ALCOHOLALCOHOLANDAND

COLORECTAL CANCERCOLORECTAL CANCER

Adrian CakraMBBS 4

Colorectal UnitTQEH

FOCUS

BEER, WINE, SPIRITS AND HOW THEY INFLUENCE THE RELATIVE RISK OF DEVELOPING COLORECTAL

CANCER

“HOW MUCH IS TOO MUCH?”

STUDIES

1. A Pedersen, C Johansen, M Grønbæk (Copenhagen, 2002) Randomly selected sample of 15491 men & 13641 women. Assessment of weekly intake of beer, wine, and spirits. Development of colorectal cancer during follow-up

2. JC Anderson, et.al (New York, 2005) Hand-picked samples of 2291 patients presenting for

colonoscopy (screening). Known risk factors for colorectal neoplasia & alcohol

drinking pattern. Colonoscopy findings.

STUDIES

3. CR Sharpe, J Seimiatycki, B Rachet (Montréal, 2002) Hand-picked samples of 585 patients with diagnosed

colorectal cancer. Information obtained as soon as possible after

diagnosis. Assessing alcohol drinking pattern.

4. A Moskal, et.al. (Lyon, 2006) Meta-analysis. Journal articles published between 1990 and 2005. Analysing association between relative risk and various

alcohol intake levels.

BRIEF OVERVIEW

1 in 8 Australian adults drank at a high risk level (ABS, 2005)

A standard drink : +/- 10g of pure alcohol

Most men prefer : beer Most women prefer : wine

Annual consumption in average:– Beer : 4.6L per person– Wine : 3.1L per person– Spirits : 2.1L per person

LOWLOW MODERATEMODERATE HIGHHIGH

<3 daily<3 daily 4 - 6 daily4 - 6 daily >7 daily>7 daily

STUDY 1

RESULTS:

QUANTITY RR (COLON) RR (RECTUM) Low 1.1 1.2 Moderate 1.1 1.4

Be

er

High 1.2 1.8 Low 0.9 0.9 Moderate 0.9 0.9

Win

e

High 0.5 0.9 Low 1.1 1.0 Moderate 1.3 1.3

Sp

irit

High 1.5 1.4

STUDY 1

1.6 1.4 1.2 1.0 0.8 0.6 0.4 0 1-7 8-21 22-35 >35

RR

Alcohol Consumption (drinks/week)

Non-wine

Wine

STUDY 1

– In heavy alcohol consumption, the association between alcohol and rectal cancer is more prominent in comparison with colon cancer.

– Risk of developing colon cancer is not much different among different types of alcohol.

– Heavier beer and spirits intake is associated with an increase in the relative risk of developing rectal cancer.

– Slight decrease in relative risk of developing rectal cancer associated with wine consumption.

– Those who include wine in their alcohol intake have significantly reduced relative risk of developing rectal cancer.

STUDY 2

RESULTS:

QUANTITY RR (COLON + RECTUM) Low 1.0 Moderate 0.9

Beer

High 2.4 Low 1.0 Moderate 0.6

Win

e

High 0.5 Low 1.0 Moderate 0.9

Sp

irit

High 2.5

STUDY 2

PATHOLOGICAL DISTRIBUTIONPATHOLOGICAL DISTRIBUTION

PATHOLOGY ABSTAINER BEER WINE SPIRITS High-grade dysplasia 0.7% 0.3% 0.5% 0.4% Tubular adenomas 13.1% 11.5% 9.7% 11.1% Villous adenomas 2.9% 2.0% 1.2% 3.1% Malignant polyp 0.2% 0.7% 0.2% 0.9% Adenocarcinoma 0.7% 0.7% 0.3% 0.9% Significant neoplasia 10.7% 10.8% 5.9% 14.7%

STUDY 2

– Wine in moderate quantity may decrease the likelihood of developing colorectal cancer up to half compared to higher quantity.

– Beer and spirits in high quantity may increase the likelihood of developing colorectal cancer by more than twofold compared to lower quantity.

STUDY 3

RESULTS:

Distal colon is more likely to get affected than proximal colon with any alcohol type.

QUANTITY RR (COLON) RR (RECTUM) Low 1.0 1.1 Moderate 1.4 1.7

Be

er

High 2.4 1.5 Low 0.9 1.1 Moderate 0.8 1.5

Win

e

High 0.9 0.2 Low 1.1 1.4 Moderate 1.6 1.5

Sp

irit

High 1.6 1.9

STUDY 3

– In relation to alcohol, the distal colon is more likely to develop neoplasia in comparison with the proximal colon.

