Alcohol and Cancer

1
Alcohol and Cancer
- EPI 242 Cancer Epidemiology, Nov 16, 2009 -

• Nai-chieh Yuko You, M.S., Ph.D.

2
Outlines

• Introduction
• Health effect
• Epidemiologic studies
• Alcohol and Cancer
• Current interests and issues of alcohol and
  cancer research

3
Introduction
4
Alcohol Beverages

• Drinks made by fermenting fruit juices, sugars,
  and fermentable carbohydrates with yeast to form
  alcohol.
• The predominant types of commercially produced
  alcoholic beverages are beer, wine and spirits.
• The main components of all alcoholic beverages
  are ethanol and water beers also contain
  substantial amounts of carbohydrates. Some
  components and occasional contaminants include
  known and suspected carcinogens. Beers and wines
  also contain vitamins and other nutrients which
  are usually absent from distilled spirits.

5
Alcohol by Volume (ABV)
Type of beverage ABV (w/w in )
beer, cider, and Perry 4-6
wine 9-13
spirits (e.g. brandy, gin, rum, vodka, whisky) made by distilling fermented liquor 38-45
liqueurs made from distilled spirits, sweetened and flavored 20-40
fortified wines (aperitif wines, Madeira, port, sherry) made by adding spirit to wine 18-25
6
Trends in Ethanol Consumption in the US, 1960-97
Source NIAAA, NIH
7
Percent Drinking Alcohol (1984 and 1995)
Caetano and Clark, J Stud Alcohol, 1998
8
Prevalence of Alcohol Use

• Almost half of Americans aged 12 and older
  reported being current drinkers of alcohol in the
  2000 survey (46.6). This translates to an
  estimated 104 million people.
• About 35 of the adult US population abstains
  from alcohol use, about 60 are occasional to
  moderate drinkers, and about 5 to 7 are
  diagnosable with alcohol abuse or dependence
  (NIAAA, 1997). Of the some 16 million Americans
  who meet the diagnostic criteria for abuse or
  dependence, only about 1.5 million seek and
  receive treatment (SAMHSA, 2003).
• Alcohol consumption causes some 100,000 deaths
  annually in the US, including more than 16,000
  alcohol related traffic fatalities (Meister et
  al., 2000 NIAAA, 2000).

9
Health Effect
10
Health Effect

• Cardiovascular Disease
• Cancers (upper aerodigestive tract cancer, HCC,
  colorectal cancer and breast cancer)
• Obesity
• Diabetes
• Birth defect
• Breastfeeding
• Aging
• Alcohol abuse and dependence
• Hepatic effect (Alcohol-related liver disease,
  included cirrhosis and alcoholic hepatitis )
• Genetic and related effects
• Injury/Accident
• Total mortality

11
The proposed model for alcohol consumption,
health and social behavior
The relationship of average volume of alcohol
consumption and patterns of drinking to burden of
disease an overview Jürgen Rehm , Robin Room ,
Kathryn Graham , Maristela Monteiro , Gerhard
Gmel Christopher T. Sempos Addiction
Volume 98 Issue 9 Page 1209  - September 2003
12
Global Mortality Burden (deaths in thousands)
Attributable to Alcohol by Major Disease
Categories 2000
Eur Addict Res 20039157164 Global Burden of
Disease Attributable to Alcohol Jürgen Rehma,
Robin Room, Maristela Monteiro, Gerhard Gmel,
Kathryn Graham, Nina Rehn, Christopher T.
Sempos, David Jernigan
13
Alcohol-Attributable Deaths (in thousands) in
2000 by Disease and Subregion
Eur Addict Res 20039157164 Global Burden of
Disease Attributable to Alcohol Jürgen Rehma,
Robin Room, Maristela Monteiro, Gerhard Gmel,
Kathryn Graham, Nina Rehn, Christopher T.
Sempos, David Jernigan
14
Global burden of disease (DALYs in thousands)
attributable to alcohol by major disease
categories 2000
Eur Addict Res 20039157164 Global Burden of
Disease Attributable to Alcohol Jürgen Rehma,
Robin Room, Maristela Monteiro, Gerhard Gmel,
Kathryn Graham, Nina Rehn, Christopher T.
Sempos, David Jernigan
15
Alcohol-related disease burden in DALYs (in
thousands) by disease category and region
Eur Addict Res 20039157164 Global Burden of
Disease Attributable to Alcohol Jürgen Rehma,
Robin Room, Maristela Monteiro, Gerhard Gmel,
Kathryn Graham, Nina Rehn, Christopher T.
Sempos, David Jernigan
16
Alcohol and Cancer

