Lack of Association of BRCA1 and BRCA2 Variants with Breast Cancer in an Ethnic Population of Saudi Arabia, an Emerging High-Risk Area

Abstract

Incidence of breast cancer shows geographical variation, even within areas of ethnic homogeneity. Saudi Arabia has witnessed an increase in occurrence of breast cancer in its unexplored ethnic populations over the past few years. We aimed at determining whether any association exists between single nucleotide polymorphisms in breast cancer associated gene 1 (BRCA1) and breast cancer associated gene 2 (BRCA2) and the risk of breast cancer. TaqMan based Real Time Polymerase chain reaction genotyping assays were used to determine the frequency of single nucleotide polymorphisms in BRCA1 (rs799917) and BRCA2 (rs144848) in a group of 100 breast cancer patients and unaffected age matched controls of Saudi Arabian origin. The present data revealed that neither BRCA1 nor the BRCA2 studied variant show any significant association with the disease. This study failed to find any role of the concerned variants in breast cancer either as risk or as prognostic factors. The small number of patients registered was one of the limitations of this study. In summary, comparison of mutation profile with other ethnic populations and regions reflected both differences and similarities indicating co-exposure to a unique set of risk factors. The differences could be due to exposure to particular environmental carcinogens; different lifestyle, reproductive pattern; dietary or cultural practices of Saudi Arabian women that need further investigations.

Association between BRCA1 rs799917 polymorphism and breast cancer risk: A meta-analysis of 19,878 subjects

“…And detailed characteristics of these studies were presented in Table 1. The distribution of genotypes in the controls was in agreement with HWE for all except for one study (P = 0.005) [22], and omission of this individual study did not change the result substantially (data not shown).…”

“…1). Finally, a total of 8 case-control articles met our inclusion criteria [15][16][17][18][19][20][21][22], including 19,878 subjects. And detailed characteristics of these studies were presented in Table 1.…”

Identification and frequency of the rs12516 and rs8176318 BRCA1 gene polymorphisms among different populations

“…In addition, it was demonstrated that the BRCA1 polymorphism, rs799917, was associated with breast cancer risk (18). By contrast, Hasan et al (19) reported that rs799917 demonstrated no significant association with breast cancer in 100 patients with breast cancer in Saudi Arabia (19). Therefore, the role of genetic variants in the BRCA1 3'UTR and its post-transcriptional regulation remains unclear.…”

“…Therefore, the role of genetic variants in the BRCA1 3'UTR and its post-transcriptional regulation remains unclear. Such differences may be due to reproductive patterns, in addition to exposure to particular environmental carcinogens, different lifestyles and different genetic backgrounds (19). The present study focused on the polymorphisms in the BRCA1 3'UTR, and identified that rs12516 and rs8176318 had potential miRNA binding sites.…”

No Association between BRCA1 Immunohistochemical Expression and Tumor Grade, Stage or Overall Survival in Platinum-Treated Epithelial Ovarian Cancer Patients

“…Our results were intermediate between Sirisabya et al (2007), who found no correlation between the BRCA1 expression and any of the clinicopathological variables, and Werness et al (2004), who detected fewer grade 1 and stage I cancers in BRCA1 positive patients than in BRCA1 negative patients. Similarly, polymorphisms of breast cancer susceptibility gene BRCA1 had no statistically significant correlation with clinicopathological characteristics of breast cancer in Saudi population (Hasan et al, 2013). In addition, Lan et al (2013) observed no significant differences in the methylation frequencies of BRCA1 between stages and ages of ovarian cancer patients.…”