– Heavy beer consumption has the strongest relationship with cancer of the distal colon and rectum.

– Risk of developing colorectal cancer increases with longer period of alcohol consumption (ie. start drinking at earlier age) regardless the alcohol type.

– Wine consumption relates to a decrease in relative risk of developing rectal cancer.

STUDY 4

Comparison between high and low alcohol intake. 16 studies with more than 6,300 patients included.

FINDINGS:– Positive association to colon cancer in men (RR 1.64)

and women (RR 1.23)– Positive association to rectal cancer in men (RR 1.79)

and women (RR 1.39)– Ethanol in alcoholic beverages is the significant factor,

not the type of the beverages itself.

WHICH ONE IS BETTER?

WINEWINE

BEERBEER

SPIRITSSPIRITS

HOW MUCH?

BEER & SPIRITSBEER & SPIRITS30g30g of alcohol daily is the maximum safety limit in relation

to the relative risk of developing colorectal cancer. Consumption above that level may increase the relative risk of developing colorectal cancer significantly (up to

twofold).

WINE (especially RED)WINE (especially RED)10g - 30g10g - 30g of alcohol daily is believed to be the optimum quantity to get the benefit of wine in reducing the relative

risk of developing colorectal cancer (up to half). Consumption above that level is not proven to be

beneficial.

HOW MANY?

BEER (LOW STRENGTH)BEER (LOW STRENGTH) BEER (FULL BEER (FULL STRENGTH)STRENGTH)

SPIRITSSPIRITS PORT/SHERRYPORT/SHERRY

WINEWINE SPARKLING WINESPARKLING WINE

425mL 425mL 425mL

30mL 30mL 30mL

375mL 375mL

60mL 60mL 60mL

100mL 100mL100mL 180mL 180mL

IN SUMMARY

Low to moderate consumption of alcohol in general does not increase the relative risk of developing colorectal cancer.

Low to moderate consumption of wine (especially red) in general may lower the relative risk of developing colorectal cancer.

High consumption of alcohol in general may increase the relative risk of developing colorectal cancer (especially rectal cancer).

Beer is associated with significantly higher relative risk of developing colorectal cancer in high quantity drinkers, men in particular.

It is generally safe to drink up to 30g30g of alcohol daily, although the lesser the better.

Drink red wine!Drink red wine!

POLYPHENOLS

Administration of 50mg/kg red wine polyphenols to rats Induction of colon carcinogenesis Polyphenol-treated rats had lower tumour yield in

comparison with control rats Chemopreventive against colon cancer ?

POLYPHENOLS

POLYPHENOLS

DOWN-REGULATED GENES AFTER POLYPHENOL TREATMENT

CELL SURFACE ANTIGENS

GENE EXPRESSION CONTROL

RECEPTORS & SIGNAL TRANSDUCTION

GROWTH FACTORS

ENERGY METABOLISM

TRANSPORT & BINDING PROTEINS

DAMAGE & STRESS RESPONSE

CHOLESTEROL & LIPID METABOLISM

XENOBIOTIC METABOLISM

INFLAMMATORY & IMMUNE RESPONSES

UNASSIGNED

CELL STRUCTURE

CELL CYCLE

METABOLIC ENZYMES

Courtesy of Dolara, P, et al. (2004)

REFERENCES

Anderson, JC, et al. (2005) Prevalence and Risk of Colorectal Neoplasia in Consumers of Alcohol in a Screening Population. American Journal of Gastroenterology. Vol.100. pp.2049-2055.

Australian Bureau of Statistics (2006) Alcohol Consumption in Australia: A Snapshot, 2004-05. Commonwealth of Australia. Available from <http://www.abs.gov.au/ausstats/abs@.nsf/mf/4832.0.55.001/> Accessed on 12 August 2007.

Bongaerts, BWC, et al. (2007) Alcohol consumption and distinct molecular pathways to colorectal cancer. British Journal of Nutrition. Vol.97. pp.430-434.

Dolara, P, et al. (2005) Red wine polyphenols influence carcinogenesis, intestinal microflora, oxidative damage and gene expression profiles of colonic mucosa in F344 rats. Journal of Mutation Research. Vol.591. pp.237-246.

Moskal, A, et al. (2006) Alcohol intake and colorectal cancer risk: A dose-response meta-analysis of published cohort studies. International Journal of Cancer. Vol.120. pp.664-671.

Pedersen, A, et al. (2003) Relations between amount and type of alcohol and colon and rectal cancer in a Danish population based cohort study. Gut: International Journal of Gastroenterology and Hepatology. Vol.52. pp.861-867.