Vahur Valvere

Statistical data demonstrate a concurrent rise in smoking prevalence and mental disorders, such as depression and anxiety, which may be attributed to contemporary lifestyle factors, including social media and recent global events. This indicates a potential correlation between these trends, as individuals with mental disorders may engage in smoking as a form of self-medication to alleviate anxiety. However, smoking is harmful and increases the risk of many diseases. Therefore, smoking cessation strategies are increasingly being considered. Nicotine is a naturally produced alkaloid in plants that makes smoking so addictive. Unfortunately, the public’s lack of understanding of the effects of nicotine leads to misleading claims in the public and media about its biological effects. Thus, current narrative literature review is focused on the examination of the biological effects of organic nicotine from various angles, considering the psychological aspects of addiction and the immune system. Analysis of recent data showed that nicotine not only causes addiction but also has therapeutic benefits in certain diseases (depression, anxiety, schizophrenia) and has anti-inflammatory properties (autoimmunity, neurodegenerative diseases), and a deeper understanding and a broader approach to its effects is needed.

This study aimed to characterize the ATP-synthesis by oxidative phosphorylation in colorectal cancer (CRC) and premalignant colon polyps in relation to molecular biomarkers KRAS and BRAF. This prospective study included 48 patients. Resected colorectal polyps and postoperative CRC tissue with adjacent normal tissue (control) were collected. Patients with polyps and CRC were divided into three molecular groups: KRAS mutated, BRAF mutated and KRAS/BRAF wild-type. Mitochondrial respiration in permeabilized tissue samples was observed using high resolution respirometry. ADP-activated respiration rate (V_max) and an apparent affinity of mitochondria to ADP, which is related to mitochondrial outer membrane (MOM) permeability, were determined. Clear differences were present between molecular groups. KRAS mutated CRC group had lower V_max values compared to wild-type; however, the V_max value was higher than in the control group, while MOM permeability did not change. This suggests that KRAS mutation status might be involved in acquiring oxidative phenotype. KRAS mutated polyps had higher V_max values and elevated MOM permeability as compared to the control. BRAF mutated CRC and polyps had reduced respiration and altered MOM permeability, indicating a glycolytic phenotype. To conclude, prognostic biomarkers KRAS and BRAF are likely related to the metabolic phenotype in CRC and polyps. Assessment of the tumor mitochondrial ATP synthesis could be a potential component of patient risk stratification.

In Estonia, women have much longer life expectancy than men. The aim of this study was to examine sex differences in cancer survival in Estonia and to explore the role of age at diagnosis, stage at diagnosis and tumour subsite. Using data from the population-based Estonian Cancer Registry, we examined the relative survival of adult patients diagnosed with nine common cancers in Estonia in 1995–2006 and followed up through 2011. Excess hazard ratios (EHR) of death associated with female gender adjusted for age, stage at diagnosis and tumour subsite were estimated. A total of 20 828 male and 13 166 female cases were analysed. The main data quality indicators were similar between men and women. Women had more cases with unknown extent of disease at diagnosis. Overall, the age-adjusted 5-year relative survival ratio was higher among women than men for all studied sites, but the difference was significant for cancers of mouth and pharynx (22% units), lung (5% units), skin melanoma (17% units) and kidney (8% units). The increase in survival over time was larger for women than men for cancers of mouth and pharynx, colon, rectum, kidney and skin melanoma. In multivariate analysis, women had a significantly lower EHR of death within five years after diagnosis for five of the nine cancers studied (cancers of mouth and pharynx, stomach, lung, skin melanoma and kidney). Adjustment for stage and subsite explained some, but not all of the women’s advantage. We found a significant female survival advantage in Estonia for cancers of mouth and pharynx, stomach, lung, kidney and skin melanoma. The differences in favour of women tended to increase over time as from the 1990s to the 2000s, survival improved more among women than among men. A large part of the women’s advantage is likely attributable to biological factors, but other factors, such as co-morbidities, treatment compliance or health behaviour, are also probable contributors to gender survival disparities in Estonia and merit further investigation. Our findings have implications for public health, early detection and cancer care in Estonia.

Changes in alternative splicing have been linked to cancer development. We hypothesized that changes occurring in tumor tissue can also be detected in the peripheral blood of cancer patients leading to discovery of blood biomarkers of breast cancer. Alternative splicing profiles of 94 genes were examined in cancerous breast tissue. Discriminating splice variants were analyzed in the peripheral blood of early stage (BCI/II) (stage I–II; n = 26), neoadjuvant receiving locally advanced breast cancer patients (LABC) (stage IIb–IIIa, b; n = 10) and healthy volunteers (n = 26) using qRT-PCR analysis. Changes in marker expression during neoadjuvant therapy were analyzed at 15 timepoints. High expression of REST-N50, the alternatively spliced variant of REST, was detected in the blood of LABC patients but not in BCI/II and healthy controls (p = 0.0032 and p = 0.0029, respectively). Expression levels of DOPEY1v2, the alternative splice variant of DOPEY1, in the blood could differentiate cancer from healthy controls (p = 0.024) and discriminate between patient groups (BCI/II vs LABC, p = 0.002). Positive response to neoadjuvant therapy of REST-N50-positive LABC patients correlated with a decrease in REST-N50 levels (p < 0.0001). Assessment of REST-N50 and DOPEY1v2 may prove useful in diagnostic blood tests of breast cancer. REST-N50 shows a high potential as a blood biomarker for evaluating the effectiveness of therapy in the neoadjuvant setting.

Survival from breast cancer remains lower in Estonia than in most other European countries. More advanced stage and larger tumors that have impact on survival may be a result of delay in seeking help for breast cancer symptoms. The aim of this study was to identify determinants of delayed presentation among breast cancer patients in Estonia.