In a first for India, a Bengaluru woman gave birth to twins free from hereditary BRCA1 gene with the help of genetic diagnosis

By Aatika H Jain

In a breakthrough case this July, a 37-year-old woman carrying BRCA1 gene mutation, which could potentially cause breast and ovarian cancer, has given birth to twins who do not carry the mutated gene. This was a first for India. Breast cancer is the most common cancer among Indian women. In a study published in the Asia-Pacific Journal of Clinical Oncology, it was revealed that the breast cancer rate among Indian women is as high as 25.8 per 100,000 women and the mortality rate, 12.7 per 100,000 women. Breast cancer incidence in India is expected to almost double and rise to 17,97,900 by 2020.

Around 5-10 per cent breast cancer cases occur when a mutated gene is inherited; this increases the cancer risk of the individual. Among these, two-third cases happen in people with germline mutations, BRCA1 and BRCA2 mutations, which can be passed on to offspring. When Angelina Jolie announced her positive BRCA1 and BRCA2 tests and consequent preventive double mastectomy, it drew the world’s attention to inherited gene mutations potentially increasing the risk of developing breast and ovarian cancer in women, and breast, prostate and pancreatic cancer in men.

“Some forms of breast cancer and ovarian cancer are hereditary and are seen in several members of the family. This condition is called Hereditary Familial Breast and Ovarian Cancer Syndrome,” says Dr Firuza R Parikh, Director, FertilTree-Jaslok International Fertility Centre, Mumbai. “A mutation in these genes (BRCA1 and BRCA2) can predispose women to breast cancer and ovarian cancer and men to prostate cancer, colon cancer and breast cancer. Having this mutation can even cause early menopause. Hence, it is important to identify breast cancer mutations in women where there is a known history of breast cancer in the family.”

Eight years ago, Swayamprabha was diagnosed with BRCA1 mutation. Her maternal grandmother and two maternal aunts had breast cancer; her mother had ovarian cancer and maternal uncle had prostate cancer.“She was found to be heterozygous for the BRCA1 mutation (i.e. carrying 1 normal and one altered copy of BRCA1 gene). As this is an autosomal dominant condition (one altered copy of the gene is sufficient to cause disease), there was a high risk of her developing cancer and her future progeny too was at risk,” says Dr Parikh. “Having seen the devastation caused by this familial condition, Swayamprabha was convinced that the only way for her to prevent her children from suffering from this condition was PGT.”

Types of PGT

PGT is a kind of prenatal testing that is done on embryos developed using IVF technique before transferring them to the uterus. PGT has two categories—Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS). PGS is performed on the embryo cells to check for aneuploidy (missing or extra number of chromosomes) to avoid miscarriage or implantation failure. In this case, the parents have no known potential genetically inherited disorders. PGD is performed to check for a particular genetic disorder in the embryos in cases where one or both of the biological parents are in the know about the presence of that genetic disorder.

“A Mutation In These Genes (Brca1 And Brca2) Can Predispose Women To Breast Cancer And Ovarian Cancer And Men To Prostate Cancer, Colon Cancer And Breast Cancer. Having This Mutation Can Even Cause Early Menopause.”

Dr Firuza R Parikh, Director, FertilTree-Jaslok International Fertility Centre

With advancements in the field of genetics and its incorporation into Assisted Reproductive Technology, PGT has become an important tool to treat infertility as well as genetic disorders. “Swayamprabha and her husband, Debasish Panigrahi, were counselled regarding Intra-Cytoplasmic Implantation (ICSI) followed by PGT,” she says. “They are today the proud parents of twins. There are only a few hundred such pregnancies reported from all over the world and this is the first report of successful PGT for this condition in India.” Globally, PGT has been used to stop BRCA1 and BRCA2 from being passed on to the offspring in around 150 cases.

Some forms of breast cancer and ovarian cancer are hereditary and are seen in several members of the family. This condition is called Hereditary Familial Breast and Ovarian Cancer Syndrome

PGT to help with reducing cancer burden

When an individual is a carrier for a specific gene mutation, PGT helps in choosing embryos free from the mutated gene for transfer. Choosing healthy, normal embryos removes the risk of hereditary cancer due to the specific gene mutation in the offspring. This reduces the country’s cancer burden too in view of the rising cases of breast cancer in Indian women. However, this does not mean that the next generation will be totally free from other forms of cancer as it has several other aetiologies, says Dr Parikh. PGT can be utilised to identify approximately 2,000 known genetic disorders. “The condition could be present either in both the parents (recessive condition) or in one of the parents (dominant condition). There are also many disorders which are sex-linked,” says Dr Parikh. The cost of PGT has almost halved in the past five years to around INR 15,000-INR 20,000 per embryo. It not only improves the chances of a successful pregnancy in IVF procedures but also helps in putting a stop to passing on hereditary genetic disorders. It is also recommended in IVF cases when the woman is 38 years or older. Swayamprabha’s free-from-hereditary-oncogene twins give hope for disease-free children to innumerable people with similar medical conditions. This is just the beginning of hope for lakhs of people WCS