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Is There a Relationship between Aflatoxin and Liver Cancer?

Posted on August 7, 2019 by Josephine
Is There a Relationship between Aflatoxin and Liver Cancer!?

What is the exposure of aflatoxin?

Now we have a preliminary impression of aflatoxin in food. That is, aflatoxin is almost ubiquitous, and regardless of staple food, a seasoning, or a hobby food, it is difficult to avoid the presence of aflatoxin. The problem now is that existence does not necessarily pose a threat to you. For example, two people eat rice. One person can eat 1000 grams of rice a day, and another person who eats like a kitten, eats only 50 grams of rice a day, so the impact of aflatoxin on two people may be different by different content of aflatoxin in rice.

A new concept can be defined that the amount of aflatoxin ingested (including respiratory inhalation and skin absorption) into the stomach is called exposure of aflatoxin (ng). Relative exposure refers to the daily exposure in per unit weight (nacks per kilogram per day). Sometimes the exposure is the same as the relative exposure, which can be judged from the weight.

Aflatoxin is not a carcinogenic substance, and only a small amount of AFBO converted into aflatoxin is a possible carcinogen. Furthermore, we can define another new concept that effective exposure is called active exposure, the amount of AFBO, which can be correlated by measuring AFBO-N7-guanine in the urine. However, studies of active exposures are difficult to find.

We now give an example in the calculation of exposure. This person weighs 60 kilograms, eats 250 grams of rice a day, and be calculated about the exposure of a certain aflatoxin B1.

Referring to the data of Shanghai Lulu University Ph.D. Ye Lu and other data, the average content of aflatoxin B1 in Shanghai rice is 1.926μg/kg. Then, the exposure amount of aflatoxin B1 is 1.926×0.250=0.48μg/d.

The same exposure is 0.48μg/d. If the bodyweight is different, and the effect is different. Therefore, we should also calculate the exposure of certain unit weight. 0.48/60=0.0080μg/(kgBM·d).

The number is too small, and we change the unit and use nanograms as mass measurement. 1 ng = 1000 micrograms. The exposure of a certain unit weight is 8.0ng / (kgBM · d).

The amount of exposure can not depend on the ingestion of rice, and we will now calculate his total exposure. Except for eating rice, he eats vegetables and fruits that do not contain aflatoxin. He uses peanut oil for cooking, and the content of aflatoxin B1 is 1μg/kg with the 20 grams dosage. The soy sauce is used 5 Gram, and the content of aflatoxin B1 is 1 μg / kg. Chili powder is used 1 g, and the content of aflatoxin B1 is 12 μg / kg. After the meal, he drank a pot of Pu'er tea. He knows that the content of aflatoxin B1 in Pu'er tea is 2.73μg/kg, and he used 3 grams of tea. He uses boiling water to wash tea before brewing tea, and it can wash off 50% of the aflatoxin in tea. The solubility of water is 36.3 g/100 ml in aflatoxin at 97 ° C, which is easily dissolved in hot water.

Peanut oil exposure: 1 × 0.020 / 60 = 0.00033 μg / (kg BM · d) = 0.33 ng / (kg BM · d)

Soy sauce exposure: 1 × 0.005 / 60 = 0.000042 μg / (kg BM · d) = 0.042 ng / (kg BM · d)

Paprika exposure: 12 × 0.001 / 60 = 0.00020 μg / (kg BM · d) = 0.20 ng / (kg BM · d)

Pu'er tea exposure: 2.73 × 0.003 × 50% / 60 = 0.000068 μg / (kg BM · d) = 0.068 ng / (kg BM · d) total exposure: 8.0 + 0.33 + 0.042 + 0.20 + 0.068 = 8.64 ≈ 8.6 ng / (kgBM·d)

I use rounding rules to calculate and remain only two significant digits in the total exposure. Rounding rule is the knowledge of elementary mathematics. Why use rounding rules to keep only two significant digits? The original calculation has zeros and even can have four digits. However, when we calculate the sub-exposure, we temporarily retain two significant digits. After the sum, you can only keep two significant digits, because the decimal point, the third digit, and the fourth digit is meaningless. We reinforce the concept of effective numbers. And a valid number is to tell others that the number here is accurate, retaining a few significant digits.

I am not tired of revisiting primary school mathematics here, but to strengthen our concept of effective numbers. To calculate the exposure of rice, I only take two valid figures. Why are two and not three? I am telling you an amazing secret. The average content of aflatoxin B1 in rice given by Shanghai Jiaotong University Ye Lu et al. is 1.926μg/kg. The content is not standardized, because the allowable error of the content of the aflatoxin detection method is 20% Or 60%! The standard is not accurately, and you can keep two significant digits, and 1.926 should be rounded to 1.9. Just like the example of calculating exposure, his exposure to aflatoxin in rice is 8.0 ng/(kgBM·d), and his exposure to tea is 0.068 ng/(kgBM·d). The number only effective in one decimal place, and the third and fourth numbers after the decimal point directly discard that useless in the formula calculation of exposure.

