Genetic Profiling of GADD45A (1506T>C) Single Nucleotide Polymorphism rs3783469 in Breast Cancer Development

Abstract

Objective: To assess the association between the growth arrest and deoxyribonucleic acid damage 45 alpha (1506 thymine > cytosine) polymorphism (reference single nucleotide polymorphism cluster ID 3783469) and breast cancer development in Pakistani females. Method: The case-control study was conducted at Riphah International University, Islamabad, Pakistan, in collaboration with Pakistan Railway General Hospital, Rawalpindi, Pakistan, from November 22, 2023, to October 8, 2024, and comprised diagnosed cases of breast cancer in group 1 and healthy controls in group 2. Blood samples were collected, and allele-specific tetra amplification refractory mutation system polymerase chain reaction and gel electrophoresis were carried out to determine the association of respective genotypes and allele frequencies using specific primers. Data was analysed using SPSS 27. Results: Of the 340 women, 170(50%) with mean age 51.06±9.74 years (range: 30-76 years) were in group 1, and 170(50%) with mean age 56.84±11.5 years (range: 26-82 years) were in group 2.  The thymine-cytosine genotype was more frequent in group A compared to group B [110(64.7%) vs. 33(19.4%)], while the thymine-thymine genotype predominated in group B [137(80.6%) vs. 60(35.3%); p<0.0001]. The cytosine-cytosine genotype was absent in both the groups. Genotype distribution and allele frequencies were significantly associated with breast cancer risk (p<0.0001). The associations were significant regardless of age stratification p<0.05). Conclusion: The incidence of breast cancer development was found to be elevated among females carrying the thymine-cytosine genotype, whereas the thymine-thymine genotype played a protective role among the healthy subjects. Key Words: Breast cancer, GADD45A, Single nucleotide polymorphism.