Dissertation committee:
Δημήτριος Τραφαλής Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Χριστίνα Τεσσερομάτη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Χριστίνα Δάλλα Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Γκρινιάτσος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεωργία Βρυώνη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ιορδάνης Μουρούζης Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αθανάσιος Αρμακόλας Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Lung cancer incidence steadily decreased by 2.6% per year in men and 1.1% per year in women from 2006 to 2007, primarily due to differences in smoking cessation .
However, the number of new cancer cases in 2023 is still estimated at 238,340, with all new cancer diagnoses expected to increase by 12.2%.
Among all cancer cases, lung cancer remains the deadliest cancer in both women and men, with an estimated 127,070 deaths in 2023 (20.8% of all cancer deaths), followed by breast and prostate cancers. It is the third most common cancer overall.
Histologically, lung cancer is broadly classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC, which is further divided into squamous cell carcinoma and non-squamous cell carcinoma).
Ionizing radiation is still commonly used as part of the treatment of many malignancies, including lung cancer.
This is an essential part of treatment because it reduces the risk of local recurrence, increases survival rates, and often reduces many symptoms such as pain, obstruction, and bleeding.In this way, it can shrink tumors and destroy cells, making it useful in adjuvant or neoadjuvant settings.
Radiotherapy is a treatment of cancer patients using ionizing radiation, most commonly in the form of X-rays and gamma rays.
Radiation is usually emitted internally or externally. In external radiation therapy (EBRT), a linear accelerator produces the X-rays, while internal radiation therapy (brachytherapy) is primarily performed by a gamma ray source, such as a radioactive isotope, that is introduced into the patient's body. EBRT doses are typically administered in fractions due to the increased potential (4-20 mV) and associated damage to surrounding normal tissue, whereas internal radiation has less intense potentials (0.6-1 mV) and is more localized effect can be obtained, limiting normal tissue damage.
Radiation therapy has direct or indirect effects on all living cells. In particular, they can damage a cell's DNA, proteins, and lipids by directly disrupting the structure of atoms or indirectly by causing the production of reactive species. Therefore, atoms and molecules attacked by radiation release electrons and produce ions that form active oxygen and nitrogen species.
Water is a major source of reactive oxygen species (ROS) such as superoxide anion (O2·-), hydroxyl radical (HO·), and hydrogen peroxide (H2O2). Ionizing radiation also causes oxidative DNA damage (DNA breaks, base damage, sugar damage) and immunosuppression.
In one of these reactions, ONOO- interacts with guanine, thereby inducing nitrate damage such as 8-nitroguanine (8-NG). However, the glycosidic bond between 8-NG and deoxyribose is so unstable that it is spontaneously released from the DNA, creating an apurinic site. This apurinic site pairs with adenine during DNA synthesis. Therefore, a conversion from G: C to T: A takes place. After radiotherapy, in addition to the initial tissue damage, late tissue damage occurs due to the accumulation of ROS and RNS in the tissue over several months.
There appears to be a strong positive association between ionizing radiation and 8-NG levels in NSCLC patients. In particular, patients with squamous cell carcinoma appear to experience the greatest increase in this subgroup, which may have important prognostic implications. Biomarkers in cancer treatment are important to predict treatment failure or success and need to be individualized. Serum 8-NG levels may be a useful addition to lung cancer control. Further research is needed to confirm the results and delineate subpopulations with specific benefits.
The most common base damage caused by ROS is guanine. A hydroxyl group is added to the 8-position of the purine base to form 8-hydroxydeoxyguanosine (8-OHdG). 8-OhdG is the most studied oxidative DNA damage due to its pronounced mutagenic activity. To this end, this main form of free radical DNA damage is often measured as an indicator of the extent of DNA damage and oxidative stress, and is often measured by urinary excretion. ROS can be continuously detected in irradiated tissues and cells for weeks to months and can cause latent/delayed damage.
There appears to be a strong positive association between ionizing radiation and 8-OHdG levels in NSCLC patients.
In particular, patients with squamous cell carcinoma have the largest increase within this subgroup and may have the most prognostic significance. Biomarkers in cancer treatment are important to predict treatment failure or success and need to be individualized. Serum 8-OHdG levels may be a useful addition to lung cancer control.
Keywords:
Cancer, 8-OHdG, Radiotherapy, Biomarker, 8-NG