• Nearly 100 years ago, Lamy noticed an increased
  incidence of esophageal cancer in absinth
  drinkers (Lamy, 1910).
• Since then, extensive epidemiological data has
  accumulated which identified alcohol as a major
  risk factor for UADT cancer
• Furthermore, substantial epidemiological evidence
  accrued over the past 50 years has shown that
  alcohol contributes to the development of these
  cancers.
• In 1988, IARC concluded that there is sufficient
  evidence that alcohol beverage are carcinogenic
  in humans.
• Nevertheless, the mechanisms underlying
  alcohol-related cancer development remain largely
  unclear.

17
9 Possible Mechanisms How Alcohol Intake
Increase Cancer Risk According to Blot et al
(1992)

• 1. Contain congeners and other contaminants that
  may be carcinogenic
• 2. Generated metabolites that are carcinogenic to
  humans
• 3. Act as solvent, increasing penetration of
  other carcinogens into target tissue
• 4. Reduce intake and bioavailability of nutrition
  
• 5. Inhibit the detoxification of carcinogenic
  compounds
• 6. Catalyze the metabolic activation of some
  compounds into carcinogens
• 7. Affect hormonal status
• 8. Increase cellular exposure to oxidants
• 9. Suppress immune function

18
Selected Chemical Compounds in Alcoholic beverage
which have been found to be carcinogenic
compound Identified in Identified in Identified in IARC evaluation IARC evaluation IARC evaluation
compound Beer Wine Spirits human animal Overall
Aflatoxin S S 1
Arsenic S L 1
Asbestos S S 1
Benzene S S 1
Chromium S S 1
Nickle S S 1
Benz(a)anthracene ND S 2A
Benzo(a)pyrene ND S 2A
Cadmium L S 2A
Formaldehyde L S 2A
N-Nitrosodiethylamine ND S 2A
N-Nitrosodimethylamine ND S 2A
SSufficient LLimited IInadequate NDNo data
19
IARC

• Group 1 The agent (mixture) is carcinogenic to
  humans. The exposure circumstance entails
  exposures that are carcinogenic to humans
• Group 2
• Group 2A The agent (mixture) is probably
  carcinogenic to humans.The exposure circumstance
  entails exposures that are probably carcinogenic
  to humans.
• Group 2B The agent (mixture) is possibly
  carcinogenic to humans.The exposure circumstance
  entails exposures that are possibly carcinogenic
  to humans.
• Group 3 The agent (mixture or exposure
  circumstance) is not classifiable as to its
  carcinogenicity to humans
• Group 4 The agent (mixture) is probably not
  carcinogenic to humans.

20
9 Possible Mechanisms How Alcohol Intake
Increase Cancer Risk According to Blot et al
(1992)

• 1. Contain congeners and other contaminants that
  may be carcinogenic
• 2. Generated metabolites that are carcinogenic to
  humans
• 3. Act as solvent, increasing penetration of
  other carcinogens into target tissue
• 4. Reduce intake and bioavailability of nutrition
  
• 5. Inhibit the detoxification of carcinogenic
  compounds
• 6. Catalyze the metabolic activation of some
  compounds into carcinogens
• 7. Affect hormonal status
• 8. Increase cellular exposure to oxidants
• 9. Suppress immune function

21
Alcohol Metabolism

• Source Klaassen,CD (1998) Casarett
  Doull's Toxicology The basic science of poisons,
  fifth edition

