Interaction of sedentary behaviour and educational level in breast cancer risk

Objective This cross-sectional study aims to analyse the relationship between sedentary behaviour and breast cancer (BC) risk from a social perspective. Methods Women aged 45–70 who participated in the Valencia Region Breast Cancer Screening Programme (2018–2019) were included, with a total of 121,359 women analysed, including 506 with cancer and 120,853 without cancer. The response variable was BC (screen-detected) and the main explanatory variable was sedentary behaviour (≤2 / >2-≤3 / >3-≤5 / >5 hours/day, h/d). Nested logistic regression models (M) were estimated: M1: sedentary behaviour adjusted for age and family history of BC; M2: M1 + hormonal/reproductive variables (menopausal status, number of pregnancies, hormone replacement therapy; in addition, months of breastfeeding was added for a subsample of women with one or more live births); M3: M2 + lifestyle variables (body mass index, smoking habits); M4: M3 + socioeconomic variables (educational level, occupation); Final model: M4 + gender variables (childcare responsibilities, family size). Interaction between sedentary behaviour and educational level was analysed in the Final model. Moreover, for the whole sample, postmenopausal women and HR+ BC, the Final model was stratified by educational level. Results Sedentary behaviour was associated with an increased risk of BC with a nearly statistically significant effect in the Final model (>2-≤3 h/d: OR = 1.22 (0.93–1.61); >3-≤5 h/d: OR = 1.14 (0.86–1.52); >5: OR = 1.19 (0.89–1.60)). For women with a low educational level, sitting more than 2 h/d was associated with an increased risk of BC in the whole sample (>2-≤3 h/d OR = 1.93 (1.19–3.21); in postmenopausal women (>2-≤3 h/d, OR = 2.12 (1.18–2.96), >5h/d OR = 1.75 (1.01–3.11)) and in HR+ BC (>2-≤3h/d, OR = 2.15 (1.22–3.99)). Similar results were observed for women with one or more live births. Conclusions Sitting >2 h/d is associated with BC risk in women with low educational level, especially in postmenopausal women and those with live births.M.P-C: This work was supported by the Generalitat Valenciana and the European Social Fund [grant number ACIF/2019/085]

Construction of an individual socioeconomic status index for analysing inequalities in colorectal cancer screening

Objective: To construct an individual socioeconomic status index (ISESI) with information available in the Population Information System of the Region of Valencia, Spain, and use it to analyse inequalities in a colorectal cancer screening programme (CRCSP). Methods: Cross-sectional study of men and women aged between 50 and 75 at the time of the study (2020) that were selected from the target population of the Region of Valencia CRCSP. (study sample 1,150,684). First, a multiple correspondence analysis was performed to aggregate information from the Population Information System of the Region of Valencia into an ISESI. Second, data from the 2016 Region of Valencia Health Survey were used for validation, and finally the relationship between CRCSP participation and the ISESI was analysed by logistic regression models. Results: The variables included in the index were nationality, employment status, disability, healthcare coverage, risk of vulnerability and family size. The most important categories for determining the highest socioeconomic status were being employed and not being at risk of social vulnerability, and being unemployed and at risk of social vulnerability for determining the lowest socioeconomic status. Index validation demonstrated internal and external coherence for measuring socioeconomic status. The relationship between CRCSP participation and the ISESI categorised by quartile (Q) showed that Q4 (the lowest socioeconomic status) was less likely to participate OR = 0.769 (0.757–0.782) than Q1 (the highest socioeconomic status), and the opposite was found for Q2 OR = 1.368 (1.347–1.390) and Q3 OR = 1.156 (1.137–1.175). Conclusions: An ISESI was constructed and validated using Population Information System data and made it possible to evaluate inequalities in colorectal cancer screening.AMB, DS: PI18/01669, the Instituto de Salud Carlos III, co-founded by the European Regional Development Fund (ERDF). https://www.isciii.es

Factors influencing participation in colorectal cancer screening programs in Spain

