GENETIC VULNERABILITY CAUSE PROPENSITY OF BREAST CANCER
Main Article Content
Keywords
breast cancer, ATM, CHEK2, BARD1, Genetic variants, Vulnerability, onset of cancer
Abstract
Breast cancer is a global disease affecting women of different ancestry, with Pakistan contributing to 15% of all cancer deaths. Risk factors include high energy intake, body lethargy, BMI, obesity, type II diabetes, dyslipidemia, high blood pressure, visceral obesity, and blood cholesterol imbalance. Genetic makeup plays a significant role, with mutations in genes like BRCA1, BRCA2, TP53, CHEK2, and RAD51C accounting for 20% of hereditary breast cancer in Pakistan. Moderate-risk genes, such as homozygous ataxia-telangiectasia (ATM), increase the risk of developing breast cancer. Around 20% of inherited breast cancer in Pakistan is caused by variations in high and moderate genetic risk genes. Therapeutic use for these mutations is yet to be established.
Methods: A case-control study at Jinnah Post Graduate Medical Center in Karachi, Pakistan, involved 200 participants aged 15-60 who had undergone medical and surgical intervention, chemotherapy, and radiotherapy. The study focused on ATM, CHEK2, and BARD1 gene variants on NCBI-Clinvar, focusing on hotpots, pathogenic variants, and those associated with breast cancers. Data was analyzed using SPSS, Excel, and chi square and Fisher exact tests for risk factors. The study found significant relationships with study characteristics using logistic and linear regression analysis.
Results: Breast cancer is a growing global disease influenced by genetic, environmental, personal, and lifestyle factors. Moderate-risk genes contribute to 10% of hereditary risk, with over 70% of patients having overexpressed estrogen receptors (ERs) leading to "ER-positive" tumors. Mutations in high and moderate susceptibility genes account for 20%-40% of lifetime breast cancer risk. Genetic testing and prophylactic bilateral mastectomy are effective risk reduction strategies. Mutations in BRCA1/2 gene involvement accelerate cancer growth, increasing ovarian, prostate, pancreatic, and breast cancer risks. A study focusing on triple negative patients and reference gene sequences of ATM, CHEK2, and BARD1 found that a panel of variants is needed for the population to detect cancer. This knowledge could lead to targeted therapies, tailored approaches to breast cancer treatment, and improved genetic counseling for individuals with mutations in these genes. Obesity is a significant factor in breast cancer cases, as found in Stacy Simon's 2022 study. Breast cancer risk is non-age-dependent, affecting all age groups. American-Indian women have the least risk at 7%, while white, black, Asian/Pacific Islander, and Hispanic women have similar risk.
Conclusion: Risk factors include high energy intake, body lethargy, high BMI, obesity, type II diabetes, high blood pressure, and blood cholesterol imbalance. Mutations in the ATM gene increase the risk of breast cancer, while mutations in the CHEK2 gene decrease it. Around 20% of hereditary breast cancer is accounted for by variants in high and moderate susceptibility genes. Understanding the correlation between these genes is crucial for refining risk assessment, enabling targeted genetic counseling, and advancing personalized cancer prevention and treatment.
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Dr. Kausar Abbas Saldera
Ph.D. Student, Associate Professor, Department of Physiology, BMSI, Jinnah Postgraduate Medical Centre, Karachi.
Dr. Syed Mehboob Alam
Professor, Department of Pharmacology, Jinnah Postgraduate Medical Center, Karachi.
Dr Ufaque Batool K. Samo
Mphil Scholar, Department of Physiology, BMSI, Jinnah Postgraduate Medical Centre, Karachi.
Dr Taseer Ahmed Khan
Professor, Department of Physiology, University of Karachi, Karachi.