Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk: a meta-analysis.
OBJECTIVE
To evaluate the contribution of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms to the risk of esophageal cancer.


METHODS
Nineteen articles were included by searching MEDLINE, EMBASE and the Chinese Biomedical Database, 13 on ADH1B and 18 on ALDH2. We performed a meta-analysis of case-control studies including 13 studies on ADH1B (cases/controls: 2390/7100) and 18 studies on ALDH2 (2631/6030).


RESULTS
The crude odds ratio [OR (95% confidence interval)] was 2.91 (2.04-4.14) for ADH1B*1/*1 (vs ADH1B*2/*2) and 1.32 (1.17-1.49) for ADH1B*1/*2. The crude OR for ALDH2*1/*2 (vs ALDH2*1/*1) was 2.52 (1.76-3.61). ADH1B*1/*1 increased the risk of esophageal cancer among never/rare [1.56 (0.93-2.61)], moderate [2.71 (1.37-5.35)], and heavy drinkers [3.22 (2.27-4.57)]. ADH1B*1/*2 was associated with a modest risk among moderate drinkers [1.43 (1.09-1.87)]. ALDH2*1/*2 increased the risk among never/rare [1.28 (0.91-1.80)], moderate [3.12 (1.95-5.01)], and heavy [7.12 (4.67-10.86)] drinkers, and among ex-drinkers [5.64 (1.57-20.25)]. ALDH2*2/*2 increased the risk among drinkers [4.42 (1.72-11.36)]. ADH1B*1/*1 plus ALDH2*1/*2 was associated with the highest risk for heavy drinkers [12.45 (2.9-53.46)]. The results of the meta-regression analysis showed that the effects of ADH1B*1/*1 and ALDH2*1/*2 increased with the level of alcohol consumption. ALDH2*1/*2 was associated with a high risk among Taiwan Chinese and Japanese drinkers, as opposed to a moderate risk among drinkers in high-incidence regions of Mainland China. ADH1B*1/*1 in heavy drinkers and ALDH2*1/*2 in moderate-to-heavy drinkers was associated with similarly high risk among both men and women.


CONCLUSIONS
ADH1B/ALDH2 genotypes affect the risk of esophageal cancer, and the risk is modified by alcohol consumption, ethnicity, and gender.
Yang
Shu-Juan
SJ
Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu 610041, Sichuan Province, China.
Yokoyama
Akira
A
Yokoyama
Tetsuji
T
Huang
Yu-Chuan
YC
Wu
Si-Ying
SY
Shao
Ying
Y
Niu
Jin
J
Wang
Jie
J
Liu
Yu
Y
Zhou
Xiao-Qiao
XQ
Yang
Chun-Xia
CX
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan / Q000208:ethnology; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012727:Sex Characteristics; D013624:Taiwan / Q000208:ethnology
C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial
Alcohol Clin Exp Res. 2004 Jan;28(1):10-4
14745297
Biochemistry. 1984 Nov 20;23(24):5847-53
6395883
Asian Pac J Cancer Prev. 2005 Jul-Sep;6(3):256-62
16235983
Cancer Epidemiol Biomarkers Prev. 1996 Feb;5(2):99-102
8850269
Cancer Epidemiol Biomarkers Prev. 2002 Sep;11(9):895-900
12223435
World J Gastroenterol. 2007 Nov 21;13(43):5760-4
17963305
Clin Chem Lab Med. 2008;46(3):323-8
18254707
Am J Hum Genet. 1999 Sep;65(3):795-807
10441588
J Clin Gastroenterol. 1997 Dec;25(4):568-75
9451664
Alcohol Clin Exp Res. 2004 Aug;28(8 Suppl Proceedings):117S-122S
15318097
Lancet. 1994 Mar 19;343(8899):741-2
7907720
Lancet Oncol. 2007 Apr;8(4):292-3
17431955
Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):696-703
16614111
Biochem Genet. 2005 Jun;43(5-6):223-7
16144299
Int J Cancer. 2007 Sep 1;121(5):1047-54
17471563
Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1967-71
16103445
Alcohol. 2005 Apr;35(3):175-85
16054979
Lancet Oncol. 2009 Nov;10(11):1033-4
19891056
Cancer Lett. 2002 Dec 5;186(2):193-9
12213289
Psychol Bull. 2006 Jul;132(4):607-21
16822169
Int J Cancer. 2007 Sep 1;121(5):1132-7
17487833
CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
15761078
Lancet. 1981 Oct 31;2(8253):982
6117742
World J Gastroenterol. 2008 Mar 7;14(9):1444-9
18322963
Carcinogenesis. 2002 Nov;23(11):1851-9
12419833
World J Gastroenterol. 2009 May 21;15(19):2395-400
19452585
J Clin Invest. 1989 Jan;83(1):314-6
2562960
Am J Psychiatry. 1995 Aug;152(8):1219-21
7625477
Cancer Sci. 2006 Sep;97(9):905-11
16805853
Int J Cancer. 2008 Mar 15;122(6):1347-56
18033686
Am J Gastroenterol. 2000 Oct;95(10):2958-64
11051375
Alcohol Clin Exp Res. 2006 Mar;30(3):491-500
16499490
Carcinogenesis. 2001 Jun;22(6):913-6
11375898
Carcinogenesis. 2001 Mar;22(3):433-9
11238183
Cancer. 2006 Jun 1;106(11):2345-54
16639733
Cancer Causes Control. 2010 Feb;21(2):269-74
19866363
Int J Mol Med. 2003 Aug;12(2):169-74
12851712
Br J Cancer. 2001 Nov 30;85(11):1700-5
11742491