Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles.
BACKGROUND
Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis.


OBJECTIVE
To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors. Methods A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed.


RESULTS
Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10(-40) and OR=4.13, p=8.4×10(-76), respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk.


CONCLUSIONS
Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.
Tanaka
Fumiaki
F
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Yamamoto
Ken
K
Suzuki
Sadao
S
Inoue
Hiroshi
H
Tsurumaru
Masahiko
M
Kajiyama
Yoshiaki
Y
Kato
Hoichi
H
Igaki
Hiroyasu
H
Furuta
Koh
K
Fujita
Hiromasa
H
Tanaka
Toshiaki
T
Tanaka
Yoichi
Y
Kawashima
Yoshiyuki
Y
Natsugoe
Shoji
S
Setoyama
Tetsuro
T
Tokudome
Shinkan
S
Mimori
Koshi
K
Haraguchi
Naotsugu
N
Ishii
Hideshi
H
Mori
Masaki
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D003043:Cocarcinogenesis; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology
D009363:Neoplasm Proteins; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial