## 1 Introduction
For instance, o-quinone metabolism indirectly generates free hydroxyl radicals, the most harmful oxidizing agents. These molecules induce DNA damage via multiple mechanisms, such as inducing single-strand breaks, chromosomal aberrations and 8-oxo-2\({}^{\prime}\)-deoxyguanosine formation. The quinones and semiquinones can also inflict direct cellular DNA damage by forming adducts, culminating in genotoxic effects (depurination). Studies have highlighted the capability of catechol estrogens, o-quinones or their metabolites to bind to ERs and, on further transportation to the ERE in the nucleus, to result in DNA mutation via free radical emission [24; 25]. A prospect of further caution pertains to overexpressed CYP1B1 whichis enacted through long-lasting tobacco combustion. Thereby, the risk of concurrent free radical and ROS-induced damage is higher in chain smokers or those with a long smoking association. Estrogens have important roles in lung carcinogenesis and subsequent complications of lung cancers [26; 27; 28]. Of note, NSCLC accounts for about \(\sim\)85% of all lung cancers [29] with an abysmal (13-18%) five-year survival rate [30; 31]. Contrary to male gonads (testes), female gonads (ovaries) produce higher levels of aromatase, consequently having higher estrogen amounts in the blood [32]. Thus, females have a greater risk of being affected by various estrogen-dependent complications, including cancers [33; 34]. Studies reveal a more than twice higher adenocarcinoma risk in smoking females advised or undergoing estrogen replacement therapy (ERT) than those not subjected to ERT, odds proportion being 32.4 to 13.1. Contrary to this, non-smoking women taking ERT exhibited no significant adenocarcinoma \begin{table}
\begin{tabular}{c c} \hline \hline
**Type of Estrogen** & **Sources** \\ \hline Natural (Endogenous) & Extensively by gonadal organs (ovary/tests), low-level production in various organs due to aromatase generation (e.g., lungs, brain, etc.) \\ \hline Synthetic (Exogenous) & \\ (Ethinyl estradiol, diethylstilbestrol, estradiol & Either as constituent of contraceptive pills or hormone response therapy \\ \hline Phytoestrogen (Exogenous) & Plant foods such as soy beans, tofu, tempeh, soy beverages, linseed (flax), sesame seeds, wheat (as lignans), berries (resveratrol), oats, barley, dried beans, lentils, rice, mung beans, apples, carrots, wheat germ, ricebran, soy linseed bread. \\ \hline Xenoestrogen (Exogenous) & Plastics (water bottles, disposable cups, plastic wrap, food containers), pesticides (used on non-organic fruits and vegetables), tap water (chlorine and runoff byproducts), chemicals in cosme, lotions, shampoos and other body care materials \\ \hline \hline \end{tabular}
\end{table} 
Table 1: The different sources of estrogens, distinguished via endogenous and exogenous origins. Figure 1: The different availability routes of estrogen in human body, distinguished into endogenous (within the body) and exogenous (outside the body). While exogenous sources present a greater diversity, endogenous estrogen is enabled through 17-ß-estradiol (E2) and its metabolites. risk [35]. Lately, though, the impact of HRT on a possible lung cancer manifestation has revealed a 50% higher risk for women under a combined hormone therapy (estrogen with progestin) [36; 37; 38; 39]. Besides increased lung cancer risk, the HRT mediated via estradiol and progesterone combined also exhibited a significant association between a younger median age for lung cancer diagnosis and shorter median survival duration [39; 40; 41]. Apart from CYP1B1, the CYP1A1 gene encodes for phase I enzyme which metabolizes polycyclic aromatic hydrocarbons (PAHs) in tobacco smokes, preventing the precarcinogen from turning carcinogenic [42]. The circulating steroid hormones in females impair this CYP1A1 action due to their interaction with receptors in the lungs of sufferers. As a result, the carcinogen formation becomes unregulated which aggravates the LC risk.