Difference between revisions of "Team:TAS Taipei"
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| − | <html | + | <html><head> |
| − | + | <title>TAS_Taipei</title> | |
| − | <head> | + | <!--Personal--> |
| − | + | <style> | |
| − | + | html, body { | |
| − | + | margin: 0; | |
| − | + | font-family: 'Nexa light', sans-serif; | |
| − | + | font-size: 16px; | |
| − | + | background-color: #FFFFFF; | |
| − | + | ||
| − | <style | + | |
| − | + | ||
| − | body { | + | |
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} | } | ||
| − | + | * { | |
| − | + | box-sizing: border-box; | |
} | } | ||
| − | . | + | .toolbar { |
| − | width: | + | min-height: 64px; |
| + | max-height: 64px; | ||
| + | width: 100%; | ||
| + | background-color: whitesmoke; | ||
| + | position: fixed; | ||
| + | z-index: 2; | ||
} | } | ||
| − | . | + | .spacer { |
| − | width: | + | width: 100%; |
| + | height: 64px; | ||
} | } | ||
| − | . | + | |
| − | width: | + | .nav-tab { |
| + | position: static !important; | ||
| + | display:inline-block; | ||
| + | min-height: 53px; | ||
| + | max-height: 53px; | ||
| + | line-height: 48px; | ||
| + | width: 9.8%; | ||
| + | text-align: center; | ||
| + | color: black; | ||
| + | text-decoration: none; | ||
| + | font-size: 1vw; | ||
| + | margin-top: 1vh; | ||
} | } | ||
| − | + | ||
| − | + | .nav-tab-special { | |
| − | + | position: static !important; | |
| − | . | + | display:inline-block; |
| − | + | min-height: 64px; | |
| − | + | max-height: 64px; | |
| − | + | line-height: 64px; | |
| − | + | width: 15%; | |
| − | + | text-align: center; | |
| − | + | color: black !important; | |
| − | + | text-decoration: none; | |
| − | + | font-weight: bold; | |
| − | + | font-size: 32px; | |
| − | + | font-size: 1vw; | |
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} | } | ||
| − | . | + | |
| − | left: | + | .content { |
| + | margin-left: 240px; | ||
| + | z-index: 1; | ||
} | } | ||
| − | . | + | |
| + | .sidenav { | ||
| + | height: 100%; | ||
| + | width: 18%; | ||
| + | position: fixed; | ||
| + | z-index: 1; | ||
| + | top: 0; | ||
left: 0; | left: 0; | ||
| + | background-color: azure; | ||
| + | overflow-x: hidden; | ||
| + | padding-top: 20px; | ||
} | } | ||
| − | . | + | |
| − | + | .sidenav div { | |
| + | padding: 8px 6px 8px 16px; | ||
| + | text-decoration: none; | ||
| + | font-size: 0.9em !important; | ||
| + | color: #000000; | ||
| + | display: block; | ||
} | } | ||
| − | . | + | .subnavdiv { |
| − | margin-left: | + | padding: 8px 6px 8px 16px !important; |
| + | margin-left: 20px !important; | ||
| + | font-size: 0.7em !important; | ||
} | } | ||
| − | . | + | .thirdsubnavdiv { |
| − | margin-left: | + | padding: 8px 6px 8px 16px !important; |
| + | margin-left: 40px !important; | ||
| + | font-size: 0.5em !important; | ||
} | } | ||
| − | . | + | |
| − | + | .sidenav div:hover { | |
| + | color: #808080; | ||
| + | cursor: pointer; | ||
} | } | ||
| − | + | ||
| − | + | @media screen and (max-height: 450px) { | |
| + | .sidenav {padding-top: 15px;} | ||
| + | .sidenav a {font-size: 18px;} | ||
} | } | ||
| − | . | + | |
| − | + | .slideshow-image { | |
| + | width: 100%; | ||
| + | max-height: 900px; | ||
} | } | ||
| − | . | + | |
| − | + | .hidden-image { | |
| + | display: none; | ||
} | } | ||
| − | . | + | |
| − | + | .paragraph { | |
| + | min-height: 45%; | ||
} | } | ||
| − | . | + | |
| − | + | .splash{ | |
| + | position: relative; | ||