22
Acetaldehyde-derived DNA Adducts
Chemical Structures of Deoxyguanosine, the DNA
Base that is the target for acetaldehyde, as well
as the acetaldehyde-derived DNA lesions. The
atoms in red represent the acetaldehyde-derived
chemical modifications.
The 2007 International Agency for Research on
Cancer Working Group on alcohol and cancer
specifically noted the substantial mechanistic
evidence supporting a causal role for
acetaldehyde in alcohol-related esophageal cancer
Baan et al. (2007) Carcinogenicity of alcoholic
beverages. Lancet Oncol 8 292293 Brooks PJ et
al. PLoS Med. 2009 Mar 246(3)e50
23
9 Possible Mechanisms How Alcohol Intake
Increase Cancer Risk According to Blot et al
(1992)
1. Contain congeners and other contaminants that
may be carcinogenic 2. Generated metabolites
that are carcinogenic to humans 3. Act as
solvent, increasing penetration of other
carcinogens into target tissue 4. Reduce intake
and bioavailability of nutrition 5. Inhibit the
detoxification of carcinogenic compounds 6.
Catalyze the metabolic activation of some
compounds into carcinogens 7. Affect hormonal
status 8. Increase cellular exposure to oxidants
9. Suppress immune function
24
Other Possible Mechanisms

• Direct toxic effect due to highly concentrated
  alcoholic beverage on the epithelium
• Enhance reflux
• Decrease several other phase II enzyme levels,
  included liver glutathione and SAM level
• Inhibit the activity of DNA methylase found in
  animal studies, but cant confirm in human.

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Animal Human researches

• Animal studies
• Correlation Studies
• Cohort and Case-Control Studies

26
Animal Study

• The results of animal experiment on alcohol and
  cancer depend on the experimental design, type of
  carcinogen used, its time, duration of exposure,
  dosage and administration route.
• When alcohol applied locally to oral and
  esophageal mucosa, it increases the occurrence of
  tumor probably due to irritant effect of alcohol
  (Seitz et al, 1998)
• When ethanol is given systematically, stimulating
  effect on chemical induced carcinogenesis is
  noted. (Seitz et al, 1998) When alcohol is given
  chronically to rodents have shown that life-time
  exposure to alcohol do not develop more cancer
  than do controls.
• Most of animal studies were expected to find HCC,
  however, they found the rate of extra hepatic
  tumor increased, especially UADT.

27
Correlation Studies

• Per capita alcohol consumption was associated
  with cancer mortality, including cancer of
  esophagus (Tuyns et al, 1976), gastrointestine
  (Konoet al, 1979), larynx (Tuyns et al, 1976),
  and pancreas (Qiao et al, 1988).
• Time trends was found in per capita alcohol
  consumption and mortality from esophageal and
  laryngeal cancer (Tuyns et al, 1976), and
  colorectal cancer (McMichael et al, 1979).

28
Cohort/Case Control Studies

• Oral and pharyngeal cancer
• Esophageal cancer
• Stomach cancer
• Liver cancer
• Colorectal cancer
• Lung cancer
• Breast cancer

29
Cancers of Upper Aerodigestive Tract (UADT)

• Alcohol strong risk factor for cancers of the
  oral cavity and pharynx, esophagus, and larynx
• Earliest report,1836 by Boston surgeon, J.C.
  Warren who described a case of tongue cancer in a
  tobacco chewer with a predisposition due to
  chronic use of spirits
• Earliest association, an excess of esophageal
  cancer among alcoholics in Paris in 1910
• 25-80 are attributable to alcohol
• Smoking also strong risk factor risk greatest
  for heavy drinkers and smokers

30
Cancer of Oral Cavity and Pharynx

• The mucosa of the oral cavity and pharynx
  (excluding the nasopharynx) comes into close
  contact with alcohol upon ingestion.
• Biological plausible that alcohol directly affect
  carcinogenesis in these sites via physiochemical
  or metabolic effects.
• Epidemiological studies clearly indicate that
  drinking of alcoholic beverages is causally
  related to cancers of the oral cavity and pharynx
  (excluding the nasopharynx). There is no
  indication that the effect is dependent on type
  of beverage.

