Genetic Predisposition of PON1 L55M (T172A) and Oxidative Stress in Breast Carcinogenesis among Pakistani Population
Genetic Predisposition of PON1 L55M (T172A) and Oxidative Stress in Breast Carcinogenesis among Pakistani Population
Syeda Abiha Zehra Jaffari1, Tuba Abid1, Muhammad Zohaib2, Ghulam Haider3 and Zehra Hashim1*
ABSTRACT
Breast cancer has become a global health issue across the world including Pakistan. In 2020, an estimated five-year prevalence of breast cancer is 30.1% depicting the major cause of socio-economic burden in our country. Owing to the fact that oxidative stress plays a crucial role in breast cancer progression, this study aimed to inspect the role of exonic region variant PON1 L55M and the effect of PON1 enzyme activity in accelerating the disease among Pakistani females. In this population-based case-control study n=222 females were included. PON1 L55M (T172A) genetic variation was determined by means of tetra-ARMS PCR. PON1 paraoxonase and arylesterase enzyme activities and levels of lipid peroxidation marker were assessed to figure out the level of oxidative stress. The odds ratio was calculated using MedCalc® software and gene counting. SPSS® 16.0 was used to perform Chi-square test, independent t-test and Pearson correlation. In our results, we found that genetic variant PON1 55M (172A) was significantly (p<0.001) correlated with an increased risk of breast cancer. PON1 activities were found to be decreased (p<0.001) with increased MDA levels (p<0.001) in the diseased group. Pearson correlation indicated an inverse correlation (r = - 0.1215, p<0.01) between PON1 enzyme activity and MDA levels. In breast cancer patients with 55M allele, activity of PON1 was found to be decreased (p<0.001). It is concluded that increased levels of MDA with a concomitant decrease in PON1 activity could be responsible for disease acceleration via increased oxidative burden. Reduced PON1 activity in breast cancer patients with PON1 L55M variant might be a contributing factor to the disease progression.
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