Choice Awaits Genetic Cancer Patients As Middle Age Beckons

The 32-year-old teacher had two pregnancies since she found out she had inherited a gene that contributed to her colorectal cancer, which was diagnosed in August 2020. Her first pregnancy occurred during her treatment and she had to have an abortion, while she miscarried the second one.

Knowing her window to have children is smaller than many women her age, she was relieved when she became pregnant with Sayf in March 2023. 

“The doctor advised that once I reach the target in terms of the number of children I want to have, I should have my uterus removed. Preferably before I turn 40, or around 40 as a precautionary measure,” she told Bernama.

Ever since a DNA test, taken in 2021, showed she has a very high risk of redeveloping colorectal cancer and other cancers in the future – including endometrial and ovarian cancers – Nurul Amni has been agonising over whether to do prophylactic surgery (a procedure to remove healthy tissue before they turn cancerous).

Doctors have advised her to remove the body parts that have a 60 percent chance of becoming cancerous due to her genetic cancer called Lynch Syndrome, which would reduce her chance of developing ovarian and endometrial cancer to zero. The more commonly known genetic cancer is BRCA (Breast Cancer Susceptibility Gene) 1 and 2. Treatment includes a double mastectomy and removing the ovaries before cancer.

But Nurul Amni’s struggle does not just involve her. Often, testing positive for genetic hereditary cancers can complicate things for patients like her, creating not only health implications for them but also for their families.

"You've opened Pandora's Box. So now people say because you check, then they also have to check and it causes stress (and) friction in the family," said Dr Hafizah Zaharah Ahmad, consultant oncologist at Sunway Medical Centre in Subang Jaya.

 

In 2020, Nurul Amni got married. During the honeymoon, she developed constipation, pain after eating and bloated stomach. In the space of a month, she visited her local clinic several times.

The doctor would press her stomach, causing her to hiss in pain, but he felt nothing. In the end, the diagnosis was always the same: gastritis.

“Your case is a bit odd. Every time you come, it's the same problem,” her doctor commented finally.

By this time, Nurul  Amni had noticed some blood in her stool. And the smell reminded her of her father, who had died in agony six months after being diagnosed with colorectal cancer.

She told the doctor about her father, as well as her uncle who died at the age of 35 from the same cancer.

He immediately wrote a referral letter to a specialist at a hospital for more tests.

Doctors soon found a blockage in her bowels with black spots. They diagnosed her with Stage 3B colorectal cancer, which means the cancer has grown into the bowel wall or nearby tissues, and has spread to several lymph nodes but not elsewhere.

With her family history, she soon came face to face with Dr Kavitha Rethnavelu, consultant clinical geneticist at Kuala Lumpur Hospital (HKL).

“So the red flags we see is cancer in the young. Multiple cancer, single primaries in a single person … or multiple family members with similar or related cancer,” Dr Kavitha told Bernama.

Nurul Amni agreed to do a DNA test and the results showed she had Lynch Syndrome, where one of the five genes associated with it, MLH1, has mutated. The other genes are MSH2, MSH6, PMS2 and EPCAM. These genes help repair any mistake after DNA is copied for new cells created in the body, according to the information on the Yale School of Medicine in the United States website.

As part of the guidelines, HKL offered to test Nurul Amni’s seven siblings. Three of them had Lynch, including her youngest brother, who is 17 years old. Nurul Amni said they were initially shocked but seemed to accept the results.

But so far, the results have not yielded much action among Nurul Amni’s siblings despite receiving genetic counselling from Dr Kavitha. Nurul Amni said her family was not very knowledgeable about DNA, hereditary cancers or medical treatments, preferring to go the traditional route.

“(My family in the) kampung, their knowledge of modern medicine is quite limited,” she explained, saying they had asked her to opt for traditional medicine instead of going for surgery to remove her cancer. 

She added her late father too, upon learning he had Stage IV colorectal cancer, refused all medical treatment.

Nevertheless, doctors and genetics experts say genetic counselling is a must to prepare patients for the results and their options.

“(Finding out you have inherited cancer genes like BRCA1 or BRCA2,) it's as if you're living in a stacked deck. So you really have to counsel them a lot and really do very close follow up for them because of course, at 30, they're not really ready to accept having bilateral mastectomies and removing their ovaries,” said Dr Patricia Gomez, consultant breast surgeon at Pantai Hospital.

Malaysia does not have data on the prevalence of Lynch Syndrome or BRCA, but Singapore estimates that in the republic, one out of 150 people has BRCA while one out of 530 people has Lynch Syndrome.

 

Homemaker and part-time entrepreneur Nor Haryati Rosli, 39, meanwhile, inherited the BRCA2 gene mutation from her mother, who discovered she had breast cancer at 44. Her grandmother and granduncle as well as an uncle and aunt also had cancer and died from it. 

Five years ago, Nor Haryati was diagnosed with Stage III triple-negative breast cancer in her right breast, which is rare, aggressive and difficult to treat. She has had a lumpectomy and underwent chemotherapy and radiotherapy. She also had lymph node removal surgery.

Being only 34 then, her type of cancer plus her family history rang alarm bells. Her breast surgeon referred her to the genetics department at HKL.

She tested positive for a BRCA 2 mutation, which has about 40 to 85 percent risk of contributing to breast cancer and 20 percent risk of ovarian cancer. Her younger sister and mother also tested positive. Her brother, the youngest in the family, refused to do the test.

Her cousins on her mother’s side were not very enthused either upon learning her DNA test results.

“They were not (angry with me for doing the test) but I told them how important it is to get the genetic test done,” she said, adding her relatives’ response consisted of impatient ‘okays’.

“Maybe they don’t want to accept it… sometimes people don’t want to accept things like that. They don’t have to overthink. If the illness comes, they just have to face it.”

Although Nor Haryati has finished her treatment, doctors were loathe to say she was cancer-free due to the genetic mutation.

BRCA1 and 2 genes produce proteins that repair damaged DNA and suppress tumours. A harmful mutation of either of these genes, or both which is rare, increases one’s chances of developing breast, ovarian and prostate cancers.

Nor Haryati is aware that many women with BRCA mutations opt for double mastectomy and ovary removal to reduce their risk of developing cancer to almost zero.

But being married, that was not an option for her then as she was hoping to become pregnant. Risk-reduction consists of regular monitoring for breast cancer with mammograms, and ovarian cancer via transvaginal ultrasound and blood test for cancer markers.

The problem is ovarian cancer.

Oncologist Dr Hafizah told Bernama that while mammograms are largely effective in detecting breast cancer at an early stage, it is difficult to screen for ovarian cancer as it is usually asymptomatic until much later.

She said once ovarian cancer takes root, it is hard to get rid of.

“The problem is it recurs and then after a while, the treatment doesn't work anymore. They become resistant,” she said.

Even if a patient decides to remove her ovaries then, it will still be too late. 

“It can actually come back to the same area. To the same area means not the (ovaries because) there's no ovary, but into the abdominal region. So it can be the abdominal lining. It can also come back to other organs,” said Dr Hafizah, adding removal of the ovaries is the most effective prevention strategy.

Childless and now pushing 40, Nor Haryati has to weigh her options. She is probably not going to be able to have children, so shouldn’t she do the surgery? But don’t more women have children in their 40s now? What if she was one of them?

Giving up her breasts and ovaries felt like giving up the chance for a miracle. 

“Right now, I’m just monitoring things. If it needs to be removed… well, I’m already nearing 40. I might not even have the chance to have a baby anymore. I don’t know. Maybe I’ll consider other options or prophylactic surgery,” she told Bernama via Zoom.

 

Like Nor Haryati, Nurul Amni is mostly convinced to do the surgery, but doubts persist. When she got married, she and her soldier husband Syafiq Zunnurain Zulkarnain wanted to have four children.

Questions plague her daily.

She could have the children in quick succession, but she is still technically a cancer patient due to the genetic mutation and she would not be able to handle four young children in her state. But if she removed her uterus and ovaries at around 40, she may not be able to have the family she wants. What if the kids inherit her defective genes?

And what about the effects of ovary removal? Was she ready to go into menopause at a relatively young age?

“The fear of removing my uterus is definitely there. I'm still thinking about it, still considering whether to go through with it or not,” she said, frowning. 

Then she remembers her father’s howls and groans of pain as he lay in his bed, her eyes filling with tears. She remembers her own pain when she had the blockage.

But most of all, she remembers the helplessness she felt as a 15-year-old schoolgirl watching her father suffer. Looking at her toddler son, she vows not to have her husband and child experience the same trauma.

“Because I remember, at night, hearing my father endure the pain, I cried. Because we couldn’t do anything to help. I could feel that the pain was indescribable," she said, sobbing.

"That’s why I decided to remove my uterus and ovaries. Because I think I’ve to do it so I will not be in pain.”