| + | z-index: 1; top: 64px; width: 100%; | ||
} | } | ||
| − | + | ||
| − | + | .splash-image { | |
| − | + | ||
| − | . | + | |
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width: 100%; | width: 100%; | ||
} | } | ||
| − | . | + | .splash h1 { |
| − | + | position: absolute; | |
| − | + | bottom: 40%; | |
| − | + | color: white; | |
| − | + | text-shadow: 0px 10px 30px black; | |
| − | + | font-size: 5em; | |
| − | + | left: 0; | |
| − | + | ||
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| − | text- | + | |
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right: 0; | right: 0; | ||
} | } | ||
| − | + | #content { | |
| − | + | position: absolute; | |
| − | + | width: 100vw; | |
| − | + | height: 100vh; | |
| − | + | top: 8px !important; | |
| − | + | ||
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left: 0; | left: 0; | ||
| + | padding: 0; | ||
| + | margin: /*auto;*/ 0; | ||
} | } | ||
| − | + | #main { | |
| − | margin-left: | + | background-color: #FFFFFF; |
| + | /*margin: auto; | ||
| + | padding: 40px; | ||
| + | margin-left: 15vw;*/ | ||
} | } | ||
| − | . | + | .center-image { |
| − | + | display: block; | |
| + | width: 50%; | ||
| + | position: relative; | ||
} | } | ||
| − | . | + | |
| − | + | .detail-text { | |
| + | padding-top: 0px !important; | ||
| + | padding-left: 32px; | ||
| + | padding-bottom: 0px !important; | ||
| + | font-size: 1em !important; | ||
| + | max-width: 80%; | ||
| + | padding: 32px; | ||
| + | text-align: justify; | ||
| + | line-height: 1.5; | ||
| + | text-justify: inter-word; | ||
} | } | ||
| − | . | + | |
| − | + | .detail-text b { | |
| + | font-weight: 600 !important; | ||
} | } | ||
| − | + | ||
| − | + | h2 { | |
| + | font-size: 2em !important; | ||
| + | font-weight: 900 !important; | ||
| + | } | ||
| + | |||
| + | h3 { | ||
| + | font-size: 1.5em !important; | ||
| + | font-weight: 800 !important; | ||
} | } | ||
| − | + | ||
| − | + | h5 { | |
| + | font-size: 1.25em !important; | ||
| + | font-weight: 700 !important; | ||
} | } | ||
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| − | + | .t1:hover { | |
| − | + | background-image: -webkit-linear-gradient(bottom, #C0392B 10%, #C0392B 90%); | |
| − | + | color: white !important; | |
} | } | ||
| − | . | + | |
| − | + | .t2:hover { | |
| + | background-image: -webkit-linear-gradient(bottom, #DC7633 10%, #DC7633 90%); | ||
| + | color: white !important; | ||
} | } | ||
| − | . | + | |
| − | + | .t3:hover { | |
| + | background-image: -webkit-linear-gradient(bottom, #D4AC0D 10%, #D4AC0D 90%); | ||
| + | color: white !important; | ||
} | } | ||
| − | . | + | |
| − | + | .t4:hover { | |
| + | background-image: -webkit-linear-gradient(bottom, #F7DC6F 10%, #F7DC6F 90%); | ||
| + | color: white !important; | ||
} | } | ||
| − | . | + | |
| − | + | .t5:hover { | |
| + | background-image: -webkit-linear-gradient(bottom, #27AE60 10%, #27AE60 90%); | ||
| + | color: white !important; | ||
} | } | ||
| − | . | + | |
| − | + | .t6:hover { | |
| + | background-image: -webkit-linear-gradient(bottom, #3498DB 10%, #3498DB 90%); | ||
| + | color: white !important; | ||
} | } | ||
| − | . | + | .t7:hover { |
| − | + | background-image: -webkit-linear-gradient(bottom, #A569BD 10%, #A569BD 90%); | |
| + | color: white !important; | ||
} | } | ||
| − | . | + | |
| − | + | .t8:hover { | |
| + | background-image: -webkit-linear-gradient(bottom, #884EA0 10%, #884EA0 90%); | ||
| + | color: white !important; | ||
} | } | ||
| − | . | + | |
