A person with certain genetic mutations is guaranteed that he will get the disease. In the second of a three-part series, MYB looks at how DNA testing has allowed defective genes to be identified so that drastic measures can be taken to avoid cancer
Ms Felicia Lee had her entire large intestine, or colon, removed when she was 15 years old – so she would not develop cancer there. She inherited a faulty gene from her father that would definitely cause her to develop colorectal cancer – or cancer of the colon and rectum – in her 20s or 30s. Now 28 years old, she remains free of cancer. So does her younger sister, 26, who also inherited the faulty gene and had her colon removed. They had been diagnosed 16 years ago after their father developed colorectal cancer. Now a 54-year-old carpenter, he went for surgery and is on long-term medication to keep part of the tumour, which had spread beyond the colon and could not be removed, in check.
Genetic tests have helped to diagnose people like the Lees, who have inherited specific mutated genes that have been shown to have a strong link to certain types of cancer, mainly colorectal, breast and ovarian. Often, they are asked to take the test after they and/or two or three family members have developed cancer at a fairly young age, typically below the age of 50.
A genetic test checks for a specific gene or mutation in the gene by looking at its components such as deoxyribonucleic acid (DNA) or chromosomes (bundles of DNA); or sometimes for substances such as proteins produced by the gene or mutation. Usually, all that is needed is a blood sample.
A public hospital charges about $2,000 to $3,000 to search for a gene mutation in a patient who has colorectal, breast or ovarian cancer at a young age or has a strong family history of related types of cancer. Once the mutation has been found, each subsequent family member can be tested for that mutation, at about $300 each. When mutated genes have been identified, precautions can be taken to keep cancer at bay or to catch it early, thereby saving the lives of their carriers. Fortunately, the mutations do not occur often.
For example, Singapore General Hospital (SGH) has performed only 330 genetic tests for specific mutated genes linked to heritable colorectal cancer since it began doing these tests in 1989. That year, it started the Singapore Polyposis Registry to monitor families diagnosed with these faulty genes, or with a very strong family history of colorectal cancer. The registry now has 233 families diagnosed with four known genetic conditions that can cause colorectal cancer, and 169 other families with a strong history of the cancer, but no known abnormal genes identified yet.
INHERITED COLORECTAL CANCER
The Singapore Polyposis Registry has 233 families diagnosed with four known genetic conditions that can cause colorectal cancer. Of these, 89 families, including Ms Felicia Lee and her family, have been diagnosed with a condition called familial adenomatous polyposis. Those with this condition have a mutation in the adenomatous polyposis coli gene, which normally prevents cells from growing uncontrollably and causing cancer.
The mutation impairs the gene’s ability, resulting in thousands of abnormal growths called polyps sprouting in the colon, and sometimes also in the small intestine. The polyps are initially benign, but will turn cancerous over time if left untreated. About 2 to 5 per cent of all colorectal cancer cases are caused by this condition. The test involves extracting and analysing DNA, which makes up genes, from a sample of blood.
Those who are diagnosed with the faulty gene usually have colonoscopy and gastroscopy every other year. Once polyps are spotted in the colon, the patients are advised to have the colon removed, which cuts the risk of developing colon cancer to zero, said Dr Koh Poh Koon, director of colorectal cancer genomic health services at SGH. They are still at some risk of developing rectal cancer and duodenal cancer (cancer of the small intestine), so they will still need a gastroscopy every other year.
Another condition, the Lynch syndrome, which affects 132 families in the registry, results from mutations in any of five genes. Those with the syndrome have up to an 80 per cent risk of developing colorectal cancer. It accounts for about 5 to 8 per cent of all colorectal cancer cases. Patients go through regular colonoscopy and any polyps – which do not grow in large numbers for those with this syndrome – are removed.
INHERITED BREAST CANCER
Ms Lee, 28, had her colon removed at 15, before she had cancer. She now leads an active life and is cancer-free. Besides colorectal cancer, the other cancer with a strong link to specific faulty genes, and screened for in high-risk patients, is breast cancer. Those with a mutation in the breast cancer 1 (BRCA1) gene have a 60 to 80 per cent risk of developing breast cancer in their lifetime, while those with a mutated breast cancer 2 (BRCA2) gene have a 40 to 60 per cent risk, said Dr Wong Seng Weng, medical oncologist at the Singapore Medical Group.
Together, they account for about 5 per cent of all breast cancer cases. People with either of the faulty genes also have a 40 per cent risk of suffering from ovarian cancer in their lifetime, Dr Wong added. The good news is that these mutations are rare, occurring in about 0.1 per cent of women. But as the risks to the women with the mutations are high, they are strongly recommended to have both their breasts removed, said Dr Lee Soo Chin, senior consultant at the department of haematology-oncology of the National University Cancer Institute, Singapore.
This precaution will reduce the risk of breast cancer by 90 to 95 per cent, she said. But as this is very mutilating, fewer than 20 per cent of patients take this up, she said. The others will need annual mammograms to pick up any breast cancer early. The pre-emptive removal of the ovaries is also recommended and is usually more acceptable to patients, Dr Lee said.
LEADING A NORMAL LIFE
Taking genetic tests to see if one has mutations that cause cancer is not just about preventing the disease. It is also about having peace of mind and cost savings for those who do not carry the mutation despite having a strong family history of colorectal or breast cancer, doctors said.
For example, a woman with a family history of a BRCA mutation who does not carry the gene will need to go for regular mammograms only from the age of 40 like other women, rather than every year from, say, her 20s, said NUH oncologist Lee Soo Chin. The preventive measures, while drastic in some cases, need not have a permanent impact on the quality of life, doctors said. For example, patients who have their colons removed have to carry a stoma bag outside their body into which their waste empties for only about three months. They have a second operation to join the small intestine to the rectum and are able to live fairly normal lives afterwards.
SGH Surgeon Koh Poh Koon said: “They may have to go to the toilet a bit more often than others. Most patients are fairly young and their bodies can adapt well.” Ms Felicia Lee, 28, who had her colon removed 13 years ago, went back to school just two weeks after her first operation and played basketball mere weeks after her second operation. For the first few months, she had to go to the toilet 18 times a day, but her body adapted and life went back to normal in a year. Now, she plays basketball, goes to the gym and practises yoga. She has a check-up every year.
Ms Lee, who is in between jobs, said: “When I was diagnosed at 12, I decided how I would deal with it. It’s family history, I can’t blame anyone. I thought about how to get treated to live longer. I don’t want to give up my life. If I had not gone for the genetic test, I would not have known that I had such big polyps in my colon. I could have developed cancer and died by now.”