Investigation on the clinicopathological characteristics and BRCA1/2 gene variation of patients in breast cancer pedigrees in Northern Henan Province
Authors: Zhao Hui , Wang Lei , Feng Yueqing , Yang Junzheng 
Published: May 2023

AbstractObjectivesTo investigate the clinicopathological characteristics of breast cancer patients and the pathogenic gene variation of BRCA1/2 in breast cancer pedigrees in Northern Henan province, to provide the evidences for treatment or prevention of breast cancer.Methods214 breast cancer patients from different families admitted to Xinxiang Central Hospital/Fourth Clinical College of Xinxiang Medical University from November 2018 to January 2021 were selected, DNA samples were extracted from patient and the exon and intron splicing regions in the coding sequences of BRCA1 and BRCA2 genes were amplified by PCR, the amplified products were screened and the abnormal segments were confirmed by Sanger sequencing; finally, Integrative Genomics Viewer software and Codon Code Aligner software was used to verify the candidate pathogenic sites in breast cancer pedigrees.ResultsAmong 214 cases of breast cancer patients, there were 177 patients with unilateral breast cancer and 37 patients with bilateral breast cancer, accounting for 82.71% and 17.29% in 214 breast cancer patients, respectively; there were 122 patients in premenopausal menstruation and 92 patients in postmenopausal state at the time of diagnosis, accounting for 57.01% and 42.99% in 214 breast cancer patients, respectively; there were 137 patients with the tumor diameter at 2-5 cm, 60 patients with tumor diameter≤2 cm, 17 patients with tumor diameter>5 cm, accounting for 64.02%, 28.04%, and 7.94%, respectively; there were 183 patients were invasive ductal carcinoma, accounting for 85.51% in 214 breast cancer patients; regional lymph node metastasis was mainly negative (130 cases, accounting for 60.75% in 214 breast cancer patients), TNM staging was mainly stage II (138 cases, accounting for 64.49% in 214 breast cancer patients), and histological classification was mainly stage II. The gene sequencing results demonstrated that a total of 20 pathogenic mutations were found including 17 BRCA1 gene mutations and 3 BRCA2 gene mutations in 214 patients with familial breast cancer; there were 11 frameshift mutations, 3 nonsense mutations and 3 splice mutations in 17 cases BRCA1 gene mutation, and all 3 BRCA2 gene mutations were frameshift mutations; especially, the 1100delT site mutation of BRCA1 gene was repeated in 3 patients with breast cancer. 18 high frequency SNP (frequency ≥ 5%) loci were found in 214 breast cancer patients, there were 17 the mutation frequency was higher than that of the normal population; especially, the mutation frequency of rs799917 is lower than that of normal population. Finally, we analyzed the clinical characteristics of rs80356892 polymorphism carriers in 214 breast cancer patients, found that there were 5 patients with rs80356892 mutation, including 3 patients with bilateral primary breast cancer, accounting for 60%, and the 5 patients with rs80356892 mutation had the family history of disease.Conclusionthe clinicopathological characteristics and BRCA1/2 gene variation of patients in breast cancer pedigrees in Northern Henan Province had certain specificity and regional characteristics, these data may provide some useful information for prevention or treatment for breast cancer.