To analyze the sociodemographic and organizational factors influencing participation in population-based colorectal cancer screening programs (CRCSP) in Spain, a retrospective study was conducted in a cohort of people invited to participate in the first 3 screening rounds of 6 CRCSP from 2000 to 2012. Mixed logistic regression models were used to analyze the relationship between sociodemographic and organizational factors, such as the type of fecal occult blood test (FOBT) used and the FOBT delivery type. The analysis was performed separately in groups (Initial screening-first invitation, Subsequent invitation for previous never-responders, Subsequent invitation-regular, Subsequent invitation-irregular intervals). The results showed that, in the Initial screening-first invitation group, participation was higher in women than in men in all age groups (OR 1.05 in persons aged 50–59 years and OR 1.12 in those aged 60–69 years). Participation was also higher when no action was required to receive the FOBT kit, independently of the type of screening (Initial screening-first invitation [OR 2.24], Subsequent invitation for previous never-responders [OR 2.14], Subsequent invitation-regular [OR 2.03], Subsequent invitation-irregular intervals [OR 9.38]) and when quantitative rather than qualitative immunological FOBT (FIT) was offered (Initial screening-first invitation [OR 0.70], Subsequent invitation for previous never-responders [OR 0.12], Subsequent invitation-regular [OR 0.20]) or guaiac testing (Initial screening-first invitation [OR 0.81], Subsequent invitation for previous never-responders [OR 0.88], Subsequent invitation-regular [OR 0.73]). In conclusion, the results of this study show that screening participation could be enhanced by inclusion of the FOBT kit with the screening invitation and the use of the quantitative FIT.This Project was funded by the Fondo de Investigación Sanitario with cofunding from FEDER [PI12/00944

Desigualdades de acceso a los programas de cribado del cáncer en España y cómo reducirlas: datos de 2013 y 2020

Fundamentos: La Comisión Europea recomienda asegurar la equidad en el cribado del cáncer. El objetivo de este estudio fue conocer si existían desigualdades en el acceso a los programas de cribado del cáncer en España. Métodos: Se realizó un estudio transversal mediante encuesta dirigida a las personas responsables de los programas de cribado del cáncer de mama, colorrectal (CCR) y cérvix de las diecinueve Comunidades Autónomas (CCAA) del Estado Español en 2013 y 2020. Se recogió información sobre características organizativas, desigualdades de acceso e intervenciones para reducirlas. Se hizo un análisis descriptivo por CCAA y periodo temporal, mediante el cálculo de frecuencias y porcentajes, en función del tipo de programa (mama, CCR y cérvix). Resultados: En 2013 participaron catorce CCAA para el programa de mama, ocho para el de CCR y siete para el de cérvix, y en 2020, catorce, trece y once CCAA, respectivamente. Todos los programas de mama eran poblacionales en ambos periodos (14/14 en 2013 y 14/14 en 2020), así como los de CCR (8/8 en 2013 y 13/13 en 2020), con un aumento en el caso de los programas de cribado del cáncer de cérvix (0/7 en 2013 y 6/11 en 2020). Se identificaron en ambos periodos grupos sociales no incluidos en la población diana y grupos que, estando incluidos, participaban menos, con diferencias según el tipo de programa. Se realizaron un total de cincuenta y tres intervenciones para reducir desigualdades en el acceso (veintisiete en mama, veintidós en CCR y cuatro en cérvix), el 66% de ellas dirigidas a grupos sociales específicos (35/53). Conclusiones: Se identifican desigualdades de acceso a los programas de cribado del cáncer en España, así como intervenciones para reducirlas

Differences in breast cancer-risk factors between screen-detected and non-screen-detected cases (MCC-Spain study)

Purpose: The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69. Methods: We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase-control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method. Results: TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10-0.89), as were intermediate (OR 0.18 IC 0.07-0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03-0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08-2.36; OR 1.48 IC 1.09-2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15-2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22-2.11) and HER2+ (OR 1.59 IC 1.03-2.45) tumors. Conclusion: Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories

Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study)

