Association of BRCA1 Founder Mutations (185delAG and 5382insC) and TNF-α -308 Polymorphism with Familial Breast Cancer in Iranian Women

Bagheri, Zahra; Sanjarian, Sara; Houshmand, Masoud; Rassi, Hossein

doi:10.22034/ppmj.2026.738545

Association of BRCA1 Founder Mutations (185delAG and 5382insC) and TNF-α -308 Polymorphism with Familial Breast Cancer in Iranian Women

Authors

Zahra Bagheri ¹

Sara Sanjarian ²

Masoud Houshmand ³

Hossein Rassi ¹

¹ Department of Biology, Islamic Azad University of Karaj.

² Department of Human Genetics, Iranian Academic Center for Education, Culture and Reseaech(ACECR)-Fars Branch Institute for Human Genetics Research.

³ Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

10.22034/ppmj.2026.738545

Abstract

Background:Breast cancer is one of the leading causes of cancer-related mortality among women worldwide. Germline mutations in the *BRCA1* gene and polymorphisms in the *TNF-α* gene have been implicated in breast cancer susceptibility. This study aimed to investigate the frequency of the *BRCA1* 185delAG and 5382insC mutations and their association with the *TNF-α* -308 G>A polymorphism for the early diagnosis of breast cancer in Iranian women.
Methods: A total of 84 archival breast tissue samples were collected from breast cancer patients treated at Khatam and Imam Khomeini hospitals. Genomic DNA was extracted using standard protocols. The *BRCA1* 185delAG and 5382insC mutations were analyzed by multiplex polymerase chain reaction (PCR), while the *TNF-α* -308 G>A polymorphism was determined using amplification refractory mutation system PCR (ARMS-PCR). Histopathological characteristics, including mitotic activity, necrosis, cellular pleomorphism, tumor grade, and the expression of ER, PR, and p53, were evaluated using standard histopathological and immunohistochemical methods. Statistical analysis was performed using the chi-square test in Epi Info version 7, with a significance level of *P* < 0.05.
Results: Among the 84 patients, 38 had a positive family history of breast cancer and 46 had no family history. In patients with a positive family history, three cases carried the *BRCA1* 5382insC mutation and two carried the 185delAG mutation, whereas only one 5382insC mutation was detected in patients without a family history. The distribution of *TNF-α* -308 genotypes (AA, AG, and GG) was 8, 14, and 16 cases, respectively, among patients with a family history, compared with 25, 12, and 9 cases in those without a family history. Conclusion: The findings suggest that the *BRCA1* 185delAG and 5382insC mutations, together with the *TNF-α* -308 GG genotype and clinicopathological characteristics, may serve as useful molecular markers for identifying women at increased risk of breast cancer. Their combined assessment may improve the early diagnosis and facilitate timely therapeutic intervention in Iranian women.

Keywords

BRCA1Breast cancer Familial breast cancerTNF-&alpha

Founder mutation

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