31
Relative Risks of Alcohol Consumption for Oral
Cancer
Bagnardi et al , British Journal of Cancer 2001
32
Alcoholic Beverage Use and Risk of Oral Cancer in
Puerto Rico by Gender

• Subjects Puerto Rican men and women, aged 21-79
• Cases - 286 males, 249 females
• Controls - 417 males, 614 females
• ORs adjusted for tobacco, diet, education, age

Hayes et al., Cancer Causes Control, 1999
33
Liquor Use and Risk of Oral Cancer in Puerto Rico
by Concentration
Huang et al., Am J Epidemiol, 2003
34
RR Of Oral Cancer According to Daily Consumption
of Tobacco and Alcohol
Alcohol Consumption (ethanol/day) Tobacco Consumption (in g per day) Tobacco Consumption (in g per day) Tobacco Consumption (in g per day) Tobacco Consumption (in g per day)
Alcohol Consumption (ethanol/day) 0 lt20 20-39 40
0 1.00 1.63 1.62 3.40
lt0.4oz(9.5g) 1.66 1.89 3.29 3.35
0.4-1.5(9.5-36g) 1.88 4.85 4.84 8.20
1.6 oz(36g) 2.27 4.79 9.97 15.6
Number of cases 26 44 248 143
Tuyns et al, 1977
35
Cancer of Esophagus

• Alcohol drinking has been classified as a risk
  factor for esophageal cancer based on data from
  epidemiologic studies, although ethanol in its
  pure form does not act as a carcinogen in
  experimental models.
• Potential reasons are
• (1)alcohol acts as a solvent for tobacco
  carcinogens or that impurities in alcoholic
  drinks are the carcinogenic agents.
• (2) exposure to high levels of acetaldehyde is
  responsible for the increased cancer risk.
• However, alcohol does not appear to be an
  important risk factor for adenocarcinoma of
  esophagus.

36
Pooled RR for Esophageal Cancer Associated with
Intake of Alcohol
Bagnardi et al., Br J Cancer, 2001
37
Trends in Esophageal Cancer Incidence Rates in 9
SEER Areas in The US by Gender, Race, and Cell
Type from 1973-1975 through 1996-2000
Age standardized to 2000 US population
38
Alcoholic Beverage Use and Risk of SCCE in US Men
by Race

• Black rate19.4 white rate3.6 in 1986
• Subjects - black white men, 30-79
• Cases - 124 white, 249 black
• Controls - 750 white, 614 black ORs adjusted for
  tobacco, diet, income, age, area

Brown et al., JNCI, 1994
39
RR of Esophageal Cancer According to Daily
Consumption of Tobacco and Alcohol
Alcohol Consumption (g ethanol/day) Tobacco Consumption (in g per day) Tobacco Consumption (in g per day) Tobacco Consumption (in g per day)
Alcohol Consumption (g ethanol/day) 0-9 10-19 20
0-40 1.0 3.4 5.1
41-80 7.3 8.4 12.3
81 18.0 19.9 44.4
Number of cases 78 58 308
Tuyns et al, 1977
40
The risk of head and neck cancer associated with
cigarette smoking in never drinkers of alcohol (
left ) and with alcohol drinking in never users
of tobacco ( right ), overall and by study, using
InternationalHead and Neck Cancer Epidemiology
consortium pooled data
Hashibe et al, J Natl Cancer Inst, 2007
41
Cancer of Stomach

• Stomach is exposed directly to ingested ethanol
• Although the concentration of alcohol is diluted
  by gastric juice, it is biological plausible that
  stomach cancer risk could be increased by some
  direct carcinogenic effect of ethanol upon the
  mucosa
• In view of the overall lack of excess risk for
  stomach cancer in the cohort studies, the
  inconsistent results of the case-control studies,
  and the inadequate control for dietary and
  socioeconomic factors, there is little in the
  aggregate data to suggest a causal role for
  drinking of alcoholic beverages in stomach
  cancer.

