk Estimation ◽

Age Distribution ◽

Modifiable Risk Factors ◽

Cancer Type ◽

Cancer Types ◽

Extrinsic Risk ◽

Rate Limiting

There is a long-standing debate on whether cancer is predominantly driven by extrinsic risk factors such as smoking, or by intrinsic processes such as errors in DNA replication. We have previously shown that the number of rate-limiting driver events per tumor can be estimated from the age distribution of cancer incidence using the gamma/Erlang probability distribution. Here, we show that this number strongly correlates with the proportion of cancer cases attributable to modifiable risk factors for all cancer types except the ones inducible by infection or ultraviolet radiation. The correlation was confirmed for three countries, three corresponding incidence databases and risk estimation studies, as well as for both sexes: USA, males (r = 0.80, P = 0.002), females (r = 0.81, P = 0.0003); England, males (r = 0.90, P < 0.0001), females (r = 0.67, P = 0.002); Australia, males (r = 0.90, P = 0.0004), females (r = 0.68, P = 0.01). Hence, this study suggests that the more driver events a cancer type requires, the more of its cases are due to preventable anthropogenic risk factors.

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WCRF/AICR recommendation adherence and breast cancer incidence among postmenopausal women with and without non-modifiable risk factors

International Journal of Cancer ◽

10.1002/ijc.29994 ◽

2016 ◽

Vol 138 (11) ◽

pp. 2602-2615 ◽

Cited By ~ 36

Author(s):

Sarah J.O. Nomura ◽

Maki Inoue-Choi ◽

DeAnn Lazovich ◽

Kim Robien

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Postmenopausal Women ◽

Cancer Incidence ◽

Breast Cancer Incidence ◽

Modifiable Risk Factors ◽

Recommendation Adherence

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Attributable Causes of Cancer in Vietnam

JCO Global Oncology ◽

10.1200/jgo.19.00239 ◽

2020 ◽

pp. 195-204

Author(s):

Thuy Phuong Nguyen ◽

Hung N. Luu ◽

Mai Vu Tuyet Nguyen ◽

Mo Thi Tran ◽

Thuy Thi Van Tuong ◽

...

Keyword(s):

Risk Factors ◽

Cancer Incidence ◽

Tobacco Smoking ◽

Alcohol Drinking ◽

Economic Transition ◽

Cancer Registries ◽

Modifiable Risk Factors ◽

Chronic Infections ◽

Cancer Burden ◽

Fundamental Research

PURPOSE Vietnam is undergoing rapid socio-economic transition with an increasing cancer burden. The contribution of modifiable risk factors to cancers in Vietnam has not been studied. Therefore, we sought to evaluate the attributable causes of cancer in Vietnam. METHODS We reviewed the data on burden of cancer in Vietnam from 2 cancer registries in Hanoi and Ho Chi Minh City between 1995 and 2012. Next, we calculated the fractions of cancers occurring in 2018 attributable to established modifiable risk factors whose impact could be quantified. Data on exposure prevalence were obtained for the period from 2000 to 2010 from national sources wherever possible. RESULTS Cancer incidence in Vietnam has decreased slightly in both sexes. Cancer related to infectious agents decreased sharply, whereas cancer related to nutrition and metabolism has increased. In 2018, established carcinogens included in the analysis explained 47.0% of cancer burden in Vietnam. Chronic infections accounted for 29.1% of cancers (34.7% in men and 22.1% in women), tobacco smoking for 13.5% (23.9% in men and 0.8% in women), and alcohol drinking for 10.3%. Passive smoking was responsible for 8.8% of cancers in women. Other risk factors, including overweight or obesity, nulliparity, and low vegetable and fruit intake, accounted for < 1% of all cancers each. CONCLUSION Cancer incidence is slowly decreasing in Vietnam, and the causes of more than half of cancers remain unexplained. This result underlines the need for further epidemiologic and fundamental research. Our findings confirm the notion that controlling oncogenic infections and decreasing tobacco smoking are the most effective approaches to reduce the burden of cancer in Vietnam, but other risk factors, including alcohol drinking and diet, should not be neglected.

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Abstract 146: WCRF/AICR recommendation adherence and breast cancer incidence among postmenopausal women with non-modifiable risk factors.

10.1158/1538-7445.am2013-146 ◽

2013 ◽

Author(s):

Sarah Oppeneer ◽

Maki Inoue-Choi ◽

DeAnn Lazovich ◽

Kim Robien

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Postmenopausal Women ◽

Cancer Incidence ◽

Breast Cancer Incidence ◽

Modifiable Risk Factors ◽

Recommendation Adherence

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The Poisson process is the universal law of cancer development: driver mutations accumulate randomly, silently, at constant average rate and for many decades, likely in stem cells

10.1101/231027 ◽

2017 ◽

Cited By ~ 1

Author(s):

Aleksey V. Belikov ◽

Alexey D. Vyatkin ◽

Sergey V. Leonov

Keyword(s):

Stem Cells ◽

Probability Distribution ◽

Poisson Process ◽

Old Age ◽

Average Rate ◽

Age Distribution ◽

Cancer Development ◽

Driver Mutations ◽

Erlang Distribution ◽

Universal Law

AbstractBackgroundIt is assumed that cancers develop upon acquiring a particular number of (epi)mutations in driver genes, but the law governing the kinetics of this process is not known. We have recently shown that the age distribution of incidence for 20 most prevalent cancers of old age is best approximated by the Erlang probability distribution. The Erlang distribution describes the probability of several successive random events occurring by the given time according to the Poisson process, which allows to predict the number of critical driver events.ResultsHere we show that the Erlang distribution is the only classical probability distribution that can adequately model the age distribution of incidence for all studied childhood and young adulthood cancers, in addition to cancers of old age.ConclusionsThis validates the Poisson process as the universal law describing cancer development at any age and the Erlang distribution as a useful tool to predict the number of driver events for any cancer type. The Poisson process signifies the fundamentally random timing of driver events and their constant average rate. As waiting times for the occurrence of the required number of driver events are counted in decades, it suggests that driver mutations accumulate silently in the longest-living dividing cells in the body - the stem cells.

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Geographic Variation in Colorectal Cancer Incidence and the Disparities in the Prevalence of Modifiable Risk Factors Across Canada

Journal of Global Oncology ◽

10.1200/jgo.18.36600 ◽

2018 ◽

Vol 4 (Supplement 2) ◽

pp. 15s-15s

Author(s):

J. Tung ◽

C. Politis ◽

J. Chadder ◽

J. Han ◽

J. Niu ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

New Brunswick ◽

Geographic Variation ◽

Cancer Incidence ◽

Incidence Rates ◽

Modifiable Risk Factors ◽

Colorectal Cancer Incidence ◽

Incident Cases ◽

Cancer Incidence Rates

Background: Colorectal cancer is the third most common cancer worldwide. There is wide geographic variation in incidence with rates varying ten-fold between high- and low-income countries. This heavy burden can be mitigated given previous research has estimated that nearly half of all colorectal cancer cases could have been prevented through healthier diets and physically active lifestyles. In Canada, there is considerable geographic variation in age-adjusted incidence rates for colorectal cancer between jurisdictions, greater than that seen for many other cancers. These wide variations likely reflect differences in the prevalence of risk factors across provinces and territories. Aim: To describe the extent of the variation in colorectal cancer incidence rates across Canada and the disparities in the prevalence of modifiable risk factors across jurisdictions known to contribute to this burden. Methods: Colorectal cancer incident cases were obtained from the Canadian Cancer Registry; 2014 was used for provinces (except Quebec where 2010 was the most recent year available) and years 2012 to 2014 were combined to achieve more stable rates for the territories, which are much smaller in population. Data on four known modifiable risk factors for colorectal cancer (excess weight, physical inactivity, alcohol intake and low fruit and vegetable consumption) were obtained from the 2015-16 combined Canadian Community Health Survey. Results: Findings suggest that there is a north-south and east-west gradient in colorectal cancer modifiable risk factors in Canada. For instance, the percentage of adults with excess body weight ranged from 56.8% in British Columbia (west) to 73.1% in New Brunswick (east) and the percentage of adults not meeting physical activity guidelines ranged from 31.8% in Yukon (north) to 50.3% in New Brunswick (east). Generally, this pattern also reflects colorectal cancer incidence rates. The highest prevalence of modifiable risk factors and rates of colorectal cancer are typically in the northern (territories) and eastern provinces of Canada. Conclusion: The global burden of colorectal cancer is expected to increase by nearly 60% by 2030; therefore, targeted interventions are needed to ensure there is not a widening gap in colorectal cancer burden worldwide. Based on current knowledge, the most effective approaches to reduce the burden of colorectal cancer include: 1) adopting public policies that make healthy choices easier and create healthier environments where people live, work and play, and 2) continuing emphasis on screening and early detection. Strategic approaches to addressing modifiable risk factors, as well as mechanisms for detecting colorectal cancer before it develops, have the potential to translate into positive effects on population health and less people developing and dying from cancer.

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The Erlang distribution approximates the age distribution of incidence of childhood and young adulthood cancers

PeerJ ◽

10.7717/peerj.11976 ◽

2021 ◽

Vol 9 ◽

pp. e11976

Author(s):

Aleksey V. Belikov ◽

Alexey Vyatkin ◽

Sergey V. Leonov

Keyword(s):

Probability Distribution ◽

Poisson Process ◽

Old Age ◽

Young Adulthood ◽

Age Distribution ◽

The Body ◽

Driver Mutations ◽

Erlang Distribution ◽

Cancer Type ◽

Global Parameter

Background It is widely believed that cancers develop upon acquiring a particular number of (epi) mutations in driver genes, but the law governing the kinetics of this process is not known. We have previously shown that the age distribution of incidence for the 20 most prevalent cancers of old age is best approximated by the Erlang probability distribution. The Erlang distribution describes the probability of several successive random events occurring by the given time according to the Poisson process, which allows an estimate for the number of critical driver events. Methods Here we employ a computational grid search method to find global parameter optima for five probability distributions on the CDC WONDER dataset of the age distribution of childhood and young adulthood cancer incidence. Results We show that the Erlang distribution is the only classical probability distribution we found that can adequately model the age distribution of incidence for all studied childhood and young adulthood cancers, in addition to cancers of old age. Conclusions This suggests that the Poisson process governs driver accumulation at any age and that the Erlang distribution can be used to determine the number of driver events for any cancer type. The Poisson process implies the fundamentally random timing of driver events and their constant average rate. As waiting times for the occurrence of the required number of driver events are counted in decades, and most cells do not live this long, it suggests that driver mutations accumulate silently in the longest-living dividing cells in the body—the stem cells.

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