The important conclusion is that the exposure of a person in aflatoxin depends on his weight and the fraction is negligible. In the future, when you encounter that people who have eaten 8 ng/(kgBM·d) of rice are depressed due to exposure of aflatoxin in peppers with 0.08 ng/(kgBM·d). Just let him understand the principle for rounding off and the number of significant figures.

Now, look at the exposure of aflatoxin of residents in the country and some areas. Wang Jun, from the Center for Nutrition and Food, Chinese Center for Disease Control and Prevention, said in the Evaluation of Aflatoxin Dietary Exposure in Chinese Population (Chinese Journal of Preventive Medicine, Vol. 43, No. 6) and Chinese Prophylactic Medicine Magazine that the exposure of aflatoxin in population is calculated by the level of aflatoxin contamination in the food and the intake of aflatoxin-containing food. Chongqing, Fujian, Guangdong, Guangxi, Hubei, Jiangsu, Shanghai, Zhejiang, Jilin, Shaanxi, Shandong, Henan, Hebei and other provinces (cities) collect and test local representative and real-time food samples according to the requirements of the National Food Contaminant Testing Program. The content of aflatoxin in food is determined according to the High-Performance Liquid Chromatography Method for Determination of Aflatoxins B1, B2, G1, G2 in Food.

The data on food intake of Chinese people comes from the 2002 Survey of Nutrition and Health Status of Chinese Residents. The results showed that the average content of aflatoxin in corn, peanut, peanut oil and rice was 22.50, 2.61, 8.00, 1.47 μg/kg respectively. The average standard person (referring to adult men engaged in light physical labor) had a total intake of 257.53 g. / (d · person), and the total exposure is 665.43 ng / (d · person). The exposure of different people, different regions, different age groups, and different genders varies greatly. The exposure of high-consumption standard people can reach 24787.20 ng/(d·person), and the high-standard consumption standard in rural areas can reach 29370.42 ng/(d·person). The high consumption here is not a luxury consumer who spends a lot of money, but a person who eats food with a lot of aflatoxins. Their exposure is dozens of times more than the average standard person.

Li Shan, from the Institute of Public Health, Henan Provincial Center for Disease Control and Prevention, said in the Evaluation of Dietary Exposure of Aflatoxin B1 in Henan Province and Modern Preventive Medicine, Vol. 43, No. 6 in 2013-2014 that aflatoxin was monitored in some foods and used the point-evaluation method to evaluate the exposure level of aflatoxin B1 in residents' diets, combining with the food intake data of the Henan Provincial Residents' Nutrition and Health Survey in 2002. The results showed that the dietary exposure of aflatoxin B1 was 2.32 ng/(kgbw·d) in the general population, 2.76 ng/(kgbw·d) in rural areas, and 1.40 ng/(kgbw·d) in urban residents. It seems that the exposure of aflatoxin B1 in the Henan population is not high. It may be related to the staple food with pasta in Henan population. The content of aflatoxin B1 in wheat is lower than that in rice. The average value of aflatoxin B1 in wheat in Henan Province is 0.5 μg/kg. Wheat exposure accounted for 82.42% of total exposure.

Li Ke, Shenzhen Futian District Center for Disease Control and Prevention, said in the Evaluation of dietary exposure of aflatoxin in food, oil and food in Shenzhen and Health Research (2014, issue 4) that through the levels of toxin contamination and dietary consumption of the population in Cereals, food, and oil products in Shenzhen estimated exposure of aflatoxin B1 and total exposure aflatoxin. The results showed that the daily dietary exposure of aflatoxin B1 in the 2-6-year-old group, 7-14-year-old group, 15-50-year-old group and 50-year-old group in Shenzhen area in male was 0.320, 0.385, 0.401, and 0.398 ng/kg BW respectively. And female was 0.282, 0.222, 0.367, and 0.470 ng/kg BW respectively. We have already seen the test report of Li Ke et al. The exposure of aflatoxin B1 and total aflatoxin in Shenzhen grain and oil foods are in line with EU standards, and the average exposure of Shenzhen residents calculated is also very low. In our previous examples in calculating exposure, his daily exposure is 8.6ng / kg BW, which is much higher than the Shenzhen residents.

We already know that aflatoxin is not a carcinogen, but a carcinogen precursor. Aflatoxin B1 produces an active carcinogen AFBO under the catalysis of a P450 enzyme. However, a large number of AFBI and AFBO are metabolized into non-toxic substances, which are excreted from the body and there is little AFBO left in the body. Therefore, to study the relationship between aflatoxin and primary liver cancer (HCC), exposure of aflatoxin has no etiology and statistical significance. But it can use Aflatoxin biomarkers such as AFB1-albumin in serum, AFM1 in urine, AFBO-N7-guanine or carboxamide-based derivatives, AFBO-thiol urea in the study of the relationship between aflatoxin and primary liver cancer (HCC).

Is There a Relationship between Aflatoxin and Liver Cancer!?

Aflatoxin-HCC correlation

We talked about exposures of aflatoxin to study whether the exposure of aflatoxin is related to cancer (here mainly HCC or PCC).

The association is to investigate whether there is a statistically significant correlation between exposure and HCC. This is a kind of mathematical relationship, but whether it is an intrinsic functional relationship or causality needs to be in further research and conformation.

What is the association? For example, some people (a) like to eat tomatoes, and they eat one every day the previous year, eat two every day last year, eat three every day this year, and their deposit number was 10,000 yuan the previous year, was 20,000 yuan last year, and is 30,000 yuan this year. At this time, you are very clever to find that the more tomatoes the person eats, the more money he has. The number of his deposits is proportional to the number of tomatoes he eats. This is the correlation. In this example, the correlation coefficient R=1 (100% correlated), significance P = 0 (100% significant).

Now the object we observe is not a certain group, but a large group of people. They all eat tomatoes every day. Some people eat more and some eat less, and their deposits are different. What is the relationship between the number of tomatoes eaten every day and deposits? It's not so correctly, you have to use statistical methods to analyze.

Statistics is an indispensable mathematical tool for studying the relationship between aflatoxin and liver cancer. Maybe you said that the correlation between the number of tomatoes you eat and the number of deposits you mentioned is deceptive. I don't believe that eating tomatoes are related to deposits.

Although statistics is a mathematical approach that is not all unreliable, I want to tell you that this method is sometimes reliable. This is a scientific method and doesn't doubt about the science. There are many research reports on the correlation between aflatoxin and HCC.

China is a large country with a high incidence of liver cancer. Jiangsu, Shanghai, Zhejiang, Fujian, Guangdong, Hainan and Guangxi in the southeastern coastal areas are of high-incidence of liver cancer. In these areas, Jiangsu Qidong and Guangxi Fusui are two high-incidence areas. Let’s start with Jiangsu Qidong.

American scholar, Patricia et al. said in the article China Qidong Liver Cancer Prevention on Aflatoxin Biomarker Research Experience that primary liver cancer has been the leading cause of cancer death in Qidong, China. About 800 people died of primary liver cancer. It is worth noting that the exposure of aflatoxin in Qidong has dropped 40 times in the past 25 years, which may be caused by changes in the staple food from corn to rice. (See Chemical Progress, No. 9 of 2013) Unfortunately, the incidence of primary liver cancer in Qidong is still high, and the incidence of hepatitis B virus carriers or hepatitis B surface antigen-positive cohort is as high as 1800 to 2000 with every 100,000 people per year! Compared with the national average of 26.68 people per 100,000 people per year, it is a world of difference (see Chinese Journal of Epidemiology, 2012, issue 6). And It can not compare to cities or countries with 10 of 100,000 per year.

Despite the significant decrease in exposure of aflatoxin in Qidong, but the incidence of primary liver cancer did not decrease significantly. Wu Yan, from the Qidong Institute of Liver Cancer Prevention, Jiangsu Province, studied the association between exposure of aflatoxin and primary liver cancer (Chinese Journal of Practical Internal Medicine, Vol. 30, 2010). The authors selected AFM1 as a biomarker for exposure of aflatoxin. We already know that AFM1 is a metabolite of AFB1, so AFM1 in the test cohort can be used to represent the true exposure of aflatoxin. The author's team is targeted at people with high risk for primary liver cancer (HCC). In the high-risk area of HCC, 148 patients of 25-60 years old with high-risk of HBsAg(+)(hepatitis B surface antigen-positive) underwent a 20-year cohort prospective investigation, including 79 patients in AFM1-positive group and 69 patients in AFM1-negative group.

The method uses a high-affinity anti-AMF1 monoclonal antibody system, uses immunoconcentration technology, and a high-performance liquid chromatography series to measure the cumulative emission of AFM1 in urine samples, and the AFM1 accumulation is ≥5mg/mL (≤5mg/mL is negative (-)). The results showed that the incidence of HCC in the male group of HBsAg(+) and AFM1(+) accounted for 70.73% of the total incidence. The average incidence of HCC in 20 years was as high as 1845 per 100,000 people per year, significantly higher than AFM1 (- ) 869.7 people per 100,000 people per year. χ 2 = 6.86, P <0.01. Here you need to insert statistical knowledge. χ 2 = 6.86 (χ is the Greek letter) P < 0.01 is a statistical indicator. Epidemiological and etiological studies commonly use statistical methods to process data.

The authors' objects were hepatitis B surface antigen-positive and aflatoxin high-exposure populations. There are positive and negative HBsAg in the high-exposure population with hepatitis B. Obviously, the exposure of aflatoxin of the negative population here is still not a decimal, we see the negative incidence of HCC in the group is still as high as 869.7 people per 100,000 people per year, which is a sad thing. The high incidence of HCC in the Qidong area indicates that the exposure of aflatoxin in the population here is too high.

We can conclude that high exposure of aflatoxin is likely to be a cause of HCC. But you should not be too depressed. The authors studied the group with hepatitis B surface antigen-positive and aflatoxin double-exposure populations with a high rate. If it is negative for hepatitis B surface antigen and low exposure to aflatoxin, you will find that when the exposure of aflatoxin is low enough, you can't find a correlation between HCC and exposure of aflatoxin.

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