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Study of Breast Cancer Risk Genes in Nigerian Women Suggests Benefits of Genetic Screening

NEW YORK (GenomeWeb) – About one in eight Nigerian women with breast cancer has inherited a genetic variant in one of four genes that predisposes her to the disease, according to a new study, and identifying such high-risk women early might reduce mortality from the disease.

Breast cancer incidence has been increasing among Nigerian women, and their tumors are more commonly triple negative and fatal than in women in the US or Europe.

As part of the Nigerian Breast Cancer Study, researchers from the US and Nigeria examined loss-of-function mutations in a panel of 25 known and suspected breast cancer genes in more than 1,000 Nigerian women with breast cancer and nearly 1,000 cancer-free women. As they reported yesterday in the Journal of Clinical Oncology, the researchers found that nearly 15 percent of patients with breast cancer in their study had a predisposing mutation. In particular, 11 percent had damaging BRCA1 or BRCA2 mutations.

"This is the first study to use high-throughput genomic analysis of African women," said senior author Olufunmilayo Olopade from the University of Chicago in a statement.

She and her colleagues added that their findings suggest genomic sequencing could be used to identify women in Nigeria who are at high risk of developing breast cancer in order to focus prevention and detection services on them.

For the study, the researchers recruited 1,136 women with invasive breast cancer and 997 women without cancer from either general hospital outpatient clinics or the community in Ibadan, Nigeria. More than 86 percent of the women with cancer were diagnosed at stage 3 or stage 4 and about half of those for whom there was data on tumor ER, PR, and HER status had triple-negative disease.

The researchers performed BROCA panel sequencing on their cohort to 250X coverage to search for loss-of-function mutations within two dozen genes, both established and candidate breast cancer risk genes.

Of the breast cancer patients, 14.7 percent carried a damaging variant in one of the genes on the panel, while 1.8 percent of the controls did.

BRCA1 mutations, the researchers noted, contributed the most to risk. Seven percent of breast cancer patients had a damaging BRCA1 mutation, and BRCA1 mutations led to a much higher chance of developing breast cancer, about 23-fold. Women with BRCA1 mutations were also significantly younger at diagnosis, 43 years on average, than other patients, who were about 48 years old on average.

BRCA2 mutations, meanwhile, were found among 4.1 percent of patients and conferred nearly an 11-fold increased chance of developing breast cancer.

Mutations in PALB2 and TP53 were also present and were associated with significant increases in breast cancer risk.

Overall, the researchers uncovered 105 different mutations in 14 genes, which they noted reflected allelic heterogeneity. At the same time, they found that about half the patients harbored a mutation that was present in at least one other case. One of the most common mutations was BRCA1 p.M1775R, which the researchers noted was the first BRCA1 mutation identified in an African-American family.

The researchers said their findings indicate that genome sequencing could be used to identify Nigerian women who are at increased risk of developing breast cancer and allocate resources to prevent or catch the disease early. "[F]ocusing risk management on genetically high-risk women could substantially reduce premature mortality from breast cancer in Nigeria," the researchers wrote in their paper.

However, they added that their study was unable to determine why triple-negative breast cancer is so much more common among Nigerian women compared to other populations. They noted that more than 90 percent of women with triple-negative breast cancer in their study had no BRCA1 mutation.