What is the current evidence between alcohol and cancer?STAP International Conference on Alcohol, Health and Policy3 October 2014 Giota Mitrou PhD MSc Head of Research Funding & Science Activities

Outline

§ WCRF network & WCRF International§ The case for cancer prevention§ The Continuous Update Project process§ The Continuous Update Project evidence§ Mechanisms§ Research issues & future research directions§ Conclusions

WCRF Network

§American Institute for Cancer Research (1982)§WCRF UK (1990)§WCRF Netherlands (1994)§WCRF Hong Kong (1997)

Members of the World Cancer Research Fund network of cancer charities witha global reach, dedicated to the prevention of cancer through diet, weight and physical activity:

WCRF International (1999) leads and unifies the network of cancer charities

Vision: to live in a world where no one develops a preventable cancer

WCRF International§ Supports the scientific community in their research§ Stimulates and nurtures research and innovation in cancer

prevention and survivorship§ Encourages more young scientists to enter the field§ Encourages scientists to cite us in scientific papers and to

help disseminate our information§ Encourages and enables governments and policymakers to

adopt and implement effective policy actions§ Engages and influences decision-makers to involve us in the

development of their policies on cancer prevention and non-communicable diseases

The case for cancer prevention

Global Alcohol Consumption

Source: WHO's annual World Health Statistics report 2010

Europe: In men about 10% and in women about 3% of all cancers attributable to alcohol Devaux and Sassi, OECD Publishing, 2013.

Alcohol and disease

§ 3rd highest risk factor for disease & mortality in Europe

§ Light to moderate alcohol consumption might reduce cardiovascular risk especially CHD mortality (reverse causation and confounding cannot be excluded)

§ High consumption might precipitate myocardial ischemia/infarction and coronary death

§ Since 1998 IARC classified alcohol as Group 1 carcinogen

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1970 1980 1990 2000 2010 2020 2030 2040

Num

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Estimated global number of new cases of cancer (actual and predicted)

Data from Parkin et al, Pisani et al, Globocan 2012, IARC

International Agency for Research on Cancer

“We are not going to be able to address this problem by simply improving the treatment of the disease…Prevention is absolutely critical and is somewhat neglected…Tidal wave of cancer and restrictions on alcoholand sugar need to be considered” – Chris Wild, Director

WCRF cancer preventability estimates from alcohol intake

Cancer USA(%)

UK(%)

Brazil (%)

China(%)

Oesophagus 34 51 23 11Mouth, Pharynx & Larynx

27 41 17 10

Liver 15 17 6 6Colorectum 5 7 2 1Breast 11 22 6 1Source: http://www.wcrf.org/cancer_statistics/preventability_estimates/preventability_estimates_food.php

The Continuous Update Project process

Continuous Update Project§ The CUP analyses global cancer prevention and survival research

linked to diet, nutrition and physical activity. Among experts worldwide it is a trusted, authoritative scientific resource, which underpins current guidelines and policy for cancer prevention

§ It ensures the WCRF network Recommendations for Cancer Prevention are based on the latest evidence

§ The CUP is produced in partnership with the American Institute for Cancer Research, World Cancer Research Fund UK, World Cancer Research Fund NL and World Cancer Research Fund HK

Continuous Update Project: CUP§ Agreed process for systematically

reviewing evidence for 2007 Report§ Researchers at Imperial College London:qCUP database of epi researchqSystematically review the evidence§ Expert Panel:qDraw conclusionsqMake recommendations

People§Currently more than 100

scientists from 17 countries around the world§ International panel of 12

experts§Researchers, peer

reviewers, advisers

Hierarchy of evidence

§ Meta-analysis§ RCT§ Cohort§ Case control§ Ecological§ Opinion

Grading criteriaPredefined requirements for;§ Number and types of studies§ Quality of exposure and outcome assessment§ Heterogeneity within and between study types§ Exclusion of chance, bias or confounding§ Biological gradient§ Evidence of mechanisms§ Size of effect

Grading the evidenceDecreases risk

Increases risk

Strong evidence

Convincing

Probable

Limited evidence

Limited -suggestiveLimited – no conclusion

Strong evidence

Substantial effect on risk unlikely

Basis for recommendations

The Continuous Update Project: what is the current evidence

Assessing alcoholic drink intake§ Alcohol is a common term for ethanol § Alcoholic drinks include beer, wine and

spirits – ethanol concentration varies§ Measures of exposure:q Number of alcoholic drinks/time period (eg

per day or per week)q Ethanol intake (g or ml)/time period

Breast Cancer Report 2010

Breast Cancer Report 2010

Postmenopausal Breast Cancer & Alcohol

Relative risk:

8% per 10g ethanol/d

No. of studies: 13

Postmenopausal Breast Cancer & AlcoholHigh vs Low intake

Direction of effect: increased risk

Range: 0g to >60g ethanol/d

No. of studies: 13

Colorectal Cancer Report 2011

Colorectal Cancer & Alcohol by sexMen:Relative risk:

11% per 10g ethanol/d

No. of studies: 7

Women: Relative risk:

7% per 10g ethanol/d

No. of studies: 2

Pancreatic Cancer Report 2012

Strong evidence for alcohol & other cancersSecond Expert Report 2007

Cancer site Increased risk Intake

Mouth, pharynx, larynx 24% 1 drink/week

Oesophageal 4% 1 drink/week

Liver 10% 10g/day

Note: Multiplicative synergistic effects for combined exposure to alcohol drinking and tobacco smoking and upper respiratory tract cancers

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Foods containing dietary fibreAflatoxinsNon-starchy vegetables1

Allium vegetablesGarlicFruits2

Foods containing lycopeneFood containing selenium3

Red meatProcessed meatCantonese-style salted fishDiets high in calcium4

Salt, salted and salty foodsGlycaemic loadArsenic in drinking waterMaté

CoffeeBeta-carotene6

Physical activityBody fatnessAdult attained heightGreater birth weightLactation

Alcoholic drinks5

Convincing decreased riskProbable decreased risk

Probable increased riskConvincing increased risk

Substantial effect on risk unlikely

CUP matrix of strong evidence

Recommendation for cancer prevention

Year Publication2010 Breast2011 Colorectum2012 Pancreas2013-14 Endometrium, ovary, breast cancer survivors, prostate

2014-15 Bladder, kidney, liver, gallbladder2015-16 Stomach, oesophagus, lung2016-17 Mouth, pharynx, larynx, nasopharynx, breast, colorectum

2017 Review Recommendations for Cancer Prevention

Publications timetable

Mechanisms

Alcohol Cancer

Biological/Cellular Pathway?

Mechanisms§ Ethanol (acetaldehyde) is human carcinogen (Group

1, IARC)

§ Ethanol metabolism activates other pro-carcinogens eg ROS

§ Disrupts folate metabolism- important in DNA synthesis and repair

§ Suppresses the immune system which may facilitate tumour cell spread

Cancer site specific mechanisms§ Digestive tract cancers:

q Variation in ethanol metabolising enzymes (ADH, ALDH) modulates cancer risk

§ Oral cavity, larynx, pharynx and oesophagus cancers:q Synergistic effect of carcinogens in tobacco and alcoholic

drinks lead to mucosal hyperproliferation§ Liver cancer:

q Mediates cirrhosis of the liver which is associated with cancer development

§ Breast cancer:q Increases oestrogen and androgen levels/induces expression

of ER/PR hormone receptors

Research issues and future research directions§ Better standardisation across studies in assessing alcohol

intake, timing and pattern of exposure eg binge drinking§ Better characterisation of cumulative lifetime exposure (better

info on age at start of drinking, assessing alcohol intake during lifecourse, stopping drinking and risk)§ Interactions with other lifestyle factors eg body weight or with

nutrients eg folate§ Better understanding cancer site specific mechanisms eg

epigenetic mechanisms, main effect modifiers§ Understanding individual attitudes towards alcohol drinking

and cultural and social influences for tailored public health messages

Conclusions§ CUP is trusted, authoritative scientific resource, which underpins current

guidelines and policy for cancer prevention§ CUP database of evidence largest of its kind on diet, nutrition and

physical activity§ Enables comprehensive recommendations for cancer prevention based

on the most up-to-date scientific evidence§ Strong evidence that alcohol causes cancer of:

q Breast q Colorectal q Mouth, pharynx, larynxq Oesophagealq Liver

Conclusions§ Risk increases in dose-dependent manner-higher amount,

higher risk of cancer development

§ Consumption of any amount of alcohol increases cancer risk

§ Reducing consumption or even better avoiding alcohol completely will help reduce cancer risk

§ Important implications for prevention and alcohol policy

WCRF cancer prevention recommendation

For further information

@wcrfintfacebook.com/wcrfint

www.wcrf.org

Giota Mitrou PhDHead of Research Funding & Science Activities

g.mitrou@wcrf.org