Flavonoids and the Risk of Gastric Cancer: An Exploratory Case-Control Study in the MCC-Spain Study

Several epidemiological studies have investigated the association between the dietary flavonoid intake and gastric cancer (GC) risk; however, the results remain inconclusive. Investigating the relationship between the different classes of flavonoids and the histological types and origin of GC can be of interest to the research community. We used data from a population-based multi-case control study (MCC-Spain) obtained from 12 different regions of Spain. 2700 controls and 329 GC cases were included in this study. Odds ratios (ORs) were calculated using the mixed e ects logistic regression considering quartiles of flavonoid intakes and log2. Flavonoid intake was associated with a lower GC risk (ORlog2 = 0.76; 95% CI = 0.65–0.89; ORq4vsq1 = 0.60; 95%CI = 0.40–0.89; ptrend = 0.007). Inverse and statistically significant associations were observed with anthocyanidins, chalcones, dihydroflavonols and flavan-3-ols. The isoflavanoid intake was positively associated with higher cancer risk, but without reaching a statistical significance. In general, no differences were observed in the GC risk according to the location and histological type. The flavonoid intake seems to be a protective factor against GC within the MCC-study. This effect may vary depending on the flavonoid class but not by the histological type and location of the tumor. Broader studies with larger sample size and greater geographical variability are necessary.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on 11 October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)), by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation – grant GCTRA18022MORE, by the Catalan Government- Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya

Agreement among Mediterranean diet pattern adherence indexes : MCC-Spain study

There are many different methods used to measure the degree of adherence to a Mediterranean diet (MD), limiting comparison and interpretation of their results. The concordance between different methodologies has been questioned and their evaluation recommended. The aim of this study was to evaluate the agreement among five indexes that measure adherence to a Mediterranean dietary pattern. The study population included healthy adults selected in the Multi-Case Control Spain (MCC-Spain) study recruited in 12 provinces. A total of 3640 controls were matched to cases by age and sex. To reach the aim, the following scores of adherence to a Mediterranean dietary pattern were calculated: Mediterranean diet score (MDS), alternative Mediterranean diet (aMED), relative Mediterranean diet (rMED), dietary score (DS) and literature-based adherence score (LBAS). The relative frequency of subjects with a high level of adherence to a MD varied from 22% (aMED index) to 37.2% (DS index). Similarly, a high variability was observed for the prevalence of a low level of MD: from 24% (rMED) to 38.4% (aMED). The correlation among MDS, aMED and rMED indexes was moderate, except for MDS and aMED with a high coefficient of correlation 0.75 (95% CI 0.74–0.77). The Cohen’s Kappa coefficient among indexes showed a moderate–fair concordance, except for MDS and aMED with a 0.56 (95% CI 0.55–0.59) and 0.67 (95% CI 0.66–0.68) using linear and quadratic weighting, respectively. The existing MD adherence indexes measured the same, although they were based on different constructing algorithms and varied in the food groups included, leading to a different classification of subjects. Therefore, concordance between these indexes was moderate or low.The authors thank Ingrid de Ruiter, MBChB PhD for English language editing and support. We thank all subjects who participated in the study and all MCC-Spain collaborators

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 noncardia 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.FEDER funds-a way to build Europe PI08/1770 PI09/00773 PS09/01286 PI09/1903 PI09/1662 PI09/2078 PI11/01403Spanish Government IJCI-2014-20900Instituto de Salud Carlos III API 10/09Junta de Castilla y Leon LE22A10-2Instituto de Salud Carlos IIICIBER of Epidemiology and Public Health (CIBERESP)Catalan Government DURSI 2014SGR647 2014SGR756Junta de Andalucia 2009-S0143Conselleria de Sanitat of the Generalitat Valenciana AP061/10University of Oviedo, IUOPAFundacion Caja de AsturiasSpanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa" Program CEX2018-000806-SGeneralitat de Catalunya through the CERCA ProgramMinistry of Economy and Competitiveness (Bolsa de Ampliacion de Estudios. Accion Estrategica en Salud del Plan Nacional I+D+i)Spanish Association Against Cancer Scientific Foundation (AECC) POSTD037OBONInstituto de Salud Carlos III European Commission RD09/0076/00036 RD 09 0076/00021 RD09 0076/00058Catalan Institute of OncologyISCIII BiobankIUOPA Biobank of the University of OviedoInstituto de Salud Carlos II

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

The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034), by the Fundaci on Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consor- tium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad [MINECO] through the Instituto de Salud Carlos III [ISCIII] and Red Temática de Investigaci on del Cáncer [RTICC] del ISCIII [RD12/0036/0036]), by the Junta de Castilla y Le on (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Regi on de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723, 2014SGR850, 2017SGR1085, 2021SGR01354 by the Fundaci on Caja de Ahorros de Asturias and by the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. Anna Palomar-Cros is supported by a MINECO (Spanish Ministry of Econ- omy) fellowship (PRE2019-089038). Camille Lassale is supported by a Ramon y Cajal Fellowship RYC2020-029599 funded by MCIN (Spanish Ministry of Science and Innovation) and EI FSE “Invest in your future”.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 (<third quartile) and high consumers (≥ third quartile) vs non consumers (reference category), distinguishing aspartame-containing products and other AS. Unconditional logistic regression models were used to estimate adjusted OR and 95%CI, and results were stratified by diabetes status. Overall, we found no associations between the consumption of aspartame or other AS and cancer. Among participants with diabetes, high consumption of other AS was associated with colorectal cancer (OR = 1.58, 95% CI 1.05-2.41, P trend = .03) and stomach cancer (OR = 2.27 [0.99-5.44], P trend = .06). High consumption of aspartame, was associated with stomach cancer (OR = 2.04 [0.7-5.4], P trend = .05), while a lower risk was observed for breast cancer (OR = 0.28 [0.08-0.83], P trend = .03). In some cancers, the number of cases in participants with diabetes were small and results should be interpreted cautiously. We did not find associations between use of AS and cancer, but found associations between high consumption of aspartame and other AS and different cancer types among participants with diabetes.AGAUR 2014SGR850, 2017SGR1085, 2017SGR723, 2021SGR01354Catalan Government‐Agency for Management of University and Research GrantsCentro de Excelencia Severo Ochoa 2019‐2023Consejería de Salud of the Junta de Andalucía PI‐0306‐2011Consejería de Sanidad de la Región de MurciaRegional Government of the Basque CountryConselleria de Sanitat of the Generalitat Valenciana 2010ACUP 00310, AP_061/10EI FSEEuropean Commission grants FOOD-CT- 2006-036224-HIWATEFundación Caja de Ahorros de AsturiasFundación Marqués de Valdecilla API 10/09Generalitat de CatalunyaICGC International Cancer Genome Consortium CLLInstituto de Salud Carlos III‐FEDER PI08/0533, PI08/1359, PI08/1770, PI11/00226, PI11/01403, PI11/01810, PI11/01889, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034, PS09/00773, PS09/01286, PS09/01662, PS09/02078Junta de Castilla y León LE22A10‐2MCINMINECORTICC RD12/0036/0036Red Temática de Investigación del CáncerSpanish Association Against Cancer (AECC) Scientific FoundationSpanish Ministry of Economy PRE2019‐089038Spanish Ministry of Science and InnovationUniversity of Ovied

Psychological Distress, Family Support and Employment Status in First-Year University Students in Spain

Mental disorders are consistently and closely related to psychological distress. At the start of the university period, the relationship between a student’s psychological distress, family support, and employment status is not well-known. The aims of this study were: To determine the prevalence of psychological distress in first-year university students and to analyze its relationship with family support and the student’s employment status. Data from 4166 first-year university students from nine universities across Spain were considered. The prevalence of psychological distress was obtained using the GHQ-12, a valid and reliable screening tool to detect poor mental health. To analyze the relationship between psychological distress, family support, and employment status, logistic regression models were fitted. Regarding the prevalence found, 46.9% of men and 54.2% of women had psychological distress. In both genders, psychological distress levels increased as family support decreased. Among women, psychological distress was associated with their employment status. The prevalence of psychological distress among first-year university students in Spain is high. In addition, family support, and employment status for women, could be factors to take into account when developing psychological distress prevention strategies at the beginning of the university period.This study was funded by the National Drug Plan from the Ministry of Health, Social Services and Equality of Spain (Codes: 2010|145 and 2013|034)

Ejaculation Frequency and Prostate Cancer: CAPLIFE Study

Purpose To evaluate the association between ejaculation frequency (EF) during four stages of life and prostate cancer (PCa) according to tumor aggressiveness, PCa stage, and urinary symptomatology. Materials and Methods A total of 456 incident PCa cases histologically confirmed, and 427 controls aged 40–80 years from the CAPLIFE study were analyzed. This study is a population-based case-control study carried out in the south of Spain. Average EF was measured for: (1) 20s, (2) 30s, (3) 40s, and (4) one year before the interview. EF was categorized into: (1) 0–3, (2) 4, and (3) >4 ejaculations/month. Sociodemographic, lifestyle, and medical information were also collected. To estimate the association between EF and PCa, adjusted ORs (aORs) and 95% CIs were calculated by logistic regression models. Results A year before the interview, PCa cases ejaculated less frequently than the controls. An inverse association was observed between the EF a year before and PCa, aOR=1.64 (95% CI 1.03–2.61) for men with 4 ejaculations/month, and aOR=2.38 (95% CI 1.57–3.60) for men with 0–3 ejaculations/month, compared to men with >4. The association was higher for cases with ISUP 3–5 (aOR=2.76 [95% CI 1.34–5.67] for men with 0–3 ejaculations/month) or with a locally advanced-metastatic tumor (aOR=4.70 [95% CI 1.55–14.29]). Moreover, men with moderate urinary symptoms and 0–3 ejaculations/month had the highest risk, aOR=3.83 (95% CI 1.84–7.95). Conclusions A low EF could be associated with a higher risk of PCa, especially for cases with ISUP 3–5 or with a locally advanced-metastatic tumor.Regional Ministry of Health and Families of Andalusia/Consejería de Salud y Familias, Junta de Andalucía (PI-0514-2016)

Factors associated with the development of second primary tumours in head and neck cancer patients

ACKNOWLEDGEMENTS Funding for open access charge: Universidad de Granada/CBUA. Study concepts: RBR. Study design: RBR, ISB, PR. Acquisition of data: RM, COR, ROR, MLL. Data analysis and interpretation: RBR, ISB, PR y JPA. Manuscript preparation: ISB, PR, RBR. Manuscript review: ISB, PR, RM, COR, ROR, MLL, JPA, RBR. Manuscript final approval: ISB, PR, RM, COR, ROR, MLL, JPA, RBR. Being accountable for all aspects of the work: ISB, PR, RM, COR, ROR, MLL, JPA, RBR.Introduction: The development of second primary tumours (SPTs) is one of the main causes of low survival in patients with head and neck cancer (HNC). The aim of this study was to review the evidence about factors associated with developing SPTs in patients with HNC. Methods: An updated systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and the search was performed in Pubmed and Scopus. Only original articles with a cohort or case-control design were included. Article quality was assessed with the Newcastle-Ottawa scale. Results: Thirty-six and two case-control studies were included, with quality medium (n = 5) to high (n = 33). Tobacco showed a significant association with SPT development, with risks ranging from 1.41 (95%CI: 1.04-1.91) to 5.52 (95%CI: 2.91-10.49). Regarding alcohol, risks ranged from 1.46 (95%CI: 1.12-1.91) to 21.3 (95%CI: 2.9-156). Location of the index tumour in the hypopharynx/oropharynx, absence of human papillomavirus and presence of a premalignant lesion also increased the risk of SPTs. More controversy was found for sex, age and other clinical factors of the tumour. Conclusion: Toxic lifestyle habits and clinical factors were associated with the risk of SPTs in HNC patients. These findings may improve individualised prevention strategies in its follow-up.Spanish Ministry of Science, Innovation and Universities through the grant ‘Ramon y Cajal’Universidad de Granada/CBUA (Funding for open access charge

Dietary Diversity and Prostate Cancer in a Spanish Adult Population: CAPLIFE Study

The authors wish to thank all subjects who participated in the study as well as all CAPLIFE collaborators. The authors also thank Ingrid de Ruiter for English editing support.Dietary diversity (DD) is a key component of a high-quality diet, providing the adequate nutrient requirements. However, the role of DD on prostate cancer (PCa) is still uncertain. The aim of this study was to evaluate the relationship between DD, adequate nutrient intake and PCa, according to the aggressiveness of the tumor. The CAPLIFE (CAP: prostate cancer; LIFE: lifestyles) study is a population-based case-control study including a total of 402 incident PCa cases and 302 controls. The DD score (DDS), adjusted by total energy intake, was collected through a validated food frequency questionnaire. Nutrient adequacy was defined according to European Dietary Recommendation Intake for men. The aggressiveness of PCa was determined according to the International Society of Urology Pathology classification. The association between DDS, nutrient intake and PCa was assessed by logistic regression models with adjustment for potential confounding factors. DDS was similar for PCa cases and controls, independent of PCa aggressiveness. According to each food group DDS, the protein group showed the highest mean score in all the subgroups analyzed. However, no differences were observed for each of the DDS components. The DDS, the variety of the group’s food intake, and the adequate nutrient intake, were not associated with PCa.Regional Ministry of Health of Andalusia (Consejeria de Salud de la Junta de Andalucia) PI-0514-201

Perinatal and Maternal Outcomes According to the Accurate Term Antepartum Ultrasound Estimation of Extreme Fetal Weights

(1) Background: The accuracy of ultrasound estimation of fetal weight (EFW) at term may be useful in addressing obstetric complications since birth weight (BW) is a parameter that represents an important prognostic factor for perinatal and maternal morbidity. (2) Methods: In a retrospective cohort study of 2156 women with a singleton pregnancy, it is verified whether or not perinatal and maternal morbidity differs between extreme BWs estimated at term by ultrasound within the seven days prior to birth with Accurate EFW (difference < 10% between EFW and BW) and those with Non-Accurate EFW (difference ≥ 10% between EFW and BW). (3) Results: Significantly worse perinatal outcomes (according to different variables such as higher rate of arterial pH at birth < 7.20, higher rate of 1-min Apgar < 7, higher rate of 5-min Apgar < 7, higher grade of neonatal resuscitation and need for admission to the neonatal care unit) were found for extreme BW estimated by antepartum ultrasounds with Non-Accurate EFW compared with those with Accurate EFW. This was the case when extreme BWs were compared according to percentile distribution by sex and gestational age following the national reference growth charts (small for gestational age and large for gestational age), and when they were compared according to weight range (low birth weight and high birth weight). (4) Conclusions: Clinicians should make a greater effort when performing EFW by ultrasound at term in cases of suspected extreme fetal weights, and need to take an increasingly prudent approach to its management

Replacement of watching television with physical activity and the change in gestational diabetes mellitus risk: A case–control study

Objective: To evaluate the effect of replacing 1 h/week of watching television with 1 h/week of light to moderate (LMPA) or vigorous physical activity (VPA) before and during pregnancy on the risk of gestational diabetes mellitus (GDM). Methods: A case–control study was conducted in pregnant women. Physical activity and television watching before and during pregnancy were assessed using the Paffenbarger Physical Activity Questionnaire. Each type of activity was classified according to intensity (metabolic equivalent of task; MET): less than 6 METs is LMPA, 6 METs or more is VPA. The duration of physical activity and watching television was calculated, and logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals for their association with GDM risk. The isotemporal substitution model was used to calculate the effect of replacing 1 h/week of watching television with the same duration of physical activity. Results: The GDM cases (n = 290) spent less time performing VPA than controls without GDM (n = 1175) and more time watching television during pregnancy (P < 0.05). During pregnancy, the risk of GDM increased for each hour of watching television (aOR = 1.02; 95% confidence interval 1.00–1.03). Women who spent more time watching television during pregnancy were likely to develop GDM (aOR>14 h/week vs. 0–6 h/week = 2.03; 95% confidence interval 1.35–3.08). Replacing 1 h/week of watching television with 1 h/week of VPA during pregnancy could decrease the chance of developing GDM (aOR = 0.66; 95% confidence interval 0.43–1.00). Conclusions: A simple change of 1 h/week of watching television for 1 h/week of VPA in pregnant women may reduce the risk of GDM considerablyFIS Scientific Research Project, Grant/ Award Number: PI 03/1207Junta de Andalucía Excellence Project, Grant/ Award Number: CTS 05/942Universidad de Granada/CBU