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Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants

Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants

Authored by: George M. Pikler, M.D., Ph.D., FACP

All of us have two active copies of BRCA1 and BRCA2 genes located on chromosome 17 and chromosome 13 respectively. Both normally act as tumor suppressors – they help to regulate cell division keeping our genome healthy and intact. DNA damage which is a common occurrence in daily life (UV light, ionizing radiation, replication errors, chemical agents, etc.) can result in single and double strand breaks in the DNA structure which must be repaired for cell survival.

BRCA derived functional proteins repair damaged DNA. These proteins play an important role in maintaining cellular genetic integrity, they regulate cell growth and prevent abnormal cell division and development of malignancy. BRCA1 and BRCA2 gene mutations predispose an individual to develop malignant tumors.

BRCA mutations can either be inherited (germline) and present in all individual cells or can be acquired and occur exclusively in the tumor cells (somatic). The majority of BRCA1 and BRCA2 aberrations are the result of somatic mutations.

Pathogenic Variants (PVs) in BRCA1 and BRCA2 (BRCA1/2) are well known to be associated with increased lifetime risk for breast and ovarian cancer in women with risk estimates as high as 85% and 40% respectively.

In a recent study1 PVs in BRCA1 were significantly associated with increased risk for biliary tract, gastric and pancreatic cancers in addition to female breast and ovarian cancer. PVs in BRCA2 increased risk for both female and male breast, gastric, ovarian, pancreatic, prostate, and esophageal cancers.

The NCCN recommend breast and ovarian screening for BRCA1/2 carriers, prostate cancer screening for BRCA2 carriers. Screening is also recommended for pancreatic cancer in BRCA1/2 carriers, but only in the presence of a positive family history of the disease.

In light of the above findings, it would be advisable to screen for BRCA1/2 carriers in patients with the additional malignancies reported in this study.

1Momozawa Y, Sasai R, Usuai Y, et al. JAMA Oncol. 2022 Apr 14

Authored by:
George M.Pikler, M.D., Ph.D., FACP
Lead Oncology Advocate N1X10

Dr. Pikler graduated summa cum laude from the Central University of Ecuador School of Medicine in 1968. His postdoctoral training included an internship in internal medicine at Greater Baltimore Medical Center in Baltimore, MD, a residency in internal medicine and a doctoral degree in molecular medicine at the Mayo Clinic in Rochester, MN. The American Cancer Society awarded him a fellowship in medical oncology and hematology at M.D. Anderson & Tumor Institute in Houston, TX.

With training certifications in internal medicine and oncology, Dr. Pikler and his family moved to Tulsa, OK where he established and was the President of Cancer Specialists, Inc, a boutique oncology-hematology clinical research private practice. In addition, he was the chief of the oncology at Hillcrest Medical Center, a teaching hospital for 20 years and associate professor of medicine, oncology-hematology at the University of Oklahoma, Tulsa Medical College. He was one of the founders of the Southern Association of Oncology Practices and subsequently the National Medical Director for the International Oncology Network, AmerisourceBergen’s Oncology Division.

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