42
Relative Risks of Alcohol Consumption for Each
Cancer Site
Site Cases Relative risks Relative risks Relative risks
    25 g day 50 g day 100 g day
Oral cavity and pharynx 7,954 1.8 2.9 6.0
Esophagus 7,239 1.5 2.2 4.2
Larynx 3,759 1.4 1.9 4.0
Breast 44,033 1.3 1.7 2.7
Liver 2,294 1.2 1.4 1.9
Colon and rectum 11,296 1.1 1.2 1.4
Stomach 4,518 1.1 1.2 1.3
Ovary 1,651 no association 1.2 1.5
Prostate 4,094 no association 1.1 1.2
Bagnardi et al , British Journal of Cancer 2001
43
Cancer of Liver

• There have been reports over many decades of
  associations between chronic alcohol abuse,
  alcoholic liver cirrhosis and primary liver
  cancer.
• Potential confounding due to hepatitis B virus,
  tobacco smoking and aflatoxin was not explored in
  all the studies whenever it was, it did not
  alter the findings qualitatively. The available
  results, taken together, indicate that drinking
  of alcoholic beverages is causally related to
  liver cancer.

44
Trends in Liver Cancer Incidence Rates in 9 SEER
Areas in The US by Gender and Race from 1973-1975
through 1996-2000
Age standardized to 2000 US population
45
Pooled RR for Liver Cancer Associated with Intake
of Alcohol
Bagnardi et al., Br J Cancer, 2001
46
Cancer of Colorectum

• Although numerous studies reported a positive
  association between alcohol drinking and
  colorectal cancer risk, it remains unclear
  whether alcohol drinking is causally related to
  carcinogenesis of the colorectum
• Since ethanol absorbed efficiently from within
  the stomach and upper intestine, it is unlikely
  that ethanol has direct effect upon the large
  bowel.
• However, some researches suggested alcohol
  consumption behavior may modified the colorectal
  cancer risk
• Colorectal cancer is common in developed
  countries modest increases in risk can have
  important public health implications

47
Trends in colorectal cancer incidence rates in 9
SEER areas in the US by gender and race from
1973-1975 through 1996-2000
Age standardized to 2000 US population
48
Pooled RR for colorectal cancer associated with
intake of alcohol
Moskal et al, 2007
49
Study-specific and Pooled Multivariate Relative
Risks for Colorectal Cancer for Alcohol Intake of
30 g/day or Greater versus 0 g/day.
Cho et al, Annual Int Med, 2004
50
RRs (highest vs. lowest category) for Published
Cohort Studies or Nested Case-Control Studies on
the between Total Alcohol Consumption and Colon
Cancer Incidence.
Moskal et al, IJC, 2007
51
RRs (highest vs. lowest category) for Published
Cohort Studies or Nested Case-Control Studies on
the between Total Alcohol Consumption and Rectal
Cancer Incidence.
Moskal et al, 2007
52
Intake of baseline wine, beer and spirits/liquors
intakes (g/day) and risk of colorectal, colon and
rectal cancer (men and women combined).
Ferrari et al, Int J Cancer, 2007
53
Cancer of Female Breast

• Many epidemiologic studies have identified
  chronic alcohol consumption as a risk factor for
  breast cancer.
• Previous meta-analyses have shown a positive
  association between alcohol intake and breast
  cancer
• 4 of breast cancers in developed countries may
  be attributable to use of alcohol

54
Individual Study Estimates of Crude Odds Ratios
(log scale) ofthe Risk of Breast Cancer
Associated with Drinkers versus Non-Drinkers and
95 CI
Key et al, Cancer Causes and Control, 2006
55
Trends in Breast Cancer Incidence Rates in 9
SEER Areas in the US by Race from 1973-1975
through 1996-2000
Age standardized to 2000 US population
56
Pooled RR for Breast Cancer Associated with
Median Alcohol Intake
Collaborative group on hormonal factors in breast
cancer, Br J Cancer, 2002
57
Cancer of Pancreas

• Most epidemiologic studies have found little or
  no support for a causal relationship between
  light and moderate alcohol use and risk of
  pancreatic cancer

58
Trends in Pancreas Cancer Incidence Rates in 9
SEER Areas in the US by Gender and Race from
1973-1975 through 1996-2000
Age standardized to 2000 US population
59
Pooled RR for Pancreas Cancer Associated with
Intake of Alcohol
Bagnardi et al., Br J Cancer, 2001
60
Alcoholic Beverage Use and risk of pancreas
cancer in US by Race and Gender
Silverman et al., Cancer Res, 1995
61
Cancer of Lung

• There is evidence that alcohol can act as a
  prooxidant in tissues, including lung tissue, and
  on lipids, including lung membrane lipids.
  Alcohol can induce the expression of enzymes that
  are related to carcinogen metabolism, and
  compounds other than ethanol that are contained
  in alcoholic beverages may have carcinogenic
  effects.

