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Home >> Life
UPDATED: 11:33, July 15, 2005
A new look at the causes of cancer
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Many turn pale at the mere mention of cancer. After a war on the disease lasting several decades, the killer still lacks an effective cure.

But by delving into etiology, the branch of medicine that researches the causes and origins of a disease, researchers hope to find weapons to defeat it.

Since the 1960s, Chinese researchers at the Cancer Institute, Chinese Academy of Medical Sciences, have been tracing the environmental factors that cause esophageal cancer.

Esophageal cancer is the eighth most common cancer and the fifth most common cause of cancer deaths in the world. About 250,000 esophageal cancer cases are diagnosed each year in China, accounting for half of the world's total.

Once diagnosed, survival rates for esophageal cancer are poor: 75 per cent of patients die within one year, and the five-year survival rate is only 5 to 10 per cent.

Esophageal cancer occurs more often in specific regions. Most victims live in the "esophageal cancer belt," which stretches from the central part of North China westward through Central Asia to northern Iran.

In China, esophageal cancer occurs mainly in areas south of the Taihang Mountains on the borders of three provinces Henan, Shanxi and Hebei.

In Linxian County, Henan Province, the incidence of esophageal cancer among the local population is higher than other regions, about 150 per 100,000 residents. The mortality rate of the disease was around 100 in every 105 cases for both males and females in the 1990s.

"The high incidences of the cancer in small geographic confines suggest that specific environmental factors may play a predominant role in its etiology," said Professor Lin Dongxin, director of the Department of Etiology and Carcinogenesis of the Cancer Institute.

After decades of research in Linxian, scientists at the cancer institute have already proved that nitrosamines, a carcinogenic organic compound, from poorly preserved foods were a principal cause of esophageal cancer.

Linxian was a poor county in the past and a lot of people in the region suffered from malnutrition. They had a low consumption of vegetables and fruit, a major source of folate, of which deficiency in the body is associated with an increased risk of esophageal cancer.

Other etiological factors may include mouldy food and pickled vegetables containing mycotoxins and other carcinogens.

"However, environmental epidemiological research could not explain why only a small proportion of people in the county develop the cancer while the majority of local residents remain healthy even though they live in the same environment and share a similar diet," Lin said.

"There must be some genetic differences in the patients which make them more susceptible to the risk factors," said Lin.

Finding the links

It has taken epidemiologists like Professor Lin years to make the possible link between genes and environment, likening the relationship to that of a loaded gun and its trigger. A loaded gun by itself causes no harm, but once triggered, the gun could kill.

In fact, the concept of the environmental genome project emerged only about 10 years ago, with its goal to identify the causes of cancer with combined environmental and genetic approaches.

"Like hypertension, diabetes, and Alzheimer's disease, cancer falls into the category of complex diseases," Lin said.

"It is a product of the interaction of a whole variety of genetic and environmental factors over a long time," said Lin, one of the forerunners in China to explore cancer causes by observing the interaction between environment and genes.

After finishing his postgraduate studies in toxicology at Beijing Medical University in 1986, Lin worked at the International Agency for Research on Cancer, Lyon, France, for two years, and then for four years conducted research at the National Centre for Toxicological Research under the Food and Drug Administration (FDA) in the United States.

He became fascinated with the effect toxins had on the human body and started to focus on DNA adducts in carcinogens and their interaction with the environment.

In 1994, Lin returned to China and continued his research with the Cancer Institute.

"Before I came back, Chinese researchers still emphasized traditional environmental research, such as diet and lifestyle. So many of my colleagues did not understand or even doubted what I was doing," said Lin.

However, he was to convince them that genetic analysis could be more effective in catching the killer disease off guard.

For esophageal cancer, Lin and his colleagues examined a panel of susceptibility biomarkers to define individuals at high risk.

DNA sequence variations between the patients and healthy controls in folate biotransformation genes, carcinogen-metabolizing genes, and DNA repair genes, made a significant difference in an individual's susceptibility to cancer.

When observing the interaction between environment and genetic variation, Lin emphasized that the researchers must clearly identify the environmental factors.

Over the past few years, he has also targeted lung cancer.

Smoking is an established cause of lung cancer, enhancing people's susceptibility to the disease three fold. The risk is greatest among those who begin to smoke when young and continue throughout their lives.

During the last decade, the incidence and mortality rates of lung cancer in China have increased significantly. Since China accounts for one third of the world's one billion tobacco smokers, a major lung cancer epidemic is predicted.

"However, although the risk of lung cancer has been conclusively associated with tobacco smoking, fewer than 20 per cent of smokers develop the disease," said Lin. "It indicates that people with varied genetic components might respond differently when exposed to smoking."

Their research has suggested that variations in genes control the cancerous cells and their changes, which makes some people more susceptible to lung cancer than others.

Also, defects in genes' ability to self-repair heighten the risk of cancer.

A wide range of DNA damage could be induced by the normal metabolic process, or by environmental factors. If not repaired, such damage can lead to gene mutations and genomic instability, which in turn cause cells to transform from benign to malignant.


Lin and his colleagues believe that once they identify the genetic susceptibility factors for cancer at the molecular level, they will be able to identify at-risk individuals with useful biomarkers, and target others for cancer prevention.

But simply persuading the public to give up smoking has proved difficult.

"Smokers can cite a myriad of examples from their neighbours who are heavy smokers in their 80s, but still remain pretty healthy. So it would be hard to convince them that smoking harms their health," said Lin.

What Lin and his colleagues are doing at present is proving that people with varied genes are more susceptible to lung cancer.

"So a simple blood test could identify the high-risk group. Then education specifically aimed at the group would be much more effective," said Lin.

In addition, gene testing could identify workers who are more susceptible to certain cancers when exposed to industrial hazards.

The incidence of a type of cancer is commonly related to a particular environment. So better prevention should depend on the identification of cancer-inducing environmental risks, according to Gao Yutan, director of department of epidemiologists of the Shanghai Cancer Institute.

The environmental factors to be examined include not just water and air but also lifestyles, such as smoking, alcohol and inactivity.

According to Gao, the cancer pattern in Shanghai has changed a great deal in recent years. The high-incidence cancers of the past, such as stomach cancer, esophageal cancer, and liver cancer, are on the decline, while colon cancer, breast cancer and biliary duct cancer are spiking.

"These cancers are unexceptionally related to a more high fat Westernized diet and reduced intensity of exercise," said Gao.

Nowadays, the traditional Chinese dietary pattern of high vegetable and plant protein consumption, which helps prevent these cancers, has been neglected.

"It is our priority to make clear through epidemiological study how nutrient intake and physical exercise are contributing to lowering the risk of cancer," said Gao. "A quantitative result will surely help the public to choose a healthier lifestyle."

Source: China Daily

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