| − | + | .t1 { | |
| + | background-image: -webkit-linear-gradient(bottom, #C0392B 10%, whitesmoke 0%); | ||
} | } | ||
| − | . | + | |
| − | + | .t2 { | |
| − | + | background-image: -webkit-linear-gradient(bottom, #DC7633 10%, whitesmoke 0%); | |
} | } | ||
| − | . | + | |
| − | + | .t3 { | |
| + | background-image: -webkit-linear-gradient(bottom, #D4AC0D 10%, whitesmoke 0%); | ||
} | } | ||
| − | . | + | |
| − | + | .t4 { | |
| + | background-image: -webkit-linear-gradient(bottom, #F7DC6F 10%, whitesmoke 0%); | ||
} | } | ||
| − | . | + | |
| − | + | .t5 { | |
| + | background-image: -webkit-linear-gradient(bottom, #27AE60 10%, whitesmoke 0%); | ||
| + | } | ||
| + | |||
| + | .t6 { | ||
| + | background-image: -webkit-linear-gradient(bottom, #3498DB 10%, whitesmoke 0%); | ||
} | } | ||
| − | . | + | |
| − | + | .t7 { | |
| + | background-image: -webkit-linear-gradient(bottom, #A569BD 10%, whitesmoke 0%); | ||
} | } | ||
| − | . | + | |
| − | + | .t8 { | |
| + | background-image: -webkit-linear-gradient(bottom, #884EA0 10%, whitesmoke 0%); | ||
} | } | ||
| − | + | ||
| − | + | section { | |
| + | margin-left: 40px; | ||
} | } | ||
| − | . | + | |
| − | + | .image-card { | |
| + | display: inline-block !important; | ||
| + | background-color: white; | ||
| + | box-shadow: 5px 5px 5px 5px rgba(0, 0, 0, 0.5); | ||
| + | display: inline-block !important; | ||
| + | height: auto; | ||
| + | width: auto; | ||
| + | vertical-align: middle; | ||
| + | margin-left: 20%; | ||
| + | max-width: 40%; | ||
| + | max-height: 40%; | ||
| + | padding: 5px; | ||
} | } | ||
| − | . | + | |
| − | + | .image-card img { | |
| + | width: 100%; | ||
| + | height: 100%; | ||
} | } | ||
| − | . | + | |
| − | + | .image-card p { | |
| + | text-align: justify; | ||
| + | text-justify: inter-word; | ||
| + | font-size: 12px; | ||
| + | padding: 10px; | ||
} | } | ||
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| − | + | .row::after { | |
| − | . | + | content: ""; |
| + | clear: both; | ||
| + | display: table; | ||
width: 100%; | width: 100%; | ||
} | } | ||
| − | + | </style> | |
| − | + | <script> | |
| − | + | function doScrolling(elementY, duration) { | |
| − | + | var startingY = window.pageYOffset; | |
| − | + | var diff = elementY - startingY; | |
| − | + | var start; | |
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| + | <div style="font-weight: bold;" id="sec0Button" onclick="return handleClick(event);">WHAT IS ALDH2 DEFICIENCY?</div><div style="font-weight: bold;" id="sec1Button" onclick="return handleClick(event);">HEALTH CONCERNS & RISKS</div><div style="font-weight: bold;" id="sec2Button" onclick="return handleClick(event);">CURRENT SOLUTIONS</div><div style="font-weight: bold;" id="sec3Button" onclick="return handleClick(event);">OUR GOAL</div><div style="font-weight: bold;" id="sec4Button" onclick="return handleClick(event);">REFERENCES</div></div> | ||
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| + | <h1 style="text-align:center">PROJECT BACKGROUND</h1> | ||