62
Alcohol consumption (g/d) and lung cancer by
histologic type pooled multivariate-adjusted
relative risks (RR)
Freudenheim et al, Am J Clin Nutr, 2005
63
Summary of the Studies Included in the
Meta-Analysis
Bagnardi et al., Br J Cancer, 2001
64
Current issues of alcohol and cancer research
65
Current issues of alcohol and cancer research

• Measurement of alcohol drinking
• Personal susceptibility
• Moderate drinking
• Under-age drinking
• Gene/environmental-environmental interaction

66
Estimate of Alcohol Drinking

• NIAAA suggests that the estimates of alcohol
  drinking should prepared taking into account of
• Volume of drinking
• Pattern of drinking

67
What is a Drink?

• Despite the differences in concentration, the
  average intake of ethanol per drink is
  approximately constant across beverage types.
• A standard drink is
• One 12-ounce bottle of beer or wine cooler
• One 5-ounce glass of wine
• 1.5 ounces of 80-proof distilled spirits.

Different beers have different alcohol content.
Malt liquor has a higher alcohol content than
most other brewed beverages. 80-proof 40 ABV
(alcohol by volume)
68
Current Issues of Alcohol and Cancer Research

• Measurement of alcohol drinking
• Personal susceptibility
• Moderate drinking
• Under-age drinking
• Gene/environmental-environmental interaction

69
Alcohol metabolism

• Ethanol is eliminated from the body by oxidation
  to acetaldehyde and then to acetate, reactions
  catalyzed by alcohol dehydrogenase, and ALDH2,
  respectively
• ADH alcohol dehydrogenase
• CYP2E1 Cytochrome p450 2E1
• NQO1NAD(P)Hquinone oxidoreductase 1
• ALDH2 Aldehyde dehydrogenase 2

ADH
ALDH2
Alcohol (R-OH)
Aldehyde (R-CHO)
Acetic acid (R-COOH)
CYP2E1 NQO1
70
ALDH2 in Alcohol Metabolism

• When the individuals with ALDH22 (Lys487 or
  rs671 A) gene drink, the inactive enzyme fails to
  promptly metabolize acetaldehyde, and leads to
  its excessive accumulation after drinking
• The enzyme activity of ALDH2 polymorphisms
• 1-1 70-100
• 1-2 6-20
• 2-2 close to 0
• In ALDH2 2-2 and ALDH2 1-2, blood acetaldehyde
  concentration are approximately 19 and 6 times
  that in ALDH2 1-1, respectively

71
ALDH2 in Alcohol Metabolism

• The Ethanol Metabolic Pathway and the Role of the
  ALDH2 Variants in Acetaldehyde Accumulation

Brooks PJ et al. PLoS Med. 2009 Mar 246(3)e50.
72
Alcohol flushing (Asian glow)

• predominantly due to an inherited deficiency in
  the enzyme ALDH2

Facial flushing in a 22-year-old ALDH2
heterozygote before (left) and after (right)
drinking alcohol. Brooks PJ et al. PLoS Med.
2009 Mar 246(3)e50.
73
Based on 480 College Students in Japan

