Cancer breakthrough: Mumbai study finds gene markers that could help early detection

Researchers in Mumbai have made a breakthrough discovery that holds the potential to provide a screening tool for breast and ovarian cancer in Indian women. By a happy coincidence, the discovery has come in October, which is celebrated as breast cancer awareness month by major charities across the world.

 Dr Pravin Potdar, head of the department of molecular medicine and biology at Jaslok Hospital and Research Centre, has zeroed in on founder mutations in breast-cancer-causing genes BRCA1 and BRCA2 which are found only in the Indian population.

The founder mutations hold the potential to act as biomarkers for breast and ovarian cancer patients, which can be used to develop a tool for prior screening in vulnerable individuals.

A biomarker, or biological marker, is a substance that is used as an indicator of a biological state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses. In genetics, a biomarker is a DNA sequence that causes disease or is associated with susceptibility to disease.

“Such biomarkers are already in use for investigating individuals who are at high risk for developing coronary heart disease, prostate cancer, and lung cancer (preliminary test), and breast cancer will soon join the league,” Dr Potdar said.

This means oncologists may soon be able to assess the risk that a woman may develop breast cancer with a simple blood test using the biomarkers outlined in the study.

Breast cancer is the second most prevalent cancer among Indian women. In India, on an average, 80,000 women are diagnosed with breast cancer and 40,000 women die of the disease every year in the age group of 30-70 years. The incidence of breast cancer in India has increased rapidly due to changes in lifestyle coupled with lack of awareness about the disease.

Over the past two decades, the genes BRCA1 and BRCA2 have been identified and associated with every heightened risk of breast and ovarian cancer.

“In the Indian context, many researchers from various parts of the country have worked on BRCA1 and BRCA2 mutations, and they have reported a number of mutations in BRCA1 and BRAC2 genes,” said Dr Potdar.

“But nobody had so far established any specific founder mutation and genetic profile of the Indian population with respect to BRCA1 and BRCA2 which could be used as a biomarker for monitoring of breast and ovarian cancer.”

Dr Potdar and his colleagues initiated the programme two years ago and sequenced the entire BRCA1 and BRCA2 genes of normal individuals as well as in patients of breast and ovarian cancer.

The researchers analysed 24 functional gene fragments (exons) in BRCA1 and 27 in BRCA2 to compare the differences in the sequences (polymorphism) between normal individuals and patients of breast or ovarian cancer using DNA sequence analysis.

“We are the first to report five polymorphism spots in BRCA1 gene and three in BRCA2 genes in Indian normal, breast and ovarian cancer patients,” said Dr Potdar.

The database of the National Centre for Biotechnology Information (NCBI), a branch of the National Institute of Health (NIH), has reported complete gene sequences of BRCA1 and BRCA2, which feature as a standard for worldwide comparison.

“This study elaborates the importance of the database to define exact polymorphisms and mutation spots of breast or ovarian cancers, to develop programmes for monitoring breast-cancer risk in new generation of the Indian population,” said Dr Potdar.

After establishing polymorphisms in the Indian population, the research team led by Dr. Potdar scanned almost 34 families (125 individuals) who were first-degree relatives of breast-cancer patients, 40 sporadic patients (patients with no family history of breast cancer), and 25 normal individuals for BRCA1 and BRCA2 gene mutations

Novel mutations were found in both sporadic and familial breast- and ovarian-cancer patients, indicating that the mutations were associated with the cancers in the Indian population irrespective of family history, and thus could be used as biomarkers for early detection of breast cancer in younger generations having a family history, and to monitor individual women for risk of breast cancer.

“This is the first report to show global founder mutational spot which indicates the cause of breast or ovarian cancer in affected individuals as well as among family members,” explained Dr Potdar.

“A woman’s risk of developing breast cancer is two or more times greater if she has a first-degree relative who has developed the disease before the age of 50.”

The study holds out the prospect of early detection of breast and ovarian cancers, which, in turn, will help early diagnosis and treatment.