Lung Cancer--The Leading Killer of Taiwanese Women

Ever since it first topped the list of the ten major causes of death in 1982, cancer has remained the leading cause of death among the citizens of Taiwan. As lifestyles and dietary choices have changed, the relative rates of various kinds of cancer have shifted, and medicine has advanced in its treatment of some. Campaigns to universalize pap smears, for example, have meant earlier detection of cervical cancer and good prognoses for treatment; its mortality rate has dropped from 9.5 per 100,000 a decade ago to last year's 8.4 per 100,000. Some cancers, however, remain resistant to medical advances-among them, cancer of the lung.

Lung cancer rates are on the rise; treatment breakthroughs hard to achieve.

The nature of the risk

While it is the form of cancer with only the fifth highest incidence in Taiwan, lung cancer nevertheless causes the most fatalities. Since 1997, the mortality rate for lung cancer has several times surpassed that of liver cancer to rank highest-particularly among women, for whom it has been the biggest killer for many years. According to statistics from the National Health Research Institutes (NHRI), the incidence of lung cancer in Taiwan only continues to grow: in 1955, 2.67 males and 1.25 females out of 100,000 persons contracted the disease; in 1991, the respective figures were 25.42 and 10.85 per 100,000. With this ninefold increase over more than 30 years, Taiwan now matches the US and European countries as one of the regions with the fastest-growing incidences of lung cancer.

In recent years, about 7000 people per year in Taiwan have died of lung cancer, which accounts for 19.6% of total cancer deaths. As Lai Gi-ming, administration department director at the NHRI and chief executive officer of the Formosa Cancer Foundation says, "Lung cancer is Taiwan's greatest enemy."

Given the variety of cell types that make up the lung and which may undergo pathological changes, numerous forms of cancer may result. When it appears in the epithelial cells of the bronchi, it is known as squamous cell lung cancer; in the alveoli, it generally appears as an adenocarcinoma.

Clinically, lung cancers may be further divided into two main types-small-cell and non-small-cell lung cancers-based on their differing biological features and clinical manifestations. Statistics place the relative proportions of those two types in Taiwan at 12-15% for small-cell lung cancers and 85-88% for non-small-cell lung cancers.

The need for classification arises due to differences in treatment. Because small-cell lung cancers grow quickly, they are prone to spreading to other parts of the body (metastasis). They do respond to chemotherapy and radiation treatment, with chemotherapy the favored approach, but in most cases will recur within two years, and become drug-resistant too.

While non-small-cell lung cancers grow and spread relatively slowly, only about one-fourth are detected at an early, operable stage. That is, they are usually not discovered until they are inoperable. These patients tend not to respond well to either chemotherapy or radiation therapy, and recurrence or metastasis are common.

Among the Taiwanese, non-small-cell lung cancers predominate, including squamous-cell carcinomas, adenocarcinomas, and large-cell carcinomas. Recent years have seen adenocarcinoma of the lung predominating, especially among female patients, for whome it accounts for 70% of lung cancers and now ranks as a major cause of death.

Lai Gi-ming points out that these cancers most often occur at the extreme ends of the bronchi, so that any carcinogens reaching that area must have very small molecular structures.

Epidemiological research on lung cancer among Taiwanese women, led by DOH minister Chen Chien-jen, is yielding results.

Is it genetic?

Questions about the rising incidence of lung cancer deserve a serious response.

Smoking has always been considered the chief cause of lung cancer. Statistics show that male smokers are 22 times more likely to develop lung cancer than non-smokers, while female smokers are only 12 times more likely to do so. While this points up the strong link between smoking and lung cancer, it also shows that the link is less significant for women.

In addition, only 5% of Taiwanese women are smokers. Thirty percent of people over the age of 18 in Taiwan are smokers, but nearly 95% of those are men.

Many signs hint that factors besides smoking must be causing lung cancers among women, factors which physicians and epidemiologists are currently striving to discover.

Over the past four years, some initial results have come to light in a long-term research project on the epidemiology of adenocarcinomas of the lung among Taiwanese women, undertaken under the direction of health minister Chen Chien-jen with the support of the National Science Council.

In its search for the principal causes of this disease among women, the research places particular emphasis on molecular epidemiology. Chen Chien-jen points out that in most countries, lung cancer rates are six to ten times higher among men than women, whereas in Taiwan the ratio is only two to one. Furthermore, in those countries, lung cancer in women is typically linked with smoking (at a 50% rate or higher), though only about 10% of women with the disease in Taiwan are smokers.

These graceful wisps of incense smoke contain suspected carcinogens.

Lifestyles and lung cancer

According to Chen Chien-jen, case-controlled studies show that second-hand smoke and cooking-oil fumes are two environmental factors linked with lung cancer.

It is commonly understood that smoking adds significant risk, raising the risk of lung cancer by about three to five times. But far less acknowledged is the risk from the spouse who smokes-breathing second-hand smoke may also double the risk of lung cancer. Clearly, cutting out smoking is essential for preventing lung cancer.

In addition to these factors, cooking in a poorly ventilated kitchen also brings a twofold increase in lung cancer risk.

Lai Gi-ming points out that like the second-hand smoke thoughtfully "filtered" for others by the nicotine addict, cooking-oil smoke and soot are also relatively small-molecule carcinogens that easily travel to the extremities of the bronchi and lead to cancer.

Liu Jung-sen, attending surgeon in thoracic surgery at Cathay General Hospital, points out that the lung cancer rate among women in Xiong County in China's Hebei Province, who cook with coal in their cave dwellings, is eight times as high as in other regions.

Housewives also need to be aware of polycyclic amines in the kitchen, because statistics show that cooking without an exhaust hood to clear away oil smoke leads to a 2.47 times higher incidence of adenocarcinomas. And if animal fat is used in cooking, the rate increases another 3.32 times. In addition to lowering the height of the exhaust fans to better clear the smoke, foods should also be prepared by steaming, boiling, and braising in place of pan-frying, deep-fat frying, or fast-frying in the wok. Also to be avoided is waiting until the cooking oil begins to smoke before adding cooking ingredients. After cooking, letting the exhaust fan run another ten minutes helps prevent smoke residues from lingering in the air.

An excellent practice is simply avoiding smoke and soot. All kinds of dust, oil smoke, coal smoke, and even incense smoke contain carcinogens.

Another focus of research, in addition to environmental factors, is genetic factors.

Yang Pan-chih, internist in thoracic medicine at National Taiwan University Hospital (NTUH), points out the abnormally high incidence of adenocarcinomas of the lung in Taiwan, Hong Kong, Singapore, and mainland China's southeastern coastal regions. That type of cancer accounts for 70% of all lung cancer in Taiwan, as compared with only 35% in the US and Europe, leading to speculation about genetic influences. Chen Chien-jen notes that the risk of this cancer is approximately two to five times higher for the mothers or daughters of females with the disease, and tragically, sometimes succeeding generations of women in the same family all develop this cancer. Aside from the environment, shared genetic factors may be the chief reason for such occurrences.

At present, through the combined efforts of NTUH and Veterans General Hospital, the NHRI have been able to identify over 20 genes related to lung cancer. They include CAP1A1, CAP1A2, and CAP2C19, genes having to do with drug metabolism, DNA repair enzymes, and female hormone receptors, though finding the mechanisms directly responsible for causing cancer will require further research. Chen Chien-jen notes that if this research succeeds, genotyping may be used to identify those most susceptible, who can then be given regular follow-up exams.

Smoking is the chief cause of lung cancer. In 2000, tens of thousands of sick smokers filed a class-action suit in Florida seeking damages for the "millions of American lives taken" by tobacco companies. Courts award US$145 billion in punitive damages.

A two-front battle

In its fight against the great killer lung cancer, medical research in Taiwan is searching for risk factors through epidemiology, and looking for new breakthrough treatments.

While medicine has made gains in treating many cancers, the special problems of lung cancer have often left it resistant to those breakthroughs.

First, there is the great difficulty of early discovery.

"The stage of cancer affects the prognosis." So observes Liu Jung-sen, attending surgeon in thoracic surgery at Cathay General Hospital, noting that adenocarcinomas grow at the outer reaches the lung. This cancer has no initial symptoms, and by the time it invades the nerves, blood vessels, or bronchial tubes, and symptoms appear such as coughing, chest pain, breathing difficulties, or coughing up blood, the disease has often reached the third stage. Sufferers often mistake coughing and shortness of breath for the common cold, and only a further examination reveals the late-stage cancer. For some, the cancer has already spread, and it is only symptoms such as headaches or abnormal bone fractures that provide clues of the cancer.

Former NTU business administration professor Weng Jing-min, memorialized by students who recorded his struggle with the disease as "the professor among the stars," lived no more than half a year after being diagnosed with an adenocarcinoma of the lung. Former legislator Lu Hsiu-i , National Security Bureau director Yin Tsung-wen, and vice-president of the Judicial Yuan, Lu Yu-wen have also been victims of the same cancer.

What about X-rays?

Lai Gi-ming notes that a tumor must be at least one centimeter in size to be detected by a chest X-ray, and the tumor may unfortunately be hidden from view by the heart or ribs. But even given a successful X-ray, the cancer may have already begun spreading when the tumor was only 0.2 centimeters in size.

On top of all this, the lungs provide us with oxygen exchange: as the body's entire stock of blood passes through the lungs, the chances of a cancer cell being carried away are greater; the lungs also absorb more of the body's waste products than any other organ, so that cancer cells may also easily pass through the lymph system to the lymph nodes.

In addition, the lungs also perform detoxifying functions which may seriously hamper the effectiveness of the toxic drugs typically used in chemotherapy, and lead to its failure.

Death Rates from Principal Types of Cancer among Women in Taiwan, 1983-2003 source: Department of Health

Seeking combination therapies

All of these unique factors add up to three major obstacles: lung cancers are difficult to detect, spread easily, and are tough to treat. Unfortunately, cancer patients in Taiwan face relatively low survival rates: for third-stage lung cancer, the survival rate over the last five years has been below 20%, less than half the 40% rate seen over the last three years in the US.

According to Lai Gi-ming, the reason for may be Taiwan's relatively non-aggressive approach to treatment. Currently, in most countries, surgical removal is the norm for non-small-cell lung cancers, followed by radiation therapy and chemotherapy. In those countries, even some inoperable cancers discovered very late are tackled aggressively through a combination of chemotherapy and radiation therapy, to reduce the size of the tumor until surgical removal becomes possible. This raises the survival rate.

There is also no consensus in Taiwan about whether radiation therapy or chemotherapy should continue after surgical removal of a tumor. Liu Jung-sen notes that such an approach aims at preventing metastasis, but controversy remains due to the high cost of chemotherapy, the suffering it causes patients, and lack of evidence of its relative effectiveness. While chemotherapy is not generally favored in Taiwan, and Japanese research shows little difference in five-year survival rates, it does show higher ten-year survival rates for those undergoing chemotherapy.

According to Lai Gi-ming, "Cancer is composed of different types of cells, and chemotherapy may kill only one type. Each patient responds differently." Lai believes that in order to be truly effective, chemotherapy must be tailored the to patient and their particular type of cancer, with doctors trying different approaches and combinations.

"Currently, recurrence of lung cancer is almost inevitable," Lai says. Therefore, a major focus of future efforts will be preventing recurrence by finding a way to thoroughly eradicate lung cancer cells. To achieve this goal, according to Lai, surgical removal of tumors in the future should be followed by targeted molecular therapy to help control any undetected metastasis, and so improve survival rates.

source: Department of Health

Death Rates from Principal Types of Cancer among Women in Taiwan, 1983-2003 source: Department of Health

The road to prevention

Prevention always beats treatment, but some environmental or genetic factors will always make prevention difficult or even impossible. Even so, experts in the field continue to remind us that cancer prevention begins with daily health habits.

Aside from giving up smoking and avoiding soot and smoke, generous daily helpings of fruit and vegetables are excellent aids to cancer prevention. Lai Gi-ming points out that fruits and vegetables contain anti-cancer compounds that effectively retard the development of cancer.

Chen Chien-jen also advises members of high-risk groups (those smoking more than 20 years or aged 55 and above) to get regular screenings of lung function.

Fighting lung cancer-the number-one enemy of the Taiwanese people and the leading cause of death among women here-will require nothing less than the strictest vigilance and the utmost care in prevention.

source: Department of Health

Death Rates from Principal Types of Cancer among Women in Taiwan, 1983-2003 source: Department of Health

"Lung cancer is Taiwan's greatest enemy," says Lai Gi-ming, chief executive officer of Formosa Cancer Foundation.