Background: Some studies have reported an inverse association between type 2 diabetes mellitus (T2DM) and prostate cancer (PCa), but results on this issue are still inconsistent. In this study, we evaluate whether this heterogeneity might be related to differences in this relationship by tumour or by individual genetic susceptibility to PCa. Methods: We studied 1047 incident PCa cases and 1379 randomly selected controls, recruited in 7 Spanish provinces for the population-based MCC-Spain case-control. Tumour were classified by aggressiveness according to the International Society of Urological Pathology (ISUP), and we constructed a PCa polygenic risk score (PRS) as proxy for genetic susceptibility. The epidemiological questionnaire collected detailed self-reported data on T2DM diagnosis and treatment. The association between T2DM status and PCa was studied by fitting mixed logistic regression models, and, for its association by aggressiveness of PCa, with multinomial logistic regression models. To evaluate the possible modulator role of PRS in this relationship, we included the corresponding interaction term in the model, and repeated the analysis stratified by PRS tertiles. Results: Globally, our results showed an inverse association between T2DM and overall PCa limited to grade 1 tumours (ORISUP = 1: 0.72; 95% CI: 0.53-0.98), which could be compatible with a detection bias. However, PCa risk also varied with duration of diabetes treatment -inversely to metformin and positively with insulin-, without differences by aggressiveness. When we considered genetic susceptibility, T2DM was more strongly associated with lower PCa risk in those with lower PRS (ORtertile 1: 0.31; 95% CI: 0.11-0.87), independently of ISUP grade. Conclusions: Our findings reinforce the need to include aggressiveness and susceptibility of PCa, and T2DM treatments in the study of the relationship between both diseases

Meat Intake, Cooking Methods, Doneness Preferences and Risk of Gastric Adenocarcinoma in the MCC-Spain Study

Background: The association of meat intake with gastric adenocarcinoma is controversial. We examined the relation between white, red, and processed meat intake and gastric adenocarcinoma, considering doneness preference and cooking methods, by histological subtype and anatomical subsite. Methods: MCC-Spain is a multicase-control study that included 286 incident gastric adenocarcinoma cases and 2993 controls who answered a food-frequency questionnaire. The association of gastric adenocarcinoma with meat intake, doneness preference and cooking methods was assessed using binary multivariate logistic regression mixed models and a possible interaction with sex was considered. Multinomial logistic regression models were used to estimate risk by tumor subsite (cardia vs. non-cardia) and subtype (intestinal vs. diffuse). Sensitivity analyses were conducted comparing models with and without data on Helicobacter pylori infection. Results: The intake of red and processed meat increased gastric adenocarcinoma risk (OR for one serving/week increase (95% CI) = 1.11 (1.02;1.20) and 1.04 (1.00;1.08), respectively), specifically among men and for non-cardia and intestinal gastric adenocarcinoma. Those who consume well done white or red meat showed higher risk of non-cardia (white: RRR = 1.57 (1.14;2.16); red: RRR = 1.42 (1.00;2.02)) and intestinal tumors (white: RRR = 1.69 (1.10;2.59); red: RRR = 1.61 (1.02;2.53)) than those with a preference for rare/medium doneness. Stewing and griddling/barbequing red and white meat, and oven baking white meat, seemed to be the cooking methods with the greatest effect over gastric adenocarcinoma. The reported associations remained similar after considering Helicobacter pylori seropositivity. Conclusions: Reducing red and processed meat intake could decrease gastric adenocarcinoma risk, especially for intestinal and non-cardia tumors. Meat cooking practices could modify the risk of some gastric cancer subtypes

Beneficis i efectes adversos dels programes de cribratge de càncer colorectal a Espanya: participació i complicacions de la colonoscòpia diagnòstica

