Breast cancer is the most commonly diagnosed type of cancer and cause of cancer death among Hispanic women.1 Hispanic women are also more likely than white women to be diagnosed with the disease at a later stage, which makes it more difficult to treat.2 Moreover, limited access and other barriers prevent ethnic minorities from undergoing genetic testing,3 which may contribute to the cancer burden in these populations. 

Research on genomic predisposition to breast cancer among Hispanic women and other diverse groups has been scarce. Studies that have examined the predisposition in these groups tended to focus on BRCA mutations.4

Now, a new paper sheds light on a variety of other relevant mutations in Hispanic women,5 and another recent study investigates this question in this and other diverse populations.6

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In the first study, researchers looked at data for 12 known and suspected breast cancer susceptibility genes in Hispanic women with familial breast cancer who had tested negative for BRCA mutations.5 The investigators performed whole-exome sequencing on DNA from 1054 Hispanic women with familial breast cancer and 312 Hispanic controls from Southern California. The investigators also included whole-exome sequencing data from 887 multiethnic cohort controls who identified as Hispanic.

After analyzing the data, the investigators looked at the spectrum and frequency of pathogenic variants (other than BRCA) in known breast cancer susceptibility genes. The researchers found that 3 recurrent pathogenic variants represented 52% of the total mutations. One recurrent PALB2 pathogenic variant was responsible for 50% of all PALB2 variants. The researchers also identified a recurrent CHEK2 pathogenic variant, c.707T>C; pL236P, that was observed 14 times, and represented 70% of CHEK2 pathogenic variant carriers in the study. This variant had been previously listed 5 times as a variant of uncertain significance and once as likely benign in the publicly available database ClinVar. 

In 2017, the molecular diagnostic company Myriad Genetics distributed revised reports that reclassified the variant as likely pathogenic. In the new study, the authors were “able to show that it’s pathogenic with great confidence statistically, and that the magnitude of the risk is comparable to the founder mutation of European origin that most of the literature is based on,” said lead study author, Jeffrey N. Weitzel, MD, a professor of oncology and population sciences at City of Hope Cancer Center, Duarte, California.