Largest study of BRCA1 and BRCA2 carriers refines cancer risk estimates in Asian populations

Singapore Genome by STAR, a team of clinician-scientists and scientists from the University of Nottingham (Malaysia Campus), National Cancer Center Singapore (NCCS), Malaysian Cancer Research Centre, Nanyang Technological University Singapore (NTU Singapore), University of Malaya, and University of Cambridge A* The Institute for Breast Cancer (GIS) and other institutions conducted the largest study ever conducted on BRCA1 and BRCA2 (breast cancer genes 1 and 2) carriers in the Asian population, determining the prevalence of breast and ovarian cancer in this population. We have refined our risk estimates. The survey results are Lancet Community Medicine – Western Pacificcan better guide the clinical management of Asian patients with BRCA1 and BRCA2 mutations.

Breast cancer is the most common and leading cause of cancer death among women in Singapore, while ovarian cancer ranks sixth.^th Changes in incidence and mortality rates for the same group. A 2022 study conducted as part of Singapore's National Precision Medicine Program found that almost 1 in 150 Singaporeans are affected by genetic mutations associated with hereditary breast and ovarian cancer. Shown. Global estimates indicate that 3-5% of breast cancers and 10-15% of ovarian cancers are caused by mutations in these genes. The BRCA1 and BRCA2 genes are the most commonly affected genes in hereditary breast and ovarian cancers, and carriers are at increased risk of developing these cancers.

However, large-scale studies of BRCA1 and BRCA2 carriers have only been conducted in populations with predominantly European ancestry. Given that other genetic and lifestyle factors also influence cancer risk in BRCA carriers and that these differ in Asians compared to Europeans, the There was significant uncertainty. The clinical management of her BRCA1 and BRCA2 carriers in Asia may improve, as only four small studies have been conducted on this cohort to date. More information is needed to guide preventive care and monitoring for BRCA1 and BRCA2 carriers of Asian descent.

To address this pressing clinical need, a multidisciplinary team of clinicians, scientists, scientists, and genetic counselors studied clinical data from 572 families in Singapore and Malaysia with BRCA1 and BRCA2 mutations . The families ranged in age from 20 to 79 years old and were of Chinese, Indian, and Malay descent. Of the 1,121 BRCA1 carriers, 144 were diagnosed with breast cancer and 65 with ovarian cancer. of 1,275 BRCA2 Carriers, 152 people diagnosed with breast cancer and 19 people have ovarian cancer. Statistical analysis was used to estimate the risk of carriers developing breast and ovarian cancer. Comparisons were also made based on ethnicity, location, and birth cohort.

Main findings

The findings show that the penetrance, or chance of developing breast cancer, for these carriers has increased over time, with those born after 1960 seeing the greatest increase. I did. This increase is likely driven by urbanization and changes in reproductive patterns. Estimated breast cancer incidence rates for all ethnicities studied were highest at age 55 and decreased thereafter.

The study also highlighted that the incidence of cancer in BRCA1 and BRCA2 carriers in Singapore is similar to that in Western populations. The blue line, blue circle, and blue square represent the cumulative risk for Asians in the United States, Malaysian Chinese, and Singaporean Chinese, respectively; the orange line, orange circle, and orange square represent the cumulative risk for Asians in the United Kingdom; It represents Malaysian Indians and Singaporean Indians. Each.

The cumulative risk of developing breast and ovarian cancer among Chinese BRCA1 and BRCA2 carriers in Singapore was similar to Asians in the United States (approximately 37% East Asians in the United States) but compared to Chinese in Malaysia. Then it was expensive. The cumulative risk of BRCA1 and BRCA2 carriers among Indians in Singapore was similar to that among British Asians (approximately 47% South Asians in the UK), but higher compared to Indians in Malaysia.

Implications for clinical management

The results of this study provide an important new framework for estimating cancer risk in Asian carriers and allow for a more appropriate approach to the clinical management of this population. This is supported by an editorial in the February 2024 issue. JAMA Oncology, advances in technology have made it easier and cheaper to identify BRCA1 and BRCA2 carriers and implement cancer risk management strategies outlined by the National Comprehensive Cancer Network (a coalition of 33 cancer centers in the United States). was of the opinion that it would be possible. This includes a clinical breast exam and breast MRI at age 25, a mammogram at age 30, and risk-reducing surgery and therapeutic intervention. In the same issue, a study of 2,488 women in North America and Europe found that MRI surveillance in women who were BRCA1 carriers was associated with a significant reduction in breast cancer mortality compared with no MRI surveillance. It was suggested that A second study of 4,332 women who were BRCA1 or BRCA2 carriers showed that oophorectomy was associated with a significant reduction in all-cause mortality.

Early intervention for BRCA1 and BRCA2 carriers includes individual risk-based screening options to detect cancer at its earliest and most treatable stages, as well as therapeutic interventions (e.g., anti-estrogen therapy, tamoxifen) and preventive surgery. This includes risk reduction measures such as (mastectomy, salpingectomy, etc.). , ovariectomy).

A recent study shows that carriers of the BRCA1 and BRCA2 genes are more common than previously thought, but the study found that carriers in Singapore are at increased risk of developing breast and ovarian cancer. It highlights that it is as high as other countries. Genetic testing should be considered to identify carriers early, and care plans should be individualized so that early interventions such as regular monitoring and risk mitigation measures can be implemented. ”

Joanne Ngeow, co-senior author, Associate Professor of Genomic Medicine, Lee Kong Chian Medical School, NTU Singapore, and Head of Cancer Genetics Services, NCCS

This research is supported by the National Medical Research Council (NMRC) of the Ministry of Health, Singapore under the Clinician Scientist Award – Investigator (MOH-000654).