Cancer cells are a mutation from a normal cell. This is a multistep process, in which many mutations accumulate. In general, mild dysplasia occurs first, and then moderate and severe dysplasia. It then further develops into carcinoma in situ (CIS), which takes several years to decades (Figure 4). The precancerous process varies in different cancers, for example, it takes 6-10 years from cervical adenocarcinoma in situ Level I to Level III. It may be 14-18 years from breast dysplasia to ductal carcinoma in situ. The formation of colon adenoma takes 5-20 years, and further development to cancer needs 5-15 years; there will be more than a 30-year chronic process before prostate cancer; smokers who had lung cancer have an incubation period of 20-40 years. It generally takes about 20 years to develop esophageal cancer, bladder cancer and head and neck tumors; the formation of non-melanoma skin cancer may experience 40-50 years.
Figure 4: Roughly the time required for the whole process from the development of precancerous lesions to carcinoma in situ and to invasive cancer. CIN: Cervical Intraepithelial Neoplasia; CIS: carcinoma in situ; DCIS: ductal carcinoma in situ; TIS: transitional cell carcinoma in situ (Quoted from Nature Cancer Review 15 Nov 2012)
Once cancer cells and a tangible tumor are clinically formed, there are probably 109-1010 cancer cells. The elapsed time of tumors or the same tumor in different people is not the same.
If cancer cells divide once every four weeks, meaning one cell turns into two cells, and then four cells after 12 weeks, by this analogy, there are about 4,000 cancer cells after one year and the number of cancer cells will reach more than 1 million after two years. The cancer cell is small, 100,000 cancer cells can just be seen by naked eyes and the size of one million is as large as a needle. When cancer cells reach to 1 billion, the size of the tumor could be as large as a grape, which can be seen on an ultrasound and CT scan. If the tumor reaches a golf ball-size and the number of cancer cells is 100 billion, generally it takes about three years. Clinically, if the tumor grows as large as a watermelon and weighs more than 1 kg, this kind of tumor has been growing for at least 4 to 5 years (Figure 5).
Pancreatic cancer is considered a cancer with poor prognosis, metastases is the main cause of death. But even though this is such a vicious cancer, when it starts it's not so fierce. According to a research article from John-Hopkins University published in 2010 in the influential journal Nature, the author had studied the primary and metastatic pancreatic cancer genomics and found that it takes at least 10 years from a cell mutation to develop into a non-metastatic cancer cell. It needs another five years for cells to acquire cancer metastasis ability, after that patients will die of that cancer disease in about two years.
My liver tumor was about the size of a walnut when I had my operation, there could have been billions of cancer cells. From 1998 when an ultrasound discovered the “hemangioma” eight years had passed. It seemed that my cancer had grown relatively slowly. Due to this slow growth, after the PET-CT scan showed my “red” lesion, I concluded, with my expertise, that I had “cholangiocarcinoma” because only such a cancer grew slowly in the early stage.
I reflected: Could my cancer have been discovered earlier? Even then, is it early enough to predict I could have cancer?
Shortly after my surgery in February 2006 a friend from the Shanghai medical community, a renowned medical expert called me and said, “Five to six years ago I looked at your palm and predicted that after five years you would have a “Kan”. “Kan” is a Shanghainese word meaning I would meet with misfortune, most likely this would be disease. I was shocked because this friend had also made a prediction about a famous physician in Shanghai who was also one of my respected teachers. This physician suffered from cancer, had an operation
and recovered well. But my friend suddenly predicted that his condition would become life threatening. As predicted, three days later, the physician’s condition suddenly deteriorated; two weeks later he passed away. Therefore his predictions were regarded as somewhat of a “myth” in Shanghai. “Could I survive?” I asked him, giving him my palm to read. “If I was still alive after five years, I would live to over 83 years old.” Now it is over six years after my surgery, I hope he's right.
So far I’m not convinced about the secret of palm reading to predict disease. I have several books on palmistry, one author of those books is a famous professor of the University of Traditional Chinese Medicine. But I still cannot learn where the “secret” lies. Some people say that the Chinese classic “Book of Changes” is profound, which explains fortune-telling, I have also read it but I'm still confused.
Nowadays, the human genome has been cracked, “Fortunetelling” is likely to turn into a reality (Figure 6). In the U.S., there are many companies specialized in genome measuring to predict disease. One of Google’s founders, Sergey Brin’s wife, Anne Wojcicki set up a gene sequencing company with a peculiar name, called 23 and Me. 23 refers to the 23 pairs of human chromosomes. Sergey Brin was one of the first to receive the whole genome sequencing test. The result showed that he had a higher risk for certain diseases and lower risk for
others. He was pleased that it was “insignificant”. But his wife asked him to test the LRRK2 gene, if this gene mutates, it would illustrate an increased risk of suffering from Parkinson's disease. The result showed that he had such gene mutations and would therefore have a 74% possibility of suffering from Parkinson's disease by the age of 80. In fact, his mother had suffered from the disease in early years, and she was also a mutant gene carrier. Brin was not upset or scared, he said that he would be more appreciative of life and support the research
of Parkinson’s disease.
Figure 6 Gene is on the DNA helix. Genomic test can predict diseases, including cancer risks.
I’ll introduce another gene “fortune-telling” story. Jeffrey Guerche, a chief expert of a genetic company volunteered to experience the company’s own DNA test when he was 48 years old. The results showed that his risk of suffering from prostate cancer was 1.9 times that of others, which made him vigilant as his father also suffered from prostate cancer at 68 years old. He undertook the prostate-associated antigen PSA test and no abnormality was found. He had a prostate ultrasound and ultrasound-guided prostate biopsy. Cancer cells had been found on 3 out of 12 tissue samples. He underwent a radical prostatectomy. Although this was an unfortunate thing, he was lucky to have early detection because the prognosis of early stage prostate cancer is quite good.
Let me give another example. Francis Collins, introduced earlier as, the director of the human genome project and the director of American National Institutes of Health (NIH) put himself as a guide of the new era of personalized medicine. He respectively sent his own DNA samples to three DNA analyst companies in America as an ordinary customer. The results showed that he is more likely to suffer from type 2 diabetes, macular degeneration and a special-type of glaucoma. Whilst his aunt went blind at 80 years old; the possibility for him to suffer from prostate cancer is 40% higher than the average person, which his father suffered from in his later years. He also found himself the recessive gene carrier of two diseases, 1- antitrypsin deficiency and hemochromatosis. The former one will lead to emphysema or liver disease and the latter can lead to cirrhosis, heart failure and diabetes. Although he will not have these two diseases, his children have a higher risk of suffering from them.
Could these three examples listed above be spread to all people? The “UK BioBank Project” is making assessments on genetic risk factor and medical information of 5,000,000 individuals. In the next five years, a whole genome sequencing test may decrease to below $1,000. I believe that, “Genes telling your Fortune” will be accepted by the community sooner or later as an established healthcare concept, at least by the highly educated. Since environment plays an important role in the occurrence of disease, changing the environment and lifestyle can help reduce or avoid the occurrence of disease, especially when you know which disease types you may be prone to. When Francis Collins knew his sequencing results, his lifestyle underwent significant changes, including controlling diet, increasing physical activities, eating more fish, an aspirin per day, drinking red wine and regular medical examinations, sincerely hoping these “fated diseases” would occur as late as possible.
I thought over my cholangiocarcinoma, had it been possible to predict? In the past ten years, it was nearly impossible to apply gene sequencing technology to predict diseases, but now it has turned into a reality. In recent years, China’s genetic testing has made huge leaps in progress. Two milliliters of saliva is collected as a sample. Mass information (900,000 loci) will be detected by applying the specific for Asian high-flux zhonghua8 chip, then applying the RGTD Database, Data Analysis System and International Risk Assessment Algorithm
to analyze genetic data, which can quantitatively predict 91 kinds of diseases in 8 categories. The detection rate is 99%, and accuracy rate is 99.9%. Among them, 24 kinds of cancers can be predicted (Table 1).
Some wise people, especially those who have a family history of cancer (in fact, the majority of families have someone with cancer), should keep highly vigilant against cancer. If the test could be included in routine physical examination, it would be a perfect health management tool (Table 2). It would be best for family members of breast cancer patient to detect BRCA1/2 mutations, and to detect MLH1, 2, 3 mutations for family members for colon cancer patients. In the United States, genetic tests and preventive treatments have dropped the incidence of female breast cancer by 70%, and the incidence of colorectal cancer has decreased by 90%.
China is one of the countries in the world to participate in the human genome sequencing test, keeping pace with technological developments. By applying the high-throughput microarray gene microchip technology and collecting 2 ml of saliva (figure 7), the human genome can be measured. Further utilizing this special data analysis system, a quantitative risk assessment on more than ninety types of disease for eight categories can be made. It can also point out over thirty individual characteristics and 120 kinds of conditions in twelve
categories commonly applied to drug safety. The average detection rate is 99% with an accuracy rate of >99.9%.
Recently, I received a whole genome sequencing test, the results revealed I had a higher possibility of developing several diseases, one of which is cancer. My risk of other diseases is about the same as the general public’s, I felt reassured. Good results made me happy while the bad one made me keep vigilant. The test results also suggested that I have a higher IQ, curiosity and perseverance. Regardless of their accuracy, I did feel encouraged and comforted. My whole-genome sequencing test results were copied in a CD-ROM, which will stay with me for a lifetime, because genes inherited from parents will never change.