• After a glass of beer(0.5L)
• ALDH2 1-1
• ALDH2 1-2
• ALDH2 2-2

Takashita et al (1999) on Alcoholisms
74
Alcohol Flushing and Cancer

• A study in Japanese alcoholics showed that the
  amount of mutagenic acetaldehyde-derived DNA
  adducts in white blood cells was significantly
  higher in ALDH2-deficient heterozygotes than in
  individuals with active ALDH2. In this study,
  while the two groups were matched for alcohol
  consumption, the ALDH2-deficient group consumed
  slightly less alcohol on average than the
  controls. (Matsuda et al, Chem Res Toxicol, 2006)
• Also, ALDH2 heterozygotes who drank alcohol had
  higher levels of white blood cells with
  chromosomal damage than drinkers with active
  ALDH2 (Ishikawa et al, Mutat Res , 2007)
• the 2007 IARC Working Group on alcohol and cancer
  specifically noted the above evidences supporting
  a causal role for acetaldehyde in alcohol-related
  esophageal

75
ALDH22 Gene Frequency in Different Populations
Caucasoid Mongoloid
Finns 0 Chinese 0.159
German 0 Chinese (Taiwan) 0.24
Hungarians 0.013 Filipinos 0.006
Native Americans 0 Japanese 0.23-0.46
Siberians (Yakut) 0 Koreans 0.151
Swedes 0 Malays 0.034
Turks 0 Mongolian 0.05
Finns 0 Myanmar 0.02
Thais 0.05
76
ALDH22 Gene Frequency in Different Populations
Negroid Other
African 0 Aurocanians (South Chile) 0
Australian Aborigines 0
Caboclos (Brazil) 0.174
Indians Eskimos (Alaska) 0
North American 0-0.2 Mestizos (Mexico) 0
Northwest coast 0.2 Mexican American 0
Pima Indians 0.044 Papua New Guineans 0.04
South American 0.4 Swedish Lapps 0
77
Current Interests of Alcohol and Cancer Research

• Measurement of alcohol drinking
• Personal susceptibility
• Moderate drinking
• Under-age drinking
• Gene/environmental-environmental interaction

78
ALDH2 Deficiency Increases the Risk of
Alcohol-Related Squamous Cell Esophageal Cancer 

• Case control studies in Japan and Taiwan have
  consistently demonstrated a strong link between
  the risk of esophageal squamous cell carcinoma
  and alcohol consumption in low-activity ALDH2
  heterozygotes, with odds ratios (ORs) ranging
  from 3.7 to 18.1 after adjustment for alcohol
  consumption.
• Most studies show ORs of over 10 for increased
  risk in heterozygotes who are heavy drinkers.
• In the Japanese and Taiwanese studies, a
  strikingly high proportion (5869) of the
  excessive risk for esophageal cancer is
  attributable to drinking by low-activity ALDH2
  heterozygous individuals.

Brooks PJ et al. PLoS Med. 2009 Mar 246(3)e50.
79
Moderate Alcohol Drinking

• Many of these studies have evaluated dose
  response relationships with levels of ethanol
  consumption and the various outcomes of interest.
  U-shape or J-shape were found in alcohol intake
  and several disease incidence.
• Many studies found moderate drinking is the
  only level of drinking that has been shown to
  have potential health benefits, however, the
  level of moderate or heavy have not been
  defined consistently across studies (Gaziano et
  al., 2000 Klatsky, 2002 NIAAA, 1992).
• Further, they are not always consistent with the
  definition of moderate drinking in the USDA/DHHS
  Dietary Guidelines (2000) no more than one drink
  per day for women and no more than two drinks per
  day for men

80
Complication

• individual differences BAC and metabolism
• Intensity frequency- (3 drinks in one hour will
  produce a much higher BAC than 3 drinks over the
  course of 3 hours ), and therefore different
  effect
• Confounding and modification by lifestyle
  variables also could be a factor in the observed
  health differences between drinkers and
  nondrinkers
• Drinking pattern and size is different through
  out countries and occasions
• Also, depend on outcome of interest, co-morbid
  conditions, age, gender, family history, or
  specific health condition.

81
Recommendations

• Government dietary guidelines
• Except for those individuals at particular risk,
  consumption of 2 drinks a day for men and 1 for
  women is unlikely to increase health risks.
• As risks for some conditions and diseases do
  increase at higher levels of consumption, men
  should be cautioned to not exceed 4 drinks on any
  day and women to not exceed 3 on any day
• Note However, moderate alcohol use should
  not be construed as healthy alcohol use.

82
Moderate drinking and cancer

• Low to moderate alcohol consumption(?3 drink/day)
  in women increases the risk of certain cancers
  (oral cavity and pharynx, esophagus, larynx,
  rectum, breast, and liver, and with a decreased
  risk for thyroid cancer, nonHodgkin lymphoma,
  and renal cell carcinoma ). For every additional
  drink regularly consumed per day, the increase
  incidence in developed countries is estimated to
  15 cancers per 1000 women up to age 751.

1 Allen NE et al. Moderate alcohol intake and
cancer incidence in women. J Natl Cancer Inst.
2009 Mar 4101(5)296-305. Epub 2009 Feb 24.
83
Estimated increase in the relative risk (95 CI)
of incident cancer per 10-g/d increase in alcohol
intake (drinkers only). Analyses are adjusted for
age, region of residence, SES, BMI, smoking,
physical activity, use of OC and HRT
Allen NE et al. J Natl Cancer Inst. 2009
84
Relative risk (95 floated confidence interval)
of breast cancer by amount and type of alcohol
consumed (drinkers only). Analyses are adjusted
for age, region of residence, SES, BMI, smoking,
physical activity, use of OCs and HRT. (FCI
floated confidence interval. "Other alcoholic
drinks" is defined as drinkers of beer and/or
spirits exclusively or a mixture of wine, beer,
and/or spirits. )
Allen NE et al. Moderate alcohol intake and
cancer incidence in women. J Natl Cancer Inst.
2009 Mar 4101(5)296-305. Epub 2009 Feb 24.
85
Current Issues of Alcohol and Cancer Research

• Measurement of alcohol drinking
• Personal susceptibility
• Moderate drinking
• Under-age drinking
• Gene/environmental-environmental interaction

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FACT!!

• A 1996 study of children ages 9 to 11 found that
  children were more familiar with Budweisers
  television frogs than Kelloggs Tony the Tiger,
  the Mighty Morphin Power Rangers, or Smokey the
  Bear
• A study of 12-year-olds found that children who
  were more aware of beer advertising held more
  favorable views on drinking and expressed an
  intention to drink more often as adults than did
  children who were less knowledgeable about the
  ads.
• A recent economic analysis assessed the effects
  of alcohol advertising on youth drinking
  behaviors by comparing federally reported levels
  of youth drinking with detailed reports on
  alcohol advertising in local markets during the
  same years. The analysis concluded that a
  complete ban on alcohol advertising could reduce
  monthly levels of youth drinking by 24 and youth
  binge drinking by about 42.
• The Center on Alcohol Marketing and Youth found
  that, in 2001, youth in the United States were 93
  times more likely to see an ad promoting alcohol
  than an industry ad discouraging underage
  drinking. In fact, compared to underage youth,
  adults age 21 and over were more than twice as
  likely to see advertising discouraging underage
  drinking

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Under-Age Drinking and Cancer

• Researchers start to look into the issues
  regarding under age drinking
• So far, very few studies address this on cancer,
  however, some researchers suspected drinking
  alcohol in younger age may associated with early
  onset of certain alcohol-related cancer.

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Current Issues of Alcohol and Cancer Research

• Measurement of alcohol drinking
• Personal susceptibility
• Moderate drinking
• Under-age drinking
• Gene/environmental-environmental interaction

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Conclusion
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IARC evaluation

• Alcoholic beverages are carcinogenic to humans
  group 1 carcinogen (1988, revision 2007).

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IARC

• Group 1 The agent (mixture) is carcinogenic to
  humans. The exposure circumstance entails
  exposures that are carcinogenic to humans
• Group 2
• Group 2A The agent (mixture) is probably
  carcinogenic to humans.The exposure circumstance
  entails exposures that are probably carcinogenic
  to humans.
• Group 2B The agent (mixture) is possibly
  carcinogenic to humans.The exposure circumstance
  entails exposures that are possibly carcinogenic
  to humans.
• Group 3 The agent (mixture or exposure
  circumstance) is not classifiable as to its
  carcinogenicity to humans
• Group 4 The agent (mixture) is probably not
  carcinogenic to humans.

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Questions?