Investigating Family History Status, Frequency of BRCA1/BRCA2 Mutations and Molecular Subtypes of Breast Cancer in the Highly Consanguineous Eastern Saudi Arabia Population: Implications in the Post-COVID-19 Era

ORIGINAL ARTICLE
Tahani Al-Qurashi, Sarah Balghonaim, Kanza Rashid, Haya Albunyan, Hattan Alduhailan, Latiffah Almqhawi, Irtaza Fatima Zafar, Rehab Abubaker, Anees R Malik, Hani Mustafa, Yaqob Samir Taleb, Tariq Karar, et al.

 
For citation: Al-Qurashi T, Balghonaim S, Rashid K, Albunyan H, Alduhailan H, Almqhawi L, Zafar IF, Abubaker R, Malik AR, Mustafa H, Taleb YS, Karar T, Alanazi N, Al-Garni A, Al-Mukhaylid S, Iqbal Z. Investigating Family History Status, Frequency of BRCA1/BRCA2 Mutations and Molecular Subtypes of Breast Cancer in the Highly Consanguineous Eastern Saudi Arabia Population: Implications in the Post-COVID-19 Era. International Journal of Biomedicine. 2025;15(2):309-318. doi:10.21103/Article15(2)_OA7
 
Originally published June 5, 2025
 

Abstract: 

Background: This study aimed to determine the incidence of FBC, its association with clinical and demographic factors, and autosomal dominant BRCA1/BRCA2 mutations in BC patients in Al-Ahsa, Eastern Saudi Arabia. Given the high frequency of consanguineous marriages in this less urbanized area, we hypothesized an increase in family history and involvement of recessive genes, but lower frequencies of BRCA1/BRCA2 mutations in BC genes.
Methods and Results: The study included 115 patients diagnosed with BC at King Abdulaziz Hospital, Al-Ahsa, between 2007 and 2022. BRCA1/BRCA2 gene mutations were analyzed using previously established protocols. The incidence of BC increased from 2009 to 2017, peaking in 2012, with 98.3% of cases in females and 53.1% diagnosed above age 50. Also, 36% of patients had FBC, with one or more affected family members having a family history of BC/OC. Both BRCA1/BRCA2 mutations were found in 12.2% of FBC but absent in non-FBC, with BRCA2 mutations being more prevalent (80%) than BRCA1. Luminal-A/B was the most common subtype; bone and liver were the most frequent metastasis sites. Luminal-A molecular type was significantly correlated with unilateral BC in non-FBC patients than in FBC. TNM stage II was most common (49%), with FBC more likely to be diagnosed at earlier TNM stages than non-FBC. A strong correlation was found between BC unilaterality and bone metastasis in FBC patients.
Conclusion: Our findings show a higher rate of FBC in Eastern Saudi Arabia, with strong associations to unilaterality and bone metastases. The prevalence of favorable molecular subtypes, early TNM stages, lower BRCA1/BRCA2 mutations, and potentially high recessive genetic influence indicate the need for mandatory OMICS-based genetic testing for those patients under 65 in this region.   

Keywords: 
breast cancer • familial predisposition • genetic testing • triple-negative breast cancer
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Received April 7, 2025.
Accepted May 30, 2025.
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