Leisure-time physical activity and gastric cancer risk: A pooled study within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Although physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully understood. This study aims to provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC. METHODS: Six case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. We performed stratified analyses according to demographic, lifestyle and clinical covariates. RESULTS: The meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]) and for control population-based studies (high vs low level: OR 0.79 [95%CI 0.68-0.93]). CONCLUSIONS: No association was found between leisure time PA and GC, apart from a slight suggestion of decreased risk below age 55 and in control population-based studies. These results may reflect specific characteristics of GC at a younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC The different distribution of PA levels among hospitalized controls could have led to an underestimated effect of PA on GC risk.

Relationship between Aldehyde Dehydrogenase, PD-L1 and Tumor-Infiltrating Lymphocytes with Pathologic Response and Survival in Breast Cancer.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cancer stem cell (CSC) marker related to clinical outcomes in breast cancer (BC). The aim of this study was to analyze the relationship between ALDH1A1, programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2-positive (HER2+) BC tumors, and its association with clinicopathological characteristics and outcomes. A retrospective, historical cohort study of patients diagnosed with early or locally advanced BC treated with neoadjuvant chemotherapy was conducted. ALDH1A1, PD-L1 expression and TILs were assessed using immunohistochemistry. A total of 75 patients were analyzed (42.7% TN, 57.3% HER2+ tumors). ALDH1A1+ was related to HTILs (p = 0.005) and PD-L1+ tumors (p = 0.004). ALDH1A1+ tumors presented higher CD3+ (p = 0.008), CD4+ (p = 0.005), CD8+ (p = 0.003) and CD20+ (p = 0.006) TILs. ALDH1A1+ (p = 0.018), PD-L1+ (p = 0.004) and HTILs (p < 0.001) were related to smaller tumors. ALDH1A1+ was related to pathologic complete response (pCR) (p = 0.048). At the end of the follow-up (54.4 [38.3−87.6] months), 47 patients (62.7%) remained disease-free, and 20 (26.7%) had died. HTILs were related to improved disease-free survival (p = 0.027). ALDH1A1+ was related to PD-L1+ and HITLs, that might be related to higher pCR rates with neoadjuvant therapy.

Dietary Constituents: Relationship with Breast Cancer Prognostic (MCC-SPAIN Follow-Up).

The aim of this study was to characterize the relationship between the intake of the major nutrients and prognosis in breast cancer. A cohort based on 1350 women with invasive (stage I-IV) breast cancer (BC) was followed up. Information about their dietary habits before diagnosis was collected using a semi-quantitative Food Frequency Questionnaire. Participants without FFQ or with implausible energy intake were excluded. The total amount consumed of each nutrient (Kcal/day) was divided into tertiles, considering as "high intakes" those above third tertile. The main effect studied was overall survival. Cox regression was used to assess the association between death and nutrient intake. During a median follow-up of 6.5 years, 171 deaths were observed. None of the nutrients analysed was associated with mortality in the whole sample. However, in normal-weight women (BMI 18.5-25 kg/m2) a high intake of carbohydrates (≥809 Kcal/day), specifically monosaccharides (≥468 Kcal/day), worsened prognostic compared to lowest (≤352 Kcal/day). Hazard Ratios (HRs) for increasing tertiles of intake were HR:2.22 95% CI (1.04 to 4.72) and HR:2.59 95% CI (1.04 to 6.48), respectively (p trend = 0.04)). Conversely, high intakes of polyunsaturated fats (≥135 Kcal/day) improved global survival (HR: 0.39 95% CI (0.15 to 1.02) p-trend = 0.05) compared to the lowest (≤92.8 kcal/day). In addition, a protective effect was found substituting 100 kcal of carbohydrates with 100 kcal of fats in normal-weight women (HR: 0.76 95% CI (0.59 to 0.98)). Likewise, in premenopausal women a high intake of fats (≥811 Kcal/day) showed a protective effect (HR:0.20 95% CI (0.04 to 0.98) p trend = 0.06). Finally, in Estrogen Receptors (ER) negative tumors, we found a protective effect of high intake of animal proteins (≥238 Kcal/day, HR: 0.24 95% CI (0.06 to 0.98). According to our results, menopausal status, BMI and ER status could play a role in the relationship between diet and BC survival and must be taken into account when studying the influence of different nutrients.

Analysis of Killer Immunoglobulin-Like Receptor Genes in Colorectal Cancer.

Natural killer cells (NK cells) play a major role in the immune response to cancer. An important element of NK target recognition is the binding of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs). Colorectal carcinoma (CRC) is one of the most common types of inflammation-based cancer. The purpose of the present study was to investigate the presence of KIR genes and HLA class I and II alleles in 1074 CRC patients and 1272 controls. We imputed data from single-nucleotide polymorphism (SNP) Illumina OncoArray to identify associations at HLA (HLA-A, B, C, DPB1, DQA1, DQB1, and DRB1) and KIRs (HIBAG and KIR*IMP, respectively). For association analysis, we used PLINK (v1.9), the PyHLA software, and R version 3.4.0. Only three SNP markers showed suggestive associations (p < 10-3; rs16896742, rs28367832, and rs9277952). The frequency of KIR2DS3 was significantly increased in the CRC patients compared to healthy controls (p < 0.005). Our results suggest that the implication of NK cells in CRC may not act through allele combinations in KIR and HLA genes. Much larger studies in ethnically homogeneous populations are needed to rule out the possible role of allelic combinations in KIR and HLA genes in CRC risk.

Colorectal cancer, sun exposure and dietary vitamin D and calcium intake in the MCC-Spain study.

OBJECTIVES: To explore the association of colorectal cancer with environmental solar radiation and sun exposure behavior, considering phenotypic variables (eye color, hair color and skin phenotype), dietary intake of vitamin D and calcium, and socio-demographic factors. STUDY DESIGN: Multicenter population-based frequency matched case-control study in Spain (MCC-Spain), with 2140 CRC cases and 3950 controls. METHODS: Data were obtained through personal interviews using a structured epidemiological questionnaire that included socio-demographic data, residential history, environmental exposures, behavior, phenotypic and dietary information. An environmental-lifetime sun exposure score was constructed combining residential history and average daily solar radiation, direct and diffuse. Logistic regression was used to explore the association between different variables. A structural equation model was used to verify the associations of the conceptual model. RESULTS: We found a lower risk of CRC in subjects frequently exposed to sunlight during the previous summer and skin burning due to sun exposure. No association was observed in relation to the residential solar radiation scores. Subjects with light eye or light hair colors had a lower risk of CRC that those with darker colors. Dietary calcium and vitamin D were also protective factors, but not in the multivariate model. The structural equation model analysis suggested that higher sun exposure was associated with a decreased risk of CRC, as well as dietary intake of calcium and vitamin D, and these factors are correlated among themselves and with environmental solar radiation and skin phenotypes. CONCLUSION: The results agree with previous observations that sun exposure, dietary vitamin D and calcium intake, and serum 25(OH)D concentration reduce the risk of CRC and indicate that these factors may be relevant for cancer prevention.

The Use of Antihypertensive Medication and the Risk of Breast Cancer in a Case-Control Study in a Spanish Population: The MCC-Spain Study.

INTRODUCTION: The evidence on the relationship between breast cancer and different types of antihypertensive drugs taken for at least 5 years is limited and inconsistent. Furthermore, the debate has recently been fueled again with new data reporting an increased risk of breast cancer among women with a long history of use of antihypertensive drugs compared with nonusers. METHODS: In this case-control study, we report the antihypertensive drugs-breast cancer relationship in 1,736 breast cancer cases and 1,895 healthy controls; results are reported stratifying by the women's characteristics (i.e., menopausal status or body mass index category) tumor characteristics and length of use of antihypertensive drugs. RESULTS: The relationship among breast cancer and use of calcium channel blockers (CCB) for 5 or more years had odds ratio (OR) = 1.77 (95% CI, 0.99 to 3.17). Stratifying by BMI, the OR increased significantly in the group with BMI ≥ 25 (OR 2.54, 95% CI, 1.24 to 5.22). CCBs were even more strongly associated with more aggressive tumors, (OR for invasive tumors = 1.96, 95% CI = 1.09 to 3.53; OR for non ductal cancers = 3.97, 95% CI = 1.73 to 9.05; OR for Erbb2+ cancer = 2.97, 95% CI: 1.20 to 7.32). On the other hand, premenopausal women were the only group in which angiotensin II receptor blockers may be associated with breast cancer (OR = 4.27, 95% CI = 1.32 to 13.84) but this could not be identified with any type or stage. Use of angiotensin-converting-enzyme inhibitors, beta blockers and diuretics were not associated with risk. CONCLUSIONS: In this large population-based study we found that long term use of calcium channel blockers is associated with some subtypes of breast cancer (and with breast cancer in overweight women).

Perinatal and childhood factors and risk of breast cancer subtypes in adulthood.

BACKGROUND: Accumulated exposure to hormones and growth factors during early life may influence the future risk of breast cancer (BC). This study examines the influence of childhood-related, socio-demographic and anthropometric variables on BC risk, overall and by specific pathologic subtypes. METHODS: This is a case-control study where 1539 histologically-confirmed BC cases (23-85 years) and 1621 population controls, frequency matched by age, were recruited in 10 Spanish provinces. Perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with BC risk, globally and according to menopausal status and pathologic subtypes, was evaluated using logistic and multinomial regression models, adjusting for tumor specific risk factors. RESULTS: Birth characteristics were not related with BC risk. However, women with high socioeconomic level at birth presented a decreased BC risk (OR=0.45; 95% CI=0.29-0.70), while those whose mothers were aged over 39 years at their birth showed an almost significant excess risk of hormone receptor positive tumors (HR+) (OR=1.35; 95% CI=0.99-1.84). Women who were taller than their girl mates before puberty showed increased postmenopausal BC risk (OR=1.26; 95% CI=1.03-1.54) and increased HR+ BC risk (OR=1.26; 95% CI=1.04-1.52). Regarding prepubertal weight, while those women who were thinner than average showed higher postmenopausal BC risk (OR=1.46; 95% CI=1.20-1.78), associated with HR+ tumors (OR=1.34; 95% CI=1.12-1.61) and with triple negative tumors (OR=1.56; 95% CI=1.03-2.35), those who were heavier than average presented lower premenopausal BC risk (OR=0.64; 95% CI=0.46-0.90) and lower risk of epidermal growth factor receptor positive tumors (OR=0.61; 95% CI=0.40-0.93). CONCLUSION: These data reflect the importance of hormones and growth factors in the early stages of life, when the mammary gland is in development and therefore more vulnerable to proliferative stimuli.

[UNIHCOS Project: dynamic cohort of Spanish college students to the study of drug and other addictions]. / Proyecto UNIHCOS: cohorte dinámica de estudiantes universitarios para el estudio del consumo de drogas y otras adicciones.

The University stage gives rise to social and personal changes as the independence of the nuclear family and the increased responsibilities that are related to the acquisition and/or consolidation of life styles and habits that may determine the future health status. Inadequate nutrition, a high level of inactivity, risky sexual behavior, abuse of new technologies or starting consumption of legal and illegal drugs, are among the most significant risk behaviors in this phase. In order to know how to set and / or consolidate the habits and lifestyles in the university stage and health effects in the future, to born the uniHcos project. It is a dynamic cohort of university students who join the project during the first academic year and will be followed during their stay at college and working life. The follow-up will be biennially and for the capture and the information collection will be used on-line technologies. This paper aims to show the uniHcos project to the scientific community as well as present preliminary results found so far in the two cohorts established since 2011.

[Municipal distribution and trend of the incidence of stomach cancer in the health area of León, Spain (1994-2008)]. / Tendencia y distribución municipal de la incidencia de cáncer de estómago en el área de salud de León (1994-2008).

BACKGROUND: Stomach cancer is common and has a high mortality rate. The aim of this study was to analyze the incidence and trend of gastric cancer in the health area of León. METHODS: We designed an observational descriptive study that included patients enrolled in the Hospital Tumor Registry of the Centro Asistencial Universitario de León with a diagnosis of malignant neoplasm of the stomach (ICD 9-151, ICD10-C16) between 01/01/1994 and 12/31/2008 and resident in the health area of León. The population supplied by Spain's National Institute of Statistics was used as the denominator. The time trend was evaluated with a Poisson regression model. To study the spatial distribution, we estimated municipal relative risks (RR) smoothed by fitting the Besag, York and Mollié model and the posterior probability (PP) of RR>1 using bayesian methods. RESULTS: A total of 1680 cases were included. The average crude incidence rate was 40.0 new cases per 100,000 in men and 23.5 for women. The incidence decreased by 1.4% per year (men: 1.2%, women: 1.8%). The age adjusted rates (European standard population) decreased from 26.9 (1994-6) to 22.2 (2006-8) new cases per 100,000 population in men and from 13.3 to 9.5 in women. Three geographical areas showed a RR excess with a PP higher than 0.9. CONCLUSIONS: The observed rates are among the highest in Spain and their declining trend is lower than expected. Some municipalities had an excess risk.

[Municipal distribution and trends in the incidence of colorectal cancer in the health area of Leon (1994-2008)]. / Tendencia y distribución municipal de la incidencia de cáncer colorrectal en el área de salud de León (1994-2008).

BACKGROUND: There is an excess incidence of colorectal cancer (CRC) and mortality from this disease in the health area of Leon. The aim of the present study was to determine trends in CRC and its geographical distribution. METHODS: Cases included in the Hospital Registry of Tumors of the Centro Asistencial Universitario de León from 1994-2008 and occurring in patients residing in the health area of Leon were studied. Time trends were evaluated with a Poisson regression model. To analyze geographical distribution, the smoothed relative risks (RR) of the municipalities adjusted by the Besag, York and Mollié model were calculated, and their subsequent probability of an RR>1 (PP) was calculated using Bayesian methods. RESULTS: A total of 4,136 cases were included. Rates standardized to the European standard population ranged from 49.6 (1994-6) to 63.5 new cases per 100,000 inhabitants in men (2006-8) and from 29.6 to 33.8 in women. An annual 2% increase was found for all localizations, ranging from 1.8% in the rectum to 3.6% in the proximal colon. In all localizations, the increase was greater in men than in women. Several municipalities in the health area of Leon showed an excess risk. The geographical pattern observed was due especially to the distribution of colon cancer. CONCLUSIONS: The incidence rates observed were high and were increasing. Special attention should be paid to CRC in the health area of Leon, mainly in the municipalities with excess risk.