The frequency of known germline LGR4 missense variant in the ethnic groups of West Siberia.

Background: Hereditary breast cancer is an autosomal dominant disease caused by variants in genes such as BRCA1/2, RAD51, ATM, BRIP1, and others. In a previous study using whole exome sequencing, we identified a germline variant of the LGR4 gene (rs34804482, NM_018490.5(LGR4):c.2531 A > G (p.Asp844Gly)) in a young Tuvan breast cancer patient (belonging to the Turkic-speaking tribes of Central Asia). The aim of this study was to determine the frequency of the variant of the LGR4 gene NM_018490.5(LGR4):c.2531 A > G (p.Asp844Gly) in ethnic groups of West Siberia using the PCR-RT method.

Methods: The study involved 735 breast cancer patients from ethnic groups in Siberia, median age at diagnosis of 43 ± 15.6 years. The control group consisted of 727 healthy women from Siberia, median age of 43.05 ± 13.5 years.

Results: The frequency of this variant (rs34804482) was 0.015 in Russian, 0.022 in Buryat, and 0.069 in Tuvan breast cancer patients. In Tuvan women with breast cancer, the frequency of the LGR4 gene variant was significantly higher than in Russian BC patients (0.069 versus 0.015, X² = 8.153, p = 0.005). The frequency of the LGR4 gene variant (rs34804482) in healthy Tuvan women was significantly higher than in healthy Russian women (0.066 versus 0.016, X² = 6.368, p = 0.012). The variant frequency in healthy Russians was close to that in Europeans (0.016 versus 0.0219).

Conclusions: We found no statistically significant differences in the rs34804482 frequency between breast cancer patients and healthy individuals in the ethnic groups studied. The highest frequency of this missense germline variant was observed among Tuvans.