Hepatocellular carcinoma is a common cancer worldwide. The incidence in the East is very much higher due to endemic chronic hepatitis B virus (HBV) infection in the population. The incidence of HCC has been increasing steadily in USA and the major risk factor for HCC in US is chronic hepatitis C virus (HCV) infection. In 1975, the total incidence of HCC was approximately 1.59 per 100,000 person-years. By 2006, this had reached 4.82 per 100,000 person-years and this increase has been attributed to the increasing numbers of Asian immigrants in the United States. However, a presentation at the recent 101^st Annual Meeting of the American Association for Cancer Research (AACR) has come up with a surprising culprit (Abstract 1816, presented Arpil 19, 2010).

Researchers from the National Cancer Institute (NCI) reviewed data from the NCI SEER database. The case population studied consisted of 5607 people diagnosed with HCC. They examined the odds ratio of an individual developing HCC with the risk factors of HCV infection, HBV infection, alcohol-related disease, rare metabolic disease, diabetes and obesity. (Odds ratio tells you how much more likely it is that you are going to develop the condition compared with someone without the risk factor.) HCV infection has the highest odds ratio of 44.26 (ie 44 x more likely than a non HCV infected person). The odds ratios for HBV infection, alcohol-related disease, rare metabolic disorder, diabetes and obesity were 13.37, 4.43, 3.51, 2.37 and 1.53, respectively. However, the researchers found that diabetes was associated with the greatest percentage of cases (33.5%). The other associations were alcohol-related disorders (23.9%), HCV infection (20.7%), HBV infection (5.7%), rare metabolic disorders (3.1%) and obesity (2.7%).

The incidence of obesity and diabetes mellitus is increasing worldwide and the Asian population has not been spared. While chronic HBV infection is the most important risk factor for HCC in Asia, the general population and clinicians need to be aware that diabetes and obesity are also associated with HCC. The above study found that 67.9% of Asians with HCC had one or more of the identified risk factors. Both obesity and diabetes can be helped by adopting a prudent life style - maintaining a healthy body starts with you!

Does your face go red after a glass of wine or beer? If the answer is yes, then you have the so-called alcohol flushing response, also known as ‘Asian glow’ or ‘Asian flush’. This characteristic physiological response to drinking alcohol includes facial flushing, nausea and tachycardia and is seen in approximately 36% of East Asians (Japanese, Koreans and Chinese).  The response is due to an inherited deficiency in the enzyme aldehyde dehydrogenase 2 (ALDH2). Although most if not all of the East Asian public is aware of this alcohol flushing response, few realise that ALDH2-deficient individuals are at much higher risk of developing oesophageal cancer from alcohol consumption when compared to individuals with fully active ALDH2. It is estimated that there are at least 540 million ALDH2-deficient individuals worldwide and this represents about 8% of the world population.

Ethanol is first metabolised by alcohol dehydrogenase (ADH) into acetaldehyde, which is a mutagen and animal carcinogen. It causes DNA damage and has other cancer promoting effects. Acetaldehyde is then metabolized to acetate mainly by ALDH2. There are 2 main variants of ALDH2 in the East Asian population – the normal one (ALDH2 Glu/Glu ) with full activity and the abnormal one (ALDH2 Lys/Lys) with no activity at all. If you are a heterozygote, then you have a mixture of the two (ALDH2 Glu/Lys) and you have some ALDH2 activity.

In individuals with no ALDH2 activity, the accumulated acetaldehyde will cause intense facial flushing, nausea, tachycardia and histamine release which is so unpleasant that the individual is unable to consume any significant amount of alcohol. Thus, the individual is protected from the increased risk of oesophageal cancer from alcohol consumption. Heterozygotes have a low level of ALDH2 activity and so develop tolerance to acetaldehyde and the flushing response, thus, becoming regular heavy drinkers with the associated increased risk of developing oesophageal cancer. Studies in Taiwan and Japan have shown that alcohol consumption in ALDH2 heterozygotes increased their risk of oesophageal cancer by 3.7 to 18.1 times.

A simple but accurate way to determine if you are ALDH2 deficient is to answer yes or no to the following 2 questions: (1) Do you have a tendency to develop facial flushing immediately after drinking a glass (about 180 cc) of beer? (2) Did you have a tendency to develop facial flushing immediately after drinking a glass of beer in the first one or two years after you started drinking? If you answer yes to either question then you are considered ALDH2 deficient. ALDH2-deficient individuals should be warned about their increased risk of developing oesophageal cancer with alcohol consumption.

What would be the impact on oesophageal cancer risk if you, an ALDH2 heterozygote, went from a heavy (≥ 18 units / week) or moderate (9 – 17.9 units / week) drinker to a light (1 – 8.9 units / week) drinker? It has been calculated that 53% of oesophageal squamous cell carcinoma might be prevented in the Japanese male population if moderate or heavy drinking heterozygotes became light drinkers!

(If you wish to read about Asian glow in more detail, please go to www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000050)

The World Cancer Research Fund (WCRF) and its sister organization, the American Institute for Cancer Research (AICR) in their recent report titled ‘Policy and Action for Cancer Prevention’ stated that approximately one third of common adult cancers in the US may be preventable. (This is not including those which can be prevented by not smoking.) The WCRF and AICR estimated that eating a nutritious diet, being physically active and keeping body fat under control may prevent:

• 38% of breast cancers
• 45% of colorectal cancers
• 36% of lung cancers
• 39% of pancreatic cancers
• 47% of stomach cancers
• 69% of esophageal cancers
• 63% of cancers of the mouth, pharynx, or larynx
• 70% of endometrial cancers
• 24% of kidney cancers
• 21% of gallbladder cancers
• 15% of liver cancers
• 11% of prostate cancers

According to the report, diet, physical activity and limited body fat could prevent 34% of these 12 cancers overall and 24% of all cancers.

A study from the Karolinska Institute followed 45,920 Swedish male conscripts from the period 1969 - 70 for 38 years and examined the effects of overweight in adolescence on subsequent adult mortality (BMJ 2009; 338: b496). Compared with normal weight [body mass index (BMI) 18.5 – 24.9 kg/sq.m] men, the mortality risk in overweight (BMI 25 – 29.9) and obese (BMI ≥ 30) men was increased by 33% and 114%, respectively. The risk was not increased in underweight men, but in those who were extremely underweight, BMI < 17, the risk of mortality was increased by 33%. The risk of mortality in light (1 – 10 cigarettes / day) and heavy (> 10 / day) smokers was also increased by 54% and 111%, respectively, when compared to non-smokers. (Since the start of this study the number of overweight adolescent men in Sweden has tripled and the number of those who are obese has increased 5 fold. Fortunately, the number of smokers has halved.)

Another study looked at the effects of alcohol consumption on the incidence of cancer risk in 1,280,296 women involved in The Million Women Study (J Natl Cancer Inst 2009; 101: 296 – 305). They attended breast cancer screening clinics in the United Kingdom from 1996 to 2001. The average follow-up time was 7.2 years. The 5 categories of alcohol intake were 0 (24%), up to 2 (29%), 3 – 6 (23%), 7 to 14 (19%) and at least 15 (5%) drinks of 10 g of alcohol (= 1 unit) / week. Increasing alcohol intake was associated with an increased risk of specific cancers. The excess cancer incidence of these cancers, up to 75 years of age, with 10 g increase in daily alcohol intake were:

• Oral cavity and pharynx – 1 per 1000
• Oesophagus – 0.7 per 1000
• Larynx – 0.7 per 1000
• Rectum – 1 per 1000
• Liver – 0.7 per 1000
• Breast – 11 per 1000

To put it another way, the researchers estimated that the background incidence of cancers among women in developed countries was 118 cancers diagnosed per 1000 women up to the age of 75 years. Drinking 1 unit per day increased this by an extra 15 cancers per 1000 women and 2 drinks a day  increased this an extra 30 cancers per 1000 women; the majority of the cancers would be breast cancer.

Most cancers are not inherited. For the small proportion of inherited cancers, your cancer risk is not within your control. For most of us, how you lead your life can impact on your cancer risk. Leading a healthy lifestyle does not reduce your cancer risk to zero; it does however reduce your odds of developing cancer. Do not think that regular health checks will save you from cancers. You hope that the checks will help you detect the cancer at an earlier stage, and that is no guarantee either. A healthy lifestyle has no downside. Embracing it might just save your life!