Body Weight, Physical Activity, and Risk of Cancer in Lynch Syndrome

Lynch syndrome (LS) increases cancer risk. There is considerable individual variation in LS cancer occurrence, which may be moderated by lifestyle factors, such as body weight and physical activity (PA). The potential associations of lifestyle and cancer risk in LS are understudied. We conducted a retrospective study with cancer register data to investigate associations between body weight, PA, and cancer risk among Finnish LS carriers. The participants (n = 465, 54% women) self-reported their adulthood body weight and PA at 10-year intervals. Overall cancer risk and colorectal cancer (CRC) risk was analyzed separately for men and women with respect to longitudinal and near-term changes in body weight and PA using extended Cox regression models. The longitudinal weight change was associated with an increased risk of all cancers (HR 1.02, 95% CI 1.00–1.04) and CRC (HR 1.03, 1.01–1.05) in men. The near-term weight change was associated with a lower CRC risk in women (HR 0.96, 0.92–0.99). Furthermore, 77.6% of the participants retained their PA category over time. Men in the high-activity group had a reduced longitudinal cancer risk of 63% (HR 0.37, 0.15–0.98) compared to men in the low-activity group. PA in adulthood was not associated with cancer risk among women. These results emphasize the role of weight maintenance and high-intensity PA throughout the lifespan in cancer prevention, particularly in men with LS

Body Weight, Physical Activity, and Risk of Cancer in Lynch Syndrome

Lynch syndrome (LS) increases cancer risk. There is considerable individual variation in LS cancer occurrence, which may be moderated by lifestyle factors, such as body weight and physical activity (PA). The potential associations of lifestyle and cancer risk in LS are understudied. We conducted a retrospective study with cancer register data to investigate associations between body weight, PA, and cancer risk among Finnish LS carriers. The participants (n = 465, 54% women) self-reported their adulthood body weight and PA at 10-year intervals. Overall cancer risk and colorectal cancer (CRC) risk was analyzed separately for men and women with respect to longitudinal and near-term changes in body weight and PA using extended Cox regression models. The longitudinal weight change was associated with an increased risk of all cancers (HR 1.02, 95% CI 1.00–1.04) and CRC (HR 1.03, 1.01–1.05) in men. The near-term weight change was associated with a lower CRC risk in women (HR 0.96, 0.92–0.99). Furthermore, 77.6% of the participants retained their PA category over time. Men in the high-activity group had a reduced longitudinal cancer risk of 63% (HR 0.37, 0.15–0.98) compared to men in the low-activity group. PA in adulthood was not associated with cancer risk among women. These results emphasize the role of weight maintenance and high-intensity PA throughout the lifespan in cancer prevention, particularly in men with LS

Menopausal transition alters female skeletal muscle transcriptome

Objectives Although skeletal muscle is a target of hormonal regulation, the muscle transcriptome, including messenger-RNA (mRNA), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) has not previously been studied across the menopausal transition. Thus, we took a multi-RNA-omics approach to get insight into transcriptome-wide events of menopause. Methods We included baseline and follow-up muscle samples from seven early (EarlyMT) and 17 late perimenopausal (LateMT) women transitioning to early postmenopause during the study. Total RNA was sequenced and differential expression (DE) of the transcriptome was investigated. Gene functions were investigated with pathway analyses and protein level expression with Western Blot. Results We found 30 DE mRNA genes in EarlyMT and 19 in LateMT participating in pathways controlling cell death, growth, and interactions with the external environment. Lack of protein level changes may indicate a specific role of the regulatory RNAs during menopause. 10 DE lncRNA transcripts but no DE lncRNA genes were identified. No DE miRNAs were found. We identified putative regulatory networks likely to be affected by estradiol availability. Changes in gene expression were correlated with changes in body composition variables, indicating that muscularity and adiposity regulators are affected by menopausal transition. We also found correlations between gene expression and physical activity levels. Conclusions The observed DE genes and their regulatory networks offer novel mechanistic insights into factors affecting body composition during and after menopause. Our results imply that physiological deteriorations orchestrated by the muscle transcriptome likely depend on the magnitude of hormonal change and are influenced by physical activity

The potential role of circulating-micro-RNA-21, -146a, -221 and -222 as non-invasive biomarkers in acute exercise training

Elimistössä kiertävät mikro-RNAt (ci-miRNAt) säätelevät geenien toimintaa ja toimivat viestimolekyyleinä kudosten välillä. Tämän vuoksi niitä on mahdollista hyödyntää merkkimolekyyleinä mm. tutkittaessa liikunnan aiheuttamia vasteita kehossa. Hyvä merkkimolekyyli on helposti kerättävissä ilman invasiivisia menetelmiä. Hien on uskottu olevan sopiva tähän käyttötarkoitukseen. Tässä tutkielmassa tutkittiin, että voidaanko hiestä löytää ci-miRNA:ta ja korreloivatko mahdolliset löydökset myös veren seerumin kanssa. Tutkimuksessa havaittiin ci-miRNA:ta löytyvän hiestä ja ci-miRNA-146a pitoisuuden nousseen hiessä VO2 max testin jälkeen, mutta veressä ei havaittu mitään vasteita. Myös korrelaatiot veren ja hien välillä olivat erittäin heikot. Tämän vuoksi ci-miRNA:ja ei voida pitää luotettavina merkkimolekyyleinä VO2 max testille eikä hienkeruuta voida suositella merkkimolekyylien keräämiseen toistaiseksi. ci-miRNA:ja voidaan kuitenkin yhä pitää potentiaalisia merkkimolekyyleinä liikunnalle. Lisätutkimusta ci-miRNA:en toiminnasta ja tutkimismenetelmistä vaaditaan vielä runsaasti.The potential use of circulating micro-RNAs (ci-miRNAs) as non-invasive biomarkers to monitor exercise adaptation has raised interest recently. Sweat is held as suitable candidate for such non-invasive biomarker harvest as it is easily collected without invasive methods. Thus, the aims of the study were to investigate if ci-miRNAs can be detected from sweat and to further examine circulating profiles of the same ci-miRNAs as acute response to VO2 max test in sweat and serum. Also, it was examined whether the ci-miRNA profiles correlated between the body fluids. It was observed, for the first time, that sweat contained ci-miRNAs and the expression of ci-miRNA-146a was upregulated after acute exercise. However, the ci-miRNA correlations between the body fluids were weak. Based on our observations, sweat harvesting cannot be supported after VO2 max test and ci-miRNAs cannot be utilized as VO2 max biomarkers currently, but they hold potential to function as such in the future. Until then, several obstacles regarding to exercise study designs and miRNA overall methodology should be overcome

Paikkatietojen käyttö aluerakenteen muutoksen seurannassa

Tässä tutkimuksessa on selvitetty aluerakenteen ilmenemistä ja perusteltu aluerakenteen muutoksen seurannan tärkeyttä. Ajantasaisella aluerakennekuvalla on merkitystä toimintojen suunnittelussa, ohjaamisessa ja päätöksenteossa. Aluerakenteen "terveydellä" on myös kosketuspintansa kestävän kehityksen periaatteeseen. Koska aluerakenteen muutos on ilmiönä laaja-alainen ja seurausta yhteiskunnassa tapahtuneista ja käynnissäolevista muutosprosessista, on sen seurannan myös oltava laajaan tietopohjaan perustuvaa. Suomessa tiedonkeruu ja tietohuolto ovat jo pitkään olleet aivan kansainvälistä kärkitasoa ja tarjoavat näin oivalliset puitteet ilmiöiden ajalliseen seurantaan. Vasta nykyiset paikkatietotekniikat todella mahdollistavat tietoaineistojen täysipainoisen hyödyntämisen. Paikkatietoja voidaan pitää luonnollisimpina ja parhaiten aluerakenteen ilmiötä valaisevina tietolähteinä ja siten spatiaalisten analyysien ja kartallisen ilmaisutavan olevan soveliaimpia kyseessä olevan ongelmakentän ratkaisussa. Paikkatietoja käsittelevässä tutkimuksen osassa selvitetään ensin paikkatiedon tärkeimpiä käsitteitä ja paikkatietojärjestelmiä. Myös paikkatietojen laadun osatekijät esitellään. Paikkatietojen saatavuus (tekijänoikeudet, hinnoittelu ja tietosuoja) on vielä tänä päivänä ongelmallista. Paikkatietoanalyysit ovat keino käsitellä lähtöaineistoa halutun tiedon esille saamiseksi. Analyysit voivat perustua puhtaasti visuaaliseen tarkasteluun, ne voivat sisältää yksinkertaista geometrista laskentaa tai ne voivat olla matemaattisia malleja. Paikkatietojen visuaalisuus on olennainen osa niiden hyödyllisyyttä. Tämän tutkimustyön toisena tarkoituksena on kartoittaa olemassa olevat järjestelmät ja menetelmät, jotka soveltuisivat aluerakenteen seurantaan ja soveltavat nykyaikaisia paikkatietotekniikan keinoja. Menetelmät on jaettu kahteen pääluokkaan; perinteisiin ja toisaalta paikkatietotekniikoita hyödyntäviin menetelmiin. Lopuksi tuodaan esille aluerakenteen muutoksen seurannan kehitystarpeita ja hahmotellaan Suomen Kuntaliitolle suuntaviivoja oman aluerakenteen muutoksen seurannan järjestämiseksi. Suomen Kuntaliiton on kuntien edunvalvojana oltava tietoinen aluerakenteen tilasta ja pystyttävä reagoimaan siinä tapahtuviin muutoksiin

Systemic circulating microRNA landscape in Lynch syndrome

Circulating microRNAs (c-miRs) are small non-coding RNA molecules that migrate throughout the body and regulate gene expression. Global c-miR expression patterns (c-miRnomes) change with sporadic carcinogenesis and have predictive potential in early detection of cancers. However, there are no studies that have assessed whether c-miRnomes display similar potential in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), known as Lynch syndrome (LS), who are predisposed to highly increased cancer risk. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers, sporadic rectal cancer patients and non-LS controls. We showed for the first time that cancer-free path_MMR carriers have a systemic c-miRnome of 40 differentially expressed c-miRs that can distinguish them from non-LS controls. The systemic c-miRnome of cancer-free path_MMR carriers also resembles the systemic c-miRnomes of cancer patients with or without path_MMR. Our pathway analysis linked the found differentially expressed c-miRs to carcinogenesis. A total of 508 putative target genes were identified for 32 out of 40 differentially expressed c-miRs, and 238 of them were enriched in cancer-related pathways. The most enriched c-miR-target genes include well-known oncogenes and tumor suppressor genes such as BCL2, AKT3, PIK3CA, KRAS, NRAS, CDKN1A and PIK3R1. Taken together, our findings suggest that LS and sporadic carcinogenesis share common biological pathways and alterations in these pathways can produce a c-miR signature which can track potential oncogenic stress in cancer-free path_MMR carriers. Therefore, c-miRs hold potential in monitoring the LS risk stratification patterns during clinical surveillance or cancer management.peerReviewe

Extracellular vesicles and high‐density lipoproteins : Exercise and oestrogen‐responsive small RNA carriers

Decreased systemic oestrogen levels (i.e., menopause) affect metabolic health. However, the detailed mechanisms underlying this process remain unclear. Both oestrogens and exercise have been shown to improve metabolic health, which may be partly mediated by circulating microRNA (c-miR) signalling. In recent years, extracellular vesicles (EV) have increased interest in the field of tissue crosstalk. However, in many studies on EV-carried miRs, the co-isolation of high-density lipoprotein (HDL) particles with EVs has not been considered, potentially affecting the results. Here, we demonstrate that EV and HDL particles have distinct small RNA (sRNA) content, including both host and nonhost sRNAs. Exercise caused an acute increase in relative miR abundancy in EVs, whereas in HDL particles, it caused an increase in transfer RNA-derived sRNA. Furthermore, we demonstrate that oestrogen-based hormonal therapy (HT) allows the acute exercise-induced miR-response to occur in both EV and HDL particles in postmenopausal women, while the response was absent in nonusers.peerReviewe

MicroRNAs in extracellular vesicles in sweat change in response to endurance exercise

Abstract Background: To date, microRNAs (miRs) carried in extracellular vesicles (EVs) in response to exercise have been studied in blood but not in non-invasively collectable body fluids. In the present study, we examined whether six exercise–responsive miRs, miRs-21, -26, -126, -146, -221, and -222, respond to acute endurance exercise stimuli of different intensities in sweat. Methods: We investigated the response of miRs isolated from sweat and serum EVs to three endurance exercise protocols: (1) maximal aerobic capacity (VO2max), (2) anaerobic threshold (AnaT), and (3) aerobic threshold (AerT) tests. Sauna bathing was used as a control test to induce sweating through increased body temperature in the absence of exercise. All protocols were performed by the same subjects (n = 8, three males and five females). The occurrence of different miR carriers in sweat and serum was investigated via EV markers (CD9, CD63, and TSG101), an miR-carrier protein (AGO2), and an HDL-particle marker (APOA1) with Western blot. Correlations between miRs in sweat and serum (post-sample) were examined. Results: Of the studied miR carrier markers, sweat EV fractions expressed CD63 and, very weakly, APOA1, while the serum EV fraction expressed all the studied markers. In sweat EVs, miR-21 level increased after AerT and miR-26 after all the endurance exercise tests compared with the Sauna (p < 0.050). miR-146 after AnaT correlated to sweat and serum EV samples (r = 0.881, p = 0.004). Conclusion: Our preliminary study is the first to show that, in addition to serum, sweat EVs carry miRs. Interestingly, we observed that miRs-21 and -26 in sweat EVs respond to endurance exercise of different intensities. Our data further confirmed that miR responses to endurance exercise in sweat and serum were triggered by exercise and not by increased body temperature. Our results highlight that sweat possesses a unique miR carrier content that should be taken into account when planning analyses from sweat as a substitute for serum