Association of BRCA۱ Founder Mutations (۱۸۵delAG and ۵۳۸۲insC) and TNF-α -۳۰۸ Polymorphism with Familial Breast Cancer in Iranian Women

Background:Breast cancer is one of the leading causes of cancer-related mortality among women worldwide. Germline mutations in the *BRCA۱* gene and polymorphisms in the *TNF-α* gene have been implicated in breast cancer susceptibility. This study aimed to investigate the frequency of the *BRCA۱* ۱۸۵delAG and ۵۳۸۲insC mutations and their association with the *TNF-α* -۳۰۸ G>A polymorphism for the early diagnosis of breast cancer in Iranian women.Methods: A total of ۸۴ 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 *BRCA۱* ۱۸۵delAG and ۵۳۸۲insC mutations were analyzed by multiplex polymerase chain reaction (PCR), while the *TNF-α* -۳۰۸ 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 p۵۳, were evaluated using standard histopathological and immunohistochemical methods. Statistical analysis was performed using the chi-square test in Epi Info version ۷, with a significance level of *P* < ۰.۰۵.Results: Among the ۸۴ patients, ۳۸ had a positive family history of breast cancer and ۴۶ had no family history. In patients with a positive family history, three cases carried the *BRCA۱* ۵۳۸۲insC mutation and two carried the ۱۸۵delAG mutation, whereas only one ۵۳۸۲insC mutation was detected in patients without a family history. The distribution of *TNF-α* -۳۰۸ genotypes (AA, AG, and GG) was ۸, ۱۴, and ۱۶ cases, respectively, among patients with a family history, compared with ۲۵, ۱۲, and ۹ cases in those without a family history. Conclusion: The findings suggest that the *BRCA۱* ۱۸۵delAG and ۵۳۸۲insC mutations, together with the *TNF-α* -۳۰۸ 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.

کلیدواژه ها:

BRCA۱Breast cancer Familial breast cancerTNF-&alpha ، Founder mutation