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| + | <section id="sec0Content"><h2>WHAT IS ALDH2 DEFICIENCY?</h2><p class="detail-text">ALDH2 deficiency, more commonly known as Alcohol Flushing Syndrome or Asian Glow, is a genetic condition which interferes with the metabolism of alcohol (Figure 1-1). Normally, ethanol is first converted to acetaldehyde (a toxic intermediate) by the enzyme alcohol dehydrogenase (ADH). Then, acetaldehyde is converted to acetate by the enzyme aldehyde dehydrogenase 2 (ALDH2), which is then safely metabolized in the body. People with ALDH2 deficiency, however, have a point mutation in the gene, which produces a less efficient ALDH2 (mutant: ALDH2*2) by lowering the binding affinity to its coenzyme NAD+ (Larson <i>et al.</i>, 2005; Farrés <i>et al.</i>, 1994). The enzymatic activity in individuals who are deficient can be as low as 4% compared to normal ALDH2 (wild type: ALDH2*1) activity (Chen <i>et al.</i>, 2014; Zhou & Weiner, 2000; Farrés <i>et al.</i>, 1994). As a result, acetaldehyde accumulates and induces an inflammatory reaction that causes the skin to flush or appear red after drinking alcohol (Ijiri, 1999). Facial flushing is the most obvious result of ALDH2 deficiency, but symptoms also include “headaches, nausea, dizziness, and cardiac palpitations after consumption of alcoholic beverages” (Chen <i>et al.</i>, 2014).</p><div class="image-card"><img src="https://static.igem.org/mediawiki/2018/6/6e/T--TAS_Taipei--DoublePathway.gif" class="center-image"><p><b>Figure 1-1: Acetaldehyde accumulates in ALDH2 deficient individuals.</b> Ethanol is first converted to a toxic intermediate, acetaldehyde, by alcohol dehydrogenase (ADH). For individuals with wild type ALDH2, acetaldehyde is converted to acetate by ALDH2*1. However, people who are ALDH2 deficient carry the mutant ALDH2*2, which cannot fully convert acetaldehyde into acetate, and acetaldehyde accumulates as a result. (Figure: Caroline C)</p></div><div style="height: 15px;"></div><p class="detail-text">ALDH2 deficiency affects 540 million people--8% of the world population. In East Asia (which includes Japan, China, and Korea), this is a much bigger problem, where the number rises to 36% (Brooks <i>et al.</i>, 2009). In our home, Taiwan, approximately 47% of the population carries this genetic mutation--the highest ALDH2 deficient percentage in the world (Chang <i>et al.</i>, 2017).</p></section><section id="sec1Content"><h2>HEALTH CONCERNS & RISKS</h2><p class="detail-text">One of the biggest problems of ALDH2 deficiency is that while people recognize that flushing occurs, they are not aware that it is actually dangerous. According to our survey, which sampled close to 700 people around Taipei, many people misunderstood the causes and effects of alcohol flushing. For example, many people thought that turning red is the result of low alcohol tolerance, healthy liver functions, and fast metabolism--this is the opposite of the truth! These findings suggest a need for more public awareness about the health implications of ALDH2 deficiency. (To see our survey results, click <a href="’https://static.igem.org/mediawiki/2018/b/b3/T--TAS_Taipei--SurveyResults.pdf’">here</a>)</p><p class="detail-text">Turning red after consuming alcohol may seem like a mere social inconvenience. Yet, behind this red complexion lies a far more serious problem. The <b>International Agency for Research on Cancer classifies acetaldehyde associated with alcohol consumption as a Group 1 carcinogen</b> (IARC, n.d.). Alcohol and acetaldehyde have been shown to reduce thymidine incorporation into DNA, interfering with DNA synthesis (Dreosti <i>et al.</i>, 1981; Seitz & Stickel, 2010). In other studies with human lymphocyte cells, acetaldehyde increased chromosome damage or the frequency of sister-chromatid exchanges (Obe <i>et al.</i>, 1986; Helander & Lindahl-Kiessling, 1991; Maffei <i>et al.</i>, 2002). When rats were exposed to acetaldehyde, inhalation led to abnormal changes in the nasal mucous membrane, such as degeneration of the tissue, increased cell proliferation, and the development of carcinomas (Woutersen <i>et al.</i>, 1986).</p><div class="image-card"><img src="https://static.igem.org/mediawiki/2018/6/60/T--TAS_Taipei--EthanolQt.jpg" class="center-image"><p><b>Figure 1-2: There are 14 grams of ethanol in each serving of alcohol,</b> which is around 148 mL of wine, 355 mL of beer, and 44 mL of spirit such as whiskey or tequila (NIAAA, n.d). (Figure: Caroline C)</p></div><div style="height: 15px;"></div><p class="detail-text">Acetaldehyde levels over 50 μM are considered toxic and cause mutations in DNA (Yamaguchi <i>et al.</i>, 2012; Kocaelli <i>et al.</i>, 2014). In human studies where roughly 2 to 3 servings of alcohol (0.5-0.6 g alcohol/kg body weight) were ingested (Figure 1-2), salivary acetaldehyde levels in some individuals increased to over 100 μM (Homann <i>et al.</i>, 1997a; Yokoyama <i>et al.</i>, 2008), compared to normal levels of <20 μM without drinking (Lachenmeier & Monakhova, 2011). For people who carry normal, functional ALDH2*1, acetaldehyde can quickly get broken down (Figure 1-3).</p><div class="image-card"><img src="https://static.igem.org/mediawiki/2018/e/ec/T--TAS_Taipei--Acetaldehyde.jpg" class="center-image"><p><b>Figure 1-3: Salivary acetaldehyde levels are much higher in heterozygous (ALDH2*1/*2) individuals, compared to homozygous wild type (ALDH2*1/*1) individuals.</b> Acetaldehyde levels were recorded after drinking 0.6 g ethanol/kg body weight. Salivary acetaldehyde levels are also significantly higher than blood acetaldehyde after drinking (Figure from Yokoyama <i>et al.</i>, 2008).</p></div><div style="height: 15px;"></div><p class="detail-text">For those who are ALDH2 deficient <b>and</b> drink, however, acetaldehyde can accumulate to toxic levels. The strongest effects are seen in the mouth. Studies show that after alcohol consumption, salivary acetaldehyde levels are significantly higher than blood acetaldehyde levels (Stornetta <i>et al.</i>, 2018; Yokoyama <i>et al.</i>, 2008) (Figure 1-3). Since there are other aldehyde dehydrogenases (such as ALDH1A1; Ueshima <i>et al.</i>, 1993) throughout the body that can help metabolize acetaldehyde, blood acetaldehyde concentrations remain relatively low. Most importantly, ALDH2 levels are much higher in the liver, which can break down most acetaldehyde before it enters the bloodstream (Oyama <i>et al.</i>, 2005). Maybe because of this, ALDH2 deficiency does not seem to be directly associated with the development of liver, breast, colorectal, or other common alcohol-related cancers (Väkeväinen <i>et al.</i>, 2000; Chang <i>et al.</i>, 2017).</p><p class="detail-text">These results could also explain why the effects of ALDH2 deficiency are mainly localized rather than widespread throughout the body. <b>Heightened salivary acetaldehyde levels increase the risks of developing esophageal and head and neck cancers.</b> <i>In vivo</i> studies with rats have shown that acetaldehyde administered orally has a tumor-promoting effect (abnormally fast cell growth and division) on the upper respiratory-digestive tract (Homann <i>et al.</i>, 1997b). Depending on how much alcohol is consumed, <b>people with ALDH2 deficiency are two to eight times more likely to develop head and neck cancers </b> (which includes oral cancer, pharyngeal cancer, laryngeal cancer, etc.), and <b>two to twelve times more likely to develop esophageal cancer</b> compared to people with normal ALDH2*1 (Chao <i>et al.</i>, 2000; Yang <i>et al.</i>, 2007; Yokoyama, 2001; Matsuo <i>et al.</i>, 2001; Cui <i>et al.</i>, 2009; Lee <i>et al.</i>, 2007; Wu <i>et al.</i>, 2013; Huang <i>et al.</i>, 2017; Hiraki <i>et al.</i>, 2007).</p></section><section id="sec2Content"><h2>CURRENT SOLUTIONS</h2><p class="detail-text">Today, the solutions for treating flushing include simply using cosmetics to conceal the flushing, or using antihistamines to prevent the release of histamines, which leads to the resulting redness (Chrostek <i>et al.</i>, 2007; Miller <i>et al.</i>, 1998; Quertemont <i>et al.</i>, 2006; Eriksson, 2001). These solutions, however, do not actually address the buildup of acetaldehyde, the main contributor to increased esophageal and head and neck cancers (Sunset, n.d.; Essential AD2, n.d.). On the contrary, these options may actually increase health risks, as they cover up the visible symptoms without reducing acetaldehyde levels (Brooks <i>et al.</i>, 2009). Other treatments include antioxidants that may directly interact with acetaldehyde, but these mainly focused on reducing acetaldehyde accumulation in the blood, instead of directly treating the acetaldehyde accumulation in saliva (Essential AD2, n.d.; Vogt & Richie, 2007).</p></section><section id="sec3Content"><h2>OUR GOAL</h2><p class="detail-text"><b>Our goal is to reduce salivary acetaldehyde levels and the resulting increased cancer risks of ALDH2 deficiency</b> by delivering functional ALDH2. We envision ALDH2 to be delivered either in engineered probiotic strains or as a purified enzyme to maintain ALDH2 levels in the mouth.</p></section><section id="sec4Content"><h2>REFERENCES</h2><p style="padding-top: 0px !important; padding-left: 32px; font-size: 16px !important; max-width: 80%; white-space: pre-wrap; text-align: justify; line-height: 1.3; text-justify: inter-word;">Chang JS, Hsiao JR, Chen CH. (2017). ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective. J Biomed Sci. 24(1):19. | ||
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Revision as of 23:20, 16 October 2018
PROJECT BACKGROUND
WHAT IS ALDH2 DEFICIENCY?
ALDH2 deficiency, more commonly known as Alcohol Flushing Syndrome or Asian Glow, is a genetic condition which interferes with the metabolism of alcohol (Figure 1-1). Normally, ethanol is first converted to acetaldehyde (a toxic intermediate) by the enzyme alcohol dehydrogenase (ADH). Then, acetaldehyde is converted to acetate by the enzyme aldehyde dehydrogenase 2 (ALDH2), which is then safely metabolized in the body. People with ALDH2 deficiency, however, have a point mutation in the gene, which produces a less efficient ALDH2 (mutant: ALDH2*2) by lowering the binding affinity to its coenzyme NAD+ (Larson et al., 2005; Farrés et al., 1994). The enzymatic activity in individuals who are deficient can be as low as 4% compared to normal ALDH2 (wild type: ALDH2*1) activity (Chen et al., 2014; Zhou & Weiner, 2000; Farrés et al., 1994). As a result, acetaldehyde accumulates and induces an inflammatory reaction that causes the skin to flush or appear red after drinking alcohol (Ijiri, 1999). Facial flushing is the most obvious result of ALDH2 deficiency, but symptoms also include “headaches, nausea, dizziness, and cardiac palpitations after consumption of alcoholic beverages” (Chen et al., 2014).
Figure 1-1: Acetaldehyde accumulates in ALDH2 deficient individuals. Ethanol is first converted to a toxic intermediate, acetaldehyde, by alcohol dehydrogenase (ADH). For individuals with wild type ALDH2, acetaldehyde is converted to acetate by ALDH2*1. However, people who are ALDH2 deficient carry the mutant ALDH2*2, which cannot fully convert acetaldehyde into acetate, and acetaldehyde accumulates as a result. (Figure: Caroline C)
ALDH2 deficiency affects 540 million people--8% of the world population. In East Asia (which includes Japan, China, and Korea), this is a much bigger problem, where the number rises to 36% (Brooks et al., 2009). In our home, Taiwan, approximately 47% of the population carries this genetic mutation--the highest ALDH2 deficient percentage in the world (Chang et al., 2017).
HEALTH CONCERNS & RISKS
One of the biggest problems of ALDH2 deficiency is that while people recognize that flushing occurs, they are not aware that it is actually dangerous. According to our survey, which sampled close to 700 people around Taipei, many people misunderstood the causes and effects of alcohol flushing. For example, many people thought that turning red is the result of low alcohol tolerance, healthy liver functions, and fast metabolism--this is the opposite of the truth! These findings suggest a need for more public awareness about the health implications of ALDH2 deficiency. (To see our survey results, click here)
Turning red after consuming alcohol may seem like a mere social inconvenience. Yet, behind this red complexion lies a far more serious problem. The International Agency for Research on Cancer classifies acetaldehyde associated with alcohol consumption as a Group 1 carcinogen (IARC, n.d.). Alcohol and acetaldehyde have been shown to reduce thymidine incorporation into DNA, interfering with DNA synthesis (Dreosti et al., 1981; Seitz & Stickel, 2010). In other studies with human lymphocyte cells, acetaldehyde increased chromosome damage or the frequency of sister-chromatid exchanges (Obe et al., 1986; Helander & Lindahl-Kiessling, 1991; Maffei et al., 2002). When rats were exposed to acetaldehyde, inhalation led to abnormal changes in the nasal mucous membrane, such as degeneration of the tissue, increased cell proliferation, and the development of carcinomas (Woutersen et al., 1986).
Figure 1-2: There are 14 grams of ethanol in each serving of alcohol, which is around 148 mL of wine, 355 mL of beer, and 44 mL of spirit such as whiskey or tequila (NIAAA, n.d). (Figure: Caroline C)
Acetaldehyde levels over 50 μM are considered toxic and cause mutations in DNA (Yamaguchi et al., 2012; Kocaelli et al., 2014). In human studies where roughly 2 to 3 servings of alcohol (0.5-0.6 g alcohol/kg body weight) were ingested (Figure 1-2), salivary acetaldehyde levels in some individuals increased to over 100 μM (Homann et al., 1997a; Yokoyama et al., 2008), compared to normal levels of <20 μM without drinking (Lachenmeier & Monakhova, 2011). For people who carry normal, functional ALDH2*1, acetaldehyde can quickly get broken down (Figure 1-3).
Figure 1-3: Salivary acetaldehyde levels are much higher in heterozygous (ALDH2*1/*2) individuals, compared to homozygous wild type (ALDH2*1/*1) individuals. Acetaldehyde levels were recorded after drinking 0.6 g ethanol/kg body weight. Salivary acetaldehyde levels are also significantly higher than blood acetaldehyde after drinking (Figure from Yokoyama et al., 2008).
For those who are ALDH2 deficient and drink, however, acetaldehyde can accumulate to toxic levels. The strongest effects are seen in the mouth. Studies show that after alcohol consumption, salivary acetaldehyde levels are significantly higher than blood acetaldehyde levels (Stornetta et al., 2018; Yokoyama et al., 2008) (Figure 1-3). Since there are other aldehyde dehydrogenases (such as ALDH1A1; Ueshima et al., 1993) throughout the body that can help metabolize acetaldehyde, blood acetaldehyde concentrations remain relatively low. Most importantly, ALDH2 levels are much higher in the liver, which can break down most acetaldehyde before it enters the bloodstream (Oyama et al., 2005). Maybe because of this, ALDH2 deficiency does not seem to be directly associated with the development of liver, breast, colorectal, or other common alcohol-related cancers (Väkeväinen et al., 2000; Chang et al., 2017).
These results could also explain why the effects of ALDH2 deficiency are mainly localized rather than widespread throughout the body. Heightened salivary acetaldehyde levels increase the risks of developing esophageal and head and neck cancers. In vivo studies with rats have shown that acetaldehyde administered orally has a tumor-promoting effect (abnormally fast cell growth and division) on the upper respiratory-digestive tract (Homann et al., 1997b). Depending on how much alcohol is consumed, people with ALDH2 deficiency are two to eight times more likely to develop head and neck cancers (which includes oral cancer, pharyngeal cancer, laryngeal cancer, etc.), and two to twelve times more likely to develop esophageal cancer compared to people with normal ALDH2*1 (Chao et al., 2000; Yang et al., 2007; Yokoyama, 2001; Matsuo et al., 2001; Cui et al., 2009; Lee et al., 2007; Wu et al., 2013; Huang et al., 2017; Hiraki et al., 2007).
CURRENT SOLUTIONS
Today, the solutions for treating flushing include simply using cosmetics to conceal the flushing, or using antihistamines to prevent the release of histamines, which leads to the resulting redness (Chrostek et al., 2007; Miller et al., 1998; Quertemont et al., 2006; Eriksson, 2001). These solutions, however, do not actually address the buildup of acetaldehyde, the main contributor to increased esophageal and head and neck cancers (Sunset, n.d.; Essential AD2, n.d.). On the contrary, these options may actually increase health risks, as they cover up the visible symptoms without reducing acetaldehyde levels (Brooks et al., 2009). Other treatments include antioxidants that may directly interact with acetaldehyde, but these mainly focused on reducing acetaldehyde accumulation in the blood, instead of directly treating the acetaldehyde accumulation in saliva (Essential AD2, n.d.; Vogt & Richie, 2007).
OUR GOAL
Our goal is to reduce salivary acetaldehyde levels and the resulting increased cancer risks of ALDH2 deficiency by delivering functional ALDH2. We envision ALDH2 to be delivered either in engineered probiotic strains or as a purified enzyme to maintain ALDH2 levels in the mouth.
REFERENCES
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Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China. Int J Cancer. 132(8):1868-77. Yang SJ, Wang HY, Li XQ, Du HZ, Zheng CJ, Chen HG, Mu XY, Yang CX. (2007). Genetic Polymorphisms of ADH2 and ALDH2 Associated with Esophageal Cancer Risk in Southwest China. World J Gastroenterol. 13(43):5760-5764. Yamaguchi H, Hosoya M, Shimoyama T, Takahashi S, Zhang JF, Tsutsumi E, Suzuki Y, Suwa Y, Nakayama T. (2012). Catalytic removal of acetaldehyde in saliva by a Gluconobacter strain. J Biosci Bioeng. 114(3):268-74. Yokoyama A, Muramatsu T, Omori T, Yokoyama T, Matsushita S, Higuchi S, Maruyama K, Ishii H. (2001). Alcohol and Aldehyde Dehydrogenase Gene Polymorphisms and Oropharyngolaryngeal, Esophageal and Stomach Cancers in Japanese Alcoholics. Carcinogenesis. 22(3): 433-439. Yokoyama A, Tsutsumi E, Imazeki H, Suwa Y, Nakamura C, Mizukami T, Yokoyama T. (2008). Salivary acetaldehyde concentration according to alcoholic beverage consumed and aldehyde dehydrogenase-2 genotype. Alcohol Clin Exp Res. 32(9):1607-14. Zhou J, Weiner H. (2000). Basis for half-of-the-site reactivity and the dominance of the K487 oriental subunit over the E487 subunit in heterotetrameric human liver mitochondrial aldehyde dehydrogenase. Biochemistry. 39(39):12019-24