Suchergebnisse

Samples: Biological samples were stored at the biobanks supported by Instituto de Salud Carlos III- FEDER: Parc de Salut MAR Biobank (MARBiobanc) (RD09/0076/00036), "Biobanco La Fe" (RD 09 0076/00021) and FISABIO Biobank (RD09 0076/00058), and also at the Public Health Laboratory from Gipuzkoa, the Basque Biobank, the ICOBIOBANC (sponsored by the Catalan Institute of Oncology), the IUOPA Biobank from the University of Oviedo and the ISCIII Biobank. Genotyping: SNP genotyping services were provided by the Spanish "Centro Nacional de Genotipado" (CEGEN-ISCIII)". ; Background: Reproductive factors are well known risk factors for breast cancer; however, little is known about how genetic variants in hormonal pathways interact with that relationship. Methods: One thousand one hundred thirty nine cases of breast cancer in women and 1322 frequency-matched controls were compared. Genetic variants in hormonal pathways (identified in the Kyoto Encyclopedia of Genes and Genomes) were screened according to their relationship with breast cancer using the Cochran-Armitage statistic. Information on reproductive factors was obtained using a face-to-face questionnaire. The interaction among the selected genetic variants and reproductive factors was tested with logistic regression. Results: Concerning C allele in rs2229712, compared to nulliparity in non-carriers the ORs for 1–2 and > 2 deliveries were 0.48 (0.28–0.81) and 0.34 (0.19–0.59), and in C carriers they were 0.92 (0.42–1.98) and 0.71 (0.31–1.61). Similar results were found in women carrying the C allele in rs1269851. Carriers of Allele T in rs35652107 and allele C in rs6018027 had the delivery number effect more pronounced. Conclusions: The number of deliveries had a dose-response protective effect on breast cancer; women carrying C allele in rs2229712 did not benefit from this protective effect. ; This work was partially funded by the "Accion Transversal del Cancer", approved by the Spanish Ministry Council on the 11th October 2007; The Instituto de Salud Carlos III-FEDER [PI08/1770, PI08/0533, PI08/1359, PI09/ 00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-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]; The Fundación Marqués de Valdecilla [API 10/09]; 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)); The Junta de Castilla y León [LE22A10–2]; The Consejería de Salud of the Junta de Andalucía [2009-S0143]; The Conselleria de Sanitat of the Generalitat Valenciana [AP_061/10]; The Recercaixa [2010ACUP 00310]; The Regional Government of the Basque Country; The Consejería de Sanidad de la Región de Murcia; The European Commission [grants FOOD-CT-2006-036224-HIWATE]; The Spanish Association Against Cancer (AECC) Scientific Foundation; The Catalan Government DURSI [grant 2014SGR647]; The Fundación Caja de Ahorros de Asturias; and the University of Oviedo.

ABSTRACT: Background: The association between socioeconomic level and reproductive factors has been widely studied. For example, it is well known that women with lower socioeconomic status (SES) tend to have more children, the age at first-born being earlier. However, less is known about to what extent the great socioeconomic changes occurred in a country (Spain) could modify women reproductive factors. The main purpose of this article is to analyze the influence of individual and contextual socioeconomic levels on reproductive factors in Spanish women, and to explore whether this influence has changed over the last decades. Methods: We performed a cross-sectional design using data from 2038 women recruited as population-based controls in an MCC-Spain case-control study. Results: Higher parent's economic level, education level, occupational level and lower urban vulnerability were associated with higher age at first delivery and lower number of pregnancies. These associations were stronger for women born after 1950: women with unfinished primary education had their first delivery 6 years before women with high education if they were born after 1950 (23.4 vs. 29.8 years) but only 3 years before if they were born before 1950 (25.7 vs. 28.0 years). For women born after 1950, the number of pregnancies dropped from 2.1 (unfinished primary school) to 1.7 (high education), whereas it remained almost unchanged in women born before 1950. Conclusions: Reproductive behavior was associated with both individual and area-level socio-economic indicators. Such association was stronger for women born after 1950 regarding age at first delivery and number of pregnancies and for women born before 1950 regarding consumption of hormonal contraceptives or postmenopausal therapy. ; This work was supported by the 'Acción Transversal del Cancer', approved by the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III, co-founded by FEDER funds –'a way to build Europe' (grants PI08/1770, PI08/0533, PI08/1359, PI09/00773, PI09/01286, PI09/01903, PI09/ 02078, PI09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/ 02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/ 01219, PI14/00613, and PI15/00069). Support was also provided by the Fundación Marqués de Valdecilla (grant API 10/09); the Junta de Castilla y León (grant LE22A10–2); the Consejería de Salud of the Junta de Andalucía (2009- S0143); the Conselleria de Sanitat of the Generalitat Valenciana (grant AP 061/10); the Recercaixa (grant 2010ACUP 00310); the Regional Government of the Basque Country; the Consejería de Sanidad de la Región de Murcia; European Commission grants FOOD-CT-2006-036224-HIWATE; the Spanish Association Against Cancer (AECC) Scientific Foundation; the Catalan Government DURSI (grant 2014SGR647); the Fundación Caja de Ahorros de Asturias; the University of Oviedo; Societat Catalana de Digestologia; and COST action BM1206 Eucolongene. None of the funders played any role in conducting research or writing the paper.

PURPOSE: Since 2016, the multicase-control study in Spain (MCC-Spain) has focused towards the identification of factors associated with cancer prognosis. Inception cohorts of patients with colorectal, breast and prostate cancers were assembled using