Association of aldehyde dehydrogenase 2 gene polymorphism with pancreatic cancer but not colon cancer

Miyasaka, Kyoko; Hosoya, Hiroko; Tanaka, Yasuo; Uegaki, Satoko; Kino, Kenji; Shimokata, Hiroshi; Kawanami, Takako; Funakoshi, Akihiro

doi:10.1111/j.1447-0594.2010.00616.x

Cited by 17 publications

(17 citation statements)

References 39 publications

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“…Finally, eleven studies met the inclusion criteria (comprising 2909 cases and 4903 controls). Genotype distributions in the controls of Chiang's study[15] and Miyasaka's syudy[16] were not in agreement with the HWE. The detailed characteristics of the studies are shown in Table 1.…”

Section: Resultsmentioning

confidence: 75%

“…Therefore, further studies are warranted in other high risk areas. Fourthly, although the genotype distributions in the pooled controls from the included studies were in agree with HWE, genotype distributions in the controls from Chiang's study[15] and Miyasaka's study[16] were not in agreement with HWE, therefore, the results may be biased. Lastly, publication bias may have occurred, although the funnel plot did not indicate this; negative findings were likely to be unreported.…”

Section: Discussionmentioning

confidence: 91%

“…Several case-control studies have been conducted to clarify the association between this polymorphism and risk of colorectal cancer risk [15]–[25]; however, the results are inconsistent. Chiang's study [15] found that the allele frequency of ALDH2 A was significantly higher in colorectal cancer cases; however, Miyasaka's study[16] found that the A/A genotype of ALDH2 might not be a risk factor for colorectal cancer. Yang's study [17] found that the ALDH2 A/A genotype could increase susceptibility to CRC (adjusted OR = 1.86 (95% CI, 1.12–3.09)); however, Yin's study [19] discovered that the ALDH2A/A genotype was related to a statistically significantly decreased risk of colorectal cancer (adjusted OR 0.55, 95% CI = 0.33–0.93).…”

Section: Introductionmentioning

confidence: 93%

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Meta-Analysis of the Aldehyde Dehydrogenases-2 (ALDH2) Glu487Lys Polymorphism and Colorectal Cancer Risk

et al. 2014

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A number of studies have explored the association of the aldehyde dehydrogenases-2 (ALDH2) Glu487Lys polymorphism and risk of colorectal cancer; however, the results are inconsistent. We performed this meta-analysis to clarify this issue using all the available evidence. Relevant studies were retrieved by searching PubMed. Eleven case-control studies were included in the meta-analysis, representing 2909 cases and 4903 controls. The pooled results based on all included studies showed a decreased colorectal cancer risk in the analysis of the GA genotype vs. the GG genotype (OR = 0.81, 95%CI = 0.68–0.98, p = 0.03) and in the dominant genetic model analysis (OR = 0.81, 95%CI = 0.67–0.98, p = 0.03). However, there was no statistical difference in the AA vs. GG analysis (OR = 0.74, 95%CI = 0.52–1.06,p = 0.11) and the recessive genetic model analysis (OR = 0.86, 95%CI = 0.69–1.07, p = 0.17). Cumulative meta-analysis based on publication time confirmed these findings. Patients with colorectal cancer had a higher frequency of the GG genotype (OR = 1.10, 95% CI = 1.02–1.20, p = 0.02) and a lower frequency of the GA genotype (OR = 0.89, 95%CI = 0.81–0.98, p = 0.02) comparing with control population. Our results suggested that the ALDH2 Glu487Lys polymorphism may be associated with a decreased risk of colorectal cancer.

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Section: Resultsmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 93%

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Meta-Analysis of the Aldehyde Dehydrogenases-2 (ALDH2) Glu487Lys Polymorphism and Colorectal Cancer Risk

et al. 2014

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“…No association between liver cancer and ALDH2*2 alone was initially reported (68); however, a risk may be associated with hepatitis C infection (75). Conflicting results have also been found for colon cancer (76, 77). …”

Section: Impact On Human Healthmentioning

confidence: 96%

A Personalized Medicine Approach for Asian Americans with the Aldehyde Dehydrogenase 2*2 Variant

Gross

Zambelli²,

Small³

et al. 2015

Annu. Rev. Pharmacol. Toxicol.

117

122

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Asian Americans are one of the fastest-growing populations in the United States. A relatively large subset of this population carries a unique loss-of-function point mutation in aldehyde dehydrogenase 2 (ALDH2), ALDH2*2. Found in approximately 560 million people of East Asian descent, ALDH2*2 reduces enzymatic activity by approximately 60% to 80% in heterozygotes. Furthermore, this variant is associated with a higher risk for several diseases affecting many organ systems, including a particularly high incidence relative to the general population of esophageal cancer, myocardial infarction, and osteoporosis. In this review, we discuss the pathophysiology associated with the ALDH2*2 variant, describe why this variant needs to be considered when selecting drug treatments, and suggest a personalized medicine approach for Asian American carriers of this variant. We also discuss future clinical and translational perspectives regarding ALDH2*2 research.

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“…Matsuo et al reported that high level of alcohol consumption was associated with an increased rectal cancer risk but not colon cancer risk among individuals with ALDH2*1/*2 [46]. Miyasaka et al found no association between ALDH2*2 and colon cancer and did not assess the interaction between ALDH2*2 and alcohol drinking on colon cancer risk [47]. Overall, the role of ALDH2*2 in the development of colorectal cancer is inconclusive and all of the studies conducted to date have a small sample size that resulted in insufficient statistical power and lack of precision.…”

Section: Aldh2 Polymorphism and Risk Of Alcohol-related Cancersmentioning

confidence: 99%

ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective

2017

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The occurrence of more than 200 diseases, including cancer, can be attributed to alcohol drinking. The global cancer deaths attributed to alcohol-consumption rose from 243,000 in 1990 to 337,400 in 2010. In 2010, cancer deaths due to alcohol consumption accounted for 4.2% of all cancer deaths. Strong epidemiological evidence has established the causal role of alcohol in the development of various cancers, including esophageal cancer, head and neck cancer, liver cancer, breast cancer, and colorectal cancer. The evidence for the association between alcohol and other cancers is inconclusive. Because of the high prevalence of ALDH2*2 allele among East Asian populations, East Asians may be more susceptible to the carcinogenic effect of alcohol, with most evidence coming from studies of esophageal cancer and head and neck cancer, while data for other cancers are more limited. The high prevalence of ALDH2*2 allele in East Asian populations may have important public health implications and may be utilized to reduce the occurrence of alcohol-related cancers among East Asians, including: 1) Identification of individuals at high risk of developing alcohol-related cancers by screening for ALDH2 polymorphism; 2) Incorporation of ALDH2 polymorphism screening into behavioral intervention program for promoting alcohol abstinence or reducing alcohol consumption; 3) Using ALDH2 polymorphism as a prognostic indicator for alcohol-related cancers; 4) Targeting ALDH2 for chemoprevention; and 5) Setting guidelines for alcohol consumption among ALDH2 deficient individuals. Future studies should evaluate whether these strategies are effective for preventing the occurrence of alcohol-related cancers.

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Association of aldehyde dehydrogenase 2 gene polymorphism with pancreatic cancer but not colon cancer

Cited by 17 publications

References 39 publications

Meta-Analysis of the Aldehyde Dehydrogenases-2 (ALDH2) Glu487Lys Polymorphism and Colorectal Cancer Risk

Meta-Analysis of the Aldehyde Dehydrogenases-2 (ALDH2) Glu487Lys Polymorphism and Colorectal Cancer Risk

A Personalized Medicine Approach for Asian Americans with the Aldehyde Dehydrogenase 2*2 Variant

ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective

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