Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women.

BACKGROUND

The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.

AIM

To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.

METHODS

We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020. Data was collected and analyzed on Excel sheet.

RESULTS

In total, 358 individuals were included, including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer. The prevalence of pathogenic variants was 8.63% (19/220) in patients with breast cancer, and 15.1% (5/33) in those with ovarian cancer. Among the 25 of 220 patients with breast cancer tested by next-generation sequencing, 3 patients had pathogenic variants other than . The highest risk was observed in those aged 40 years with breast cancer and a positive family history, where the prevalence was 20.1% (9/43). Among the unaffected subjects, 31.1% (14/45) had the same pathogenic variants in their corresponding relatives. Among the subjects referred because of a positive family history of cancer without known hereditary factors, 5.35% (3/56) had pathogenic variants of and . The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a pathogenic variant.

CONCLUSION

This study showed a 8.63% prevalence of pathogenic variants in patients with breast cancer and a 15.1% prevalence in patients with ovarian cancer. Among the relatives of patients with pathogenic variants, 31% tested positive for the same variant, while 5.3% of subjects who tested positive due to a family history of breast cancer had a pathogenic variant.