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.

Impact of different age ranges on the benefits and harms of the breast cancer screening programme by the EU-TOPIA tool.

BACKGROUND: The recommendation for the implementation of mammography screening in women aged 45-49 and 70-74 is conditional with moderate certainty of the evidence. The aim of this study is to simulate the long-term outcomes (2020-50) of using different age range scenarios in the breast cancer screening programme of the Valencia Region (Spain), considering different programme participation rates. METHODS: Three age range scenarios (S) were simulated with the EU-TOPIA tool, considering a biennial screening interval: S1, 45-69 years old (y); S2, 50-69 y and S3, 45-74 y. Simulations were performed for four participation rates: A = current participation (72.7%), B = +5%, C = +10% and D = +20%. Considered benefits: number (N°) of in situ and invasive breast cancers (BC) (screen vs. clinically detected), N° of BC deaths and % BC mortality reduction. Considered harms: N° of false positives (FP) and % overdiagnosis. RESULTS: The results showed that BC mortality decreased in all scenarios, being higher in S3A (32.2%) than S1A (30.6%) and S2A (27.9%). Harms decreased in S2A vs. S1A (N° FP: 236 vs. 423, overdiagnosis: 4.9% vs. 5.0%) but also benefits (BC mortality reduction: 27.9% vs. 30.6%, N° screen-detected invasive BC 15/28 vs. 18/25). In S3A vs. S1A, an increase in benefits was observed (BC mortality reduction: 32.2% vs. 30.6%), N° screen-detected in situ B: 5/2 vs. 4/3), but also in harms (N° FP: 460 vs. 423, overdiagnosis: 5.8% vs. 5.0%). Similar trends were observed with increased participation. CONCLUSIONS: As the age range increases, so does not only the reduction in BC mortality, but also the probability of FP and overdiagnosis.

Interval Cancer in Population-Based Colorectal Screening Programmes: Incidence and Characteristics of Tumours.

The objective of this study is to evaluate interval cancer (IC) in colorectal cancer (CRC) screening, which is CRC diagnosed in an individual after having received a negative faecal occult blood test and before the next invitation to participate in screening. A follow-up study was conducted on a cohort of participants in the first three screening rounds of four colorectal cancer screening programmes in Spain, n = 664,993. A total of 321 ICs and 2120 screen-detected cancers (SCs) were found. The IC and SC rates were calculated for each guaiac (gFOBT) or immunochemical (FIT) test. A Cox regression model was used to estimate the hazard ratios (HR) of IC risk factors. A nested case-control study was carried out to compare IC and SC tumour characteristics. The IC rate was 1.16‱ with the gFOBT and 0.35‱ with the FIT. Men and people aged 60-69 showed an increased probability of IC (HR = 1.81 and HR = 1.95, respectively). There was a decreased probability of IC in individuals who regularly participated in screening, HR = 0.62 (0.47-0.82). IC risk gradually rose as the amount of Hb detected in the FIT increased. IC tumours were in more advanced stages and of a larger size than SC tumours, and they were mostly located in the cecum. These results may play a key role in future strategies for screening programmes, reducing IC incidence.

Smoking history and breast cancer risk by pathological subtype: MCC-Spain study.

INTRODUCTION: The role of cigarette smoking on breast cancer risk remains controversial, due to its dual carcinogenic-antiestrogenic action. METHODS: In the population-based multi-case-control study (MCC-Spain), we collected epidemiological and clinical information for 1733 breast cancer cases and 1903 controls, including smoking exposure. The association with breast cancer, overall, by pathological subtype and menopausal status, was assessed using logistic and multinomial regression models. RESULTS: Smokers had higher risk of premenopausal breast cancer, particularly if they had smoked ≥30 years (AOR=1.75; 95% CI: 1.04-2.94), although most estimates did not achieve statistical significance. In contrast, among postmenopausal women, smoking was associated with lower risk of breast cancer, mainly in overweight and obese women. The strongest risk reductions were observed among postmenopausal women who had stopped smoking ≥10 years before cancer diagnosis, particularly for HER2+ tumors (AOR=0.28; 95% CI: 0.11-0.68); p for heterogeneity = 0.040). Also, those who had smoked <10 pack-years (AOR=0.68; 95% CI: 0.47-0.98) or 10-25 pack-years (AOR=0.62; 95% CI: 0.42-0.92) during their lifetime were at a reduced risk of all breast cancer subtypes (p for heterogeneity: 0.405 and 0.475, respectively); however, women who had smoked more than 25 pack-years showed no reduced risk. CONCLUSIONS: Menopausal status plays a key role in the relationship between tobacco and breast cancer for all cancer subtypes. While smoking seems to increase the risk in premenopausal woman, it might be associated to lower risk of breast cancer among postmenopausal women with excess weight.

Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase-control study (MCC-Spain).

Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (

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.

Chronic metformin intake and gastric cancer: A pooled analysis within the Stomach cancer Pooling (StoP) Project.

INTRODUCTION: The association between chronic use of metformin and risk of gastric cancer (GC) has been investigated with contradicting results. We aimed to study the association between chronic use of metformin and GC by using data from the Stomach cancer Pooling (StoP) Project, an epidemiological consortium of case-control studies on GC. METHODS: Data from three studies of the StoP Project with available information on metformin intake were analyzed. Multivariable logistic regression models were used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between chronic use of metformin and GC risk. Analyses were adjusted for sex, age, socioeconomic status, body mass index, smoking status, alcohol drinking status, and history of diabetes. Study-specific ORs and 95% CIs were then pooled with a random-effects model. The dose-response relationship between the duration of metformin intake and GC was assessed with a one-stage logistic model, and the duration of intake was modelled using second-order fractional polynomials. RESULTS: The OR of GC in metformin users versus non-users was 1.01 (95% CI=0.61, 1.67). The association between metformin and GC did not change among different strata of study participants' characteristics or when restricting the analyses to those with a history of diabetes. The dose-response analysis showed a slightly reducing trend in the OR of GC and a borderline significant association with increasing duration of metformin intake. CONCLUSIONS: The results of our study do not clearly support an association between chronic use of metformin and GC, warranting further research.

Toenail zinc as a biomarker: Relationship with sources of environmental exposure and with genetic variability in MCC-Spain study.

BACKGROUND: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn. OBJECTIVES: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism. METHODS: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn. RESULTS: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1-13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3-16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0-9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women. DISCUSSION: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn.