Profiling of the germline mutation BRCA1: p.Ile1845fs in a large cohort of Han Chinese breast cancer

Abstract

BackgroundBreast cancer is a one of the malignant carcinomas partially caused by genetic risk factors. Germline BRCA1 gene mutations are reportedly associated with breast cancers. Identification of BRCA1 mutations greatly improves the preventive strategies and management of breast cancer. The aim of our study was to investigate the frequency of the deleterious BRCA1: p.Ile1845fs variant in breast carcinomas, as well as the correlation between p.Ile1845fs variant with clinicopathological parameters and clinical outcomes.ResultsA total of 23,481 clinically high-risk patients with breast cancer and 6489 healthy controls were recruited for p.Ile1845fs variant sequencing (either sanger or next generation sequencing). We identified 94 breast cancer patients (0.40%, 94/23481) as well as 11 healthy controls (0.17%, 11/6489) carried p.Ile1845fs variant. BRCA1: p.Ile1845fs variant showed a higher frequency in patients with TNBC molecular typing (20.21%, 19/94) and family history (37.23%, 35/94) compared with non-carriers (P = 3.62E-6 and 0.034, respectively). According to our data, we advanced the frequency of p.Ile1845fs variant and we confirmed that BRCA1: p.Ile1845fs variant was associated with increased risk of breast cancer (OR = 2.36, 95%CI = 1.26–4.89, P = 0.004).ConclusionsBRCA1: p.Ile1845fs variant was a frequently pathogenic mutation in breast cancer in Han Chinese women and our data may be helpful for diagnosis and therapy of breast cancer.

Comparison of Morphological and Genetic Characteristics of Avocados Grown in Tanzania

“…This implies a substantial amount of diversity harbored by the trees investigated and that the four genetic clusters were significantly distinct. The level of population differentiation (F ST ) observed in this study was higher than the values reported by Juma et al [ 25 ] for the same plant material when AMOVA was carried out on district-based populations (F ST = 0.061, p < 0.0001) and altitudinal groups (F ST = 0.025, p < 0.0001). Gross-German and Viruel [ 37 ] and Boza et al [ 4 ] found an overall population differentiation of 0.25 and 0.193, respectively, which are comparatively higher than the value obtained in our study.…”

“…Some genetic markers that have been applied are isozymes [ 16 ], minisatellites [ 17 ], variable number tandem repeats (VNTRs) [ 18 ], randomly amplified polymorphic DNA (RAPD) [ 19 ], and restriction fragment length polymorphisms (RFLP) [ 20 , 21 ]. Others are inter-simple sequence repeats (ISSR) [ 22 ], simple sequence repeat (SSR) [ 15 , 23 , 24 , 25 ], and single nucleotide polymorphisms (SNPs) [ 5 , 26 , 27 ]. Choosing which marker type to employ in a diversity study depends on the study objectives and available financial resources, expertise, and facilities [ 28 ].…”

“…Population genetics has been used in describing the genetic composition of avocado populations and mechanisms affecting the composition [ 15 , 23 , 24 , 25 ]. Bayesian cluster analysis employed in the STRUCTURE and discriminant analysis of principal components has been widely utilized in studying the population structure of crops, including avocado [ 5 , 24 , 25 , 26 , 29 ]. Bayesian cluster analysis generates genetic clusters (genetic populations) with individuals in each cluster having distinctive allele frequencies at the investigated loci [ 30 , 31 , 32 ].…”

“…Tanzania rises from the sea level to more than 2900 m above sea level. The country has varying topographies, soils, and climates, which support the growth of different cultivars of avocados [ 13 , 25 ]. Although avocado is grown in several regions of Tanzania for the export and domestic markets [ 33 ], only two studies have been executed to characterize this germplasm based on morphological traits [ 13 ] and SSR markers [ 25 ].…”

“…The country has varying topographies, soils, and climates, which support the growth of different cultivars of avocados [ 13 , 25 ]. Although avocado is grown in several regions of Tanzania for the export and domestic markets [ 33 ], only two studies have been executed to characterize this germplasm based on morphological traits [ 13 ] and SSR markers [ 25 ]. The present study aimed to compare morphological and genetic characteristics of this germplasm and uncover correlations existing among the morphological and genetic characteristics and the geographical sampling locations.…”