El treball que es presenta constitueix una tesi doctoral per conveni de publicacions, la línia d’investigació de la qual s'emmarca és l'estudi de l'impacte dels Programes de Prevenció de Càncer Colorectal (PPCCR). Els PPCCR han tingut una ràpida implantació a la Unió Europea des de l'any 2003 (Union, 2003), i, concretament a Espanya, s’han implantat en les diverses comunitats autònomes. Els PPCCR a Espanya van dirigits a homes i dones entre 50 i 69 anys, utilitzen com a prova de cribratge el test de sang oculta en femta (TSOF) i com a prova de confirmació diagnòstica la colonoscòpia. Aquests programes poden tenir un gran impacte en la població perquè van dirigits a un gran nombre de persones, i aquest impacte es pot traduir en beneficis i en efectes adversos. Els principals indicadors per mesurar el benefici dels PPCCR són la reducció de la mortalitat i la incidència per aquest tumor. No obstant això, per a mesurar l'impacte en terminis de reducció de mortalitat i incidència, cal que passe un llarg període amb aplicació continuada de PPCCR. L’impacte en la població està directament relacionat amb la participació, i augmentant la participació es poden augmentar els beneficis. L’impacte també es pot traduir en possibles efectes adversos del programa, la qual cosa fa que establir mecanismes que minimitzen els efectes adversos sigui fonamental. Un dels efectes adversos més greus són les complicacions en la colonoscòpia, que tenen una taxa baixa, però que cal minimitzar al màxim. Per tant, conèixer els factors que estan relacionats amb la participació i amb l'aparició de complicacions en la colonoscòpia és essencial. Aquesta investigació forma part d’un projecte d’investigació anomenat CRIBEA, en què participen 6 PPCCR implantats a les comunitats autònomes de Canàries, Catalunya, Cantabria, Comunitat Valenciana, País Basc i Regió de Múrcia. El projecte té com a objectiu analitzar el balanç entre els indicadors predictors de beneficis i d'efectes adversos dels PPCCR a Espanya. Es tracta d’un estudi retrospectiu d’una cohort d’homes i dones entre 50 i 69 anys convidats a participar en els PPCCR, des de l'inici dels programes fins al 31/12/2012, i que recull informació d’1.995.719 invitacions. La investigació està estructurada en dues parts: a la primera part s’analitzen factors que poden influir en la participació en el PPCCR, indicador clau per a obtenir beneficis a llarg termini, i, a la segona, s’analitzen factors que poden influir en l'aparició de complicacions greus a la colonoscòpia (CG), l’efecte advers més greu dels PPCCR. En aquesta investigació es van analitzar factors que influeixen en la participació en els PPCCR en un total d’1.748.853 invitacions, corresponents a les invitacions de les 3 primeres rondes de cribratge dels programes que participen en el projecte CRIBEA. Es va estudiar la influència que tenen en la participació certs factors organitzatius dels PPCCR, com el model d'enviament del TSOF, el tipus de TSOF i factors sociodemogràfics com l'edat, el sexe i l'àmbit territorial. Es van utilitzar models estadístics multivariants que tenen en compte l'estructura de mesures repetides a les dades, degut a que una persona pot tenir més d’una invitació al programa. La participació es va analitzar tenint en compte la història individual de les persones al programa, estratificat la mostra per tipologia de cribratge en cribratge inicial en la 1a invitació (persones convidades per primera volta), cribratge inicial de 2a o 3a invitació (persones convidades anteriorment, però que mai avanç havien participat), cribratge successiu regular (persones que han participat en la ronda de programa anterior) i cribratge successiu irregular (persones que han participat abans però no en la ronda anterior). Per a investigar els factors que poden influir en l'aparició de CG, es van identificar totes les CG d'entre 48.730 colonoscòpies de confirmació diagnòstica realitzades en la cohort d’homes i dones de l'estudi CRIBEA. Es defineix CG com aquella complicació que requereix hospitalització o que causa la mort per perforació, hemorràgia que necessita transfusió, síndrome vagal greu o peritonitis, i que ocorre en un termini de 0 a 30 dies des de la realització de la colonoscòpia (Segnan, 2010). Es va dissenyar un estudi de casos-controls, on els casos foren totes les CG i els controls van ser seleccionats entre les colonoscòpies que no tingueren complicació i van ser aparellats per sexe, edat, període i PPCCR. Finalment, el número de CG va ser de 161 (98 perforacions i 63 hemorràgies) i el nombre de controls va ser 314. Es va estudiar l’exposició a antecedents personals, de característiques del procediment i de troballes en la prova. Els resultats més rellevants mostren que la participació en els PPCCR està influenciada per característiques organitzatives dels PPCCR, mostrant que la probabilitat de participar és major quan la població no requereix cap acció per rebre el TSOF, independentment de la tipologia del cribratge, sent l'increment en la participació més marcat en persones amb cribratge successiu irregular. El tipus de TSOF immunològic quantitatiu també augmenta la probabilitat de participar, front a quan s’ofereix el TSOF guaiac o el TSOF immunològic qualitatiu, independentment de la tipologia de cribratge. Les persones residents en àmbit territorial rural o semi urbà mostraren més probabilitat de participar que residents en territoris urbans. Es van trobar desigualtats per edat i sexe en la participació: la participació inicial va ser major en dones i especialment en el grup d'edat més major, i la participació successiva regular va ser major en homes de més edat. En relació a les complicacions greus en la colonoscòpia, els resultats mostren que els antecedents de tractament previ de cirurgia a la pelvis o radioteràpia abdominal incrementen el risc de partir CG. S’ha mostrat associació amb la qualitat de la preparació en la colonoscòpia, sent menor el risc de patir CG quan la preparació és excel.lent. El risc de CG és major quan la colonoscòpia és terapèutica al mateix temps que diagnòstica i quan es detecten lesions més greus. Per a CG d'hemorràgia i CG tardanes es va mostrar més risc per a pacients amb tractament regular previ anticoagulant i pacients amb tractament regular antiplaquetari

Optimal cut-off value for detecting colorectal cancer with fecal immunochemical tests according to age and sex

In the fecal immunological test, a suitable cut-off value may be selected to classify results as either positive or negative. Our aim is to estimate the optimal cut-off value for detecting colorectal cancer in different age and sex groups. This is a multicentric retrospective cohort study of participants in CRC screening programs with FIT between 2006 and 2012. A total of 545,505 participations were analyzed. Cancers diagnosed outside of the program were identified after a negative test result (IC_test) up until 2014. The Wilcoxon test was used to compare fecal hemoglobin levels. ROC curves were used to identify the optimal cut-off value for each age and sex group. Screening program results were estimated for different cut-off values. The results show that the Hb concentration was higher in colorectal cancer (average = 179.6μg/g) vs. false positives (average = 55.2μg/g), in IC_test (average = 3.1μg/g) vs. true negatives (average = 0μg/g), and in men (average = 166.2μg/g) vs. women (average = 140.2μg/g) with colorectal cancer. The optimal cut-off values for women were 18.3μg/g (50-59y) and 14.6μg/g (60-69y), and 16.8μg/g (50-59y) and 19.9μg/g (60-69y) for men. Using different cut-off values for each age and sex group lead to a decrease in the IC_test rate compared to the 20μg/g cut-off value (from 0.40‰ to 0.37‰) and an increase in the false positive rate (from 6.45% to 6.99%). Moreover, test sensitivity improved (90.7%), especially in men and women aged 50-59y (89.4%; 90%) and women aged 60-69y (90.2%). In conclusion, the optimal cut-off value varies for different sex and age groups and the use of an optimal cut-off value for each group improves sensitivity and leads to a small decrease in IC_tests, but also to a larger increase in false positives.This work was supported by the Instituto de Salud Carlos III, co-founded by the European Regional Development Fund (ERDF) [PI15/02108]. https://www.isciii.es

Risk factors for severe complications of colonoscopy in screening programs

Severe complications (SC) in colonoscopy represent the most important adverse effect of colorectal cancer screening programs (CRCSP). The objective is to evaluate the risk factors for SC in colonoscopy indicated after a positive fecal occult blood test in population-based CRCSP. The SC (n = 161) identified from 48,730 diagnostic colonoscopies performed in a cohort of all the women and men invited from 2000 to 2012 in 6 CRCSP in Spain. A total of 318 controls were selected, matched for age, sex and period when the colonoscopy was performed. Conditional logistic regression models were estimated. The analysis was performed separately in groups: immediate-SC (same day of the colonoscopy); late-SC (between 1 and 30 days after); perforation; and bleeding events. SC occurred in 3.30‰ of colonoscopies. Prior colon disease showed a higher risk of SC (OR = 4.87). Regular antiplatelet treatment conferred a higher risk of overall SC (OR = 2.80) and late-SC (OR = 9.26), as did regular anticoagulant therapy (OR = 3.47, OR = 7.36). A history of pelvic-surgery or abdominal-radiotherapy was a risk factor for overall SC (OR = 5.03), immediate-SC (OR = 8.49), late-SC (OR = 4.65) and perforation (OR = 21.59). A finding of adenoma or cancer also showed a higher risk of overall SC (OR = 8.71), immediate-SC (OR = 12.67), late-SC (OR = 4.08), perforation (OR = 4.69) and bleeding (OR = 17.02). The risk of SC doesn't vary depending on the type of preparation or type of anesthesia. Knowing the clinical history of patients such as regular previous medication and history of surgery or radiotherapy, as well as the severity of the findings during the colonoscopy process could help to focus prevention measures in order to minimize SC in CRCSP.This Project was funded by the Instituto de Salud Carlos III with co-funding from FEDER [PI12/00944]