Cancer types with high numbers of driver events are largely preventable

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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Anthropogenic risk factors as the major cause of cancer driver events

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 in agricultural populations

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2019-59-9-837 ◽

2020 ◽

pp. 837-837

Author(s):

K. . Togawa

Keyword(s):

Risk Factors ◽

General Population ◽

Cohort Studies ◽

Health Effects ◽

Cancer Incidence ◽

Lower Prevalence ◽

International Consortium ◽

Adverse Health Effects ◽

Specific Cancer ◽

Cancer Types

Agricultural workers can be exposed to a wide variety of agents (e.g. pesticides), some of which may have adverse health effects, such as cancer. To study the health effects of agricultural exposures, an international consortium of agricultural cohort studies, AGRICOH, was established. The present analysis compared cancer incidence between the AGRICOH cohorts and the general population and found lower overall cancer incidence in the AGRICOH cohorts, with some variation across cohorts for specific cancer types. The observed lower cancer incidence may be due to healthy worker bias or lower prevalence of risk factors in the agricultural populations. Further analysis is underway.

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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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Fitting the Erlang distribution to cancer incidence by age may predict key carcinogenic events

10.1101/060970 ◽

2016 ◽

Author(s):

Aleksey V. Belikov

Keyword(s):

Cancer Progression ◽

Cancer Incidence ◽

Age Of Onset ◽

Erlang Distribution ◽

Time Interval ◽

Progression Rate ◽

Cancer Type ◽

Growth Equations ◽

Cancer Types ◽

Multiple Hit

AbstractCancer is the second-leading cause of death worldwide, after cardiovascular diseases. Cancers arise from various cells and organs at different ages and develop at different rates. However, the reasons for this variation in the cancer progression rate and the age of onset are poorly understood. Especially puzzling is the late-life decrease in cancer incidence, which cannot be explained by previously proposed power law or exponential growth equations. By using the latest publicly available USA cancer incidence statistics, comprised of 20 million cancer cases documented over 14 years, I show that cancer incidence by age closely follows the Erlang probability distribution (R2=0.9543-0.9999), which is a special case of the gamma distribution. The Erlang distribution describes the probability y of k independent random events occurring by the time x, but not earlier or later, with each event happening on average every b time intervals. This fits well with the multiple-hit hypothesis, and potentially allows to predict the number k of key carcinogenic events and the average time interval b between them, for each cancer type. Moreover, the amplitude parameter A likely predicts maximal populational susceptibility to a given type of cancer. These parameters are estimated for 20 most common cancer types, and provide clues for further research on cancer development.

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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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Do Diet and Lifestyles Play a Role in the Pathogenesis of NMSCs?

Nutrients ◽

10.3390/nu12113459 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3459

Author(s):

Nevena Skroza ◽

Ilaria Proietti ◽

Anna Marchesiello ◽

Salvatore Volpe ◽

Veronica Balduzzi ◽

...

Keyword(s):

Physical Activity ◽

Risk Factors ◽

Protective Factor ◽

Statistical Significance ◽

Control Group ◽

Modifiable Risk Factors ◽

Face To Face ◽

Skin Cancers ◽

Reduced Physical Activity ◽

Cancer Types

Background and Aims: Literature highlights the role of risk factors like age, body mass index (BMI), tobacco smoking, alcohol intake and diet in the pathogenesis of several cancer types but little is known for non-melanoma skin cancers (NMSC). The aim of this epidemiological study was to evaluate the correlation between modifiable risk factors (BMI, metabolic panel, diet, lifestyle, medical history) and not modifiable risk factors (gender, age) and NMSC development. Methods: From February 2018 to September 2019, 162 patients affected by NMSC were compared to a group of 167 controls. A univariate and multivariate analysis was conducted to elaborate the data collected through face-to-face interviews. Results: While our evidence did not always reach statistical significance, NMSC study group patients exhibited high rates of analyzed risk factors (male gender aging over 55 years, high BMI, reduced physical activity) compared to the control group. Conclusions: Our study indicates that practicing more than 30 min of physical activity daily could be a protective factor against the NMSC onset. Other risk factors were not correlated with NMSC, but more evidence is needed to establish a possible link.

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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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