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Alcohol Metabolism and Its Implications for Cancer

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Alcohol and Cancer

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Abstract

As described in Chap. 1, alcohol has been classified as carcinogenic to humans at several sites in the body by the International Agency for Research on Cancer (Secretan et al. 2009). These include the upper aero-digestive tract (UADT), liver, colon/rectum, and female breast. Numerous mechanisms have been proposed for these multiple carcinogenic effects (Zakhari 2006). In this chapter, we discuss some of the diverse mechanisms involving alcohol metabolism or alcohol-induced changes in metabolic pathways (Fig. 4.1) that may lead to cancer. These include formation of acetaldehyde, changes in the NADH/NAD+ ratio, increases in oxidative stress, induction of cytochrome P450-2E1 (CYP2E1), procarcinogen activation, changes in folate and methionine metabolism, and effects on retinoid metabolism.

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Abbreviations

ADH:

Alcohol dehydrogenase

ALDH:

Aldehyde dehydrogenase

BAL:

Blood alcohol level

BHMT:

Betaine homocysteine methyltransferase

CβS:

Cystathionine β-synthase

CrPdG:

Crotonaldehyde-derived N 2-propanodeoxyguanosine adduct

CtBP:

C-terminal-binding protein

CTH:

Cystathionine hydrolase

CYP2E1:

Cytochrome P450-2E1

DNMT:

DNA methyl transferase

GSH:

Glutathione

hMLH1:

Human MutL homolog 1, colon cancer

HNE:

4-hydroxynonenal

JNK:

JUN N-terminal kinase

MAT:

Methionine adenosyltransferase

MDA:

Malondialdehyde

MEOS:

Microsomal ethanol-oxidizing system

MS:

Methionine synthase

MTHFR:

5,10 Methylenetetrahydrofolate reductase

N 2-Et-dG:

N 2-Ethyl-2-deoxyguanosine

N 2-Etl-dG:

N 2-Ethylidene-2-deoxyguanosine

NFκB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

MAP kinase:

Mitogen-activated protein kinase

RA:

Retinoic acid

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SAH:

S-adenosylhomocysteine

SAM:

S-adenosylmethionine

SHMT:

Serine hydroxymethyltransferase

SIR:

Silent information regulator

SRC:

Src tyrosine kinase

THF:

Tetrahydrofolate

UADT:

Upper aero-digestive tract

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  1. Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA

    Gary J. Murray PhD, Philip J. Brooks PhD & Samir Zakhari PhD

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  1. Gary J. Murray PhD
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  2. Philip J. Brooks PhD
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  1. , Division of Metabolism and Health Effect, National Institute on Alcohol Abuse and, 5635 Fishers Lane, Room 2031, Bethesda, 20892-9304, Maryland, USA

    Samir Zakhari

  2. , Deparment of Pharmaceutical Sciences, University of Colorado Denver, 12700 East 19th Ave, Aurora, 80045, Colorado, USA

    Vasilis Vasiliou

  3. , Division of Metabolism and Health Effect, National Institute on Alcohol Abuse and, 5635 Fishers Lane, Room 2031, Bethesda, 20892-9304, Maryland, USA

    Q. Max Guo

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Murray, G.J., Brooks, P.J., Zakhari, S. (2011). Alcohol Metabolism and Its Implications for Cancer. In: Zakhari, S., Vasiliou, V., Guo, Q. (eds) Alcohol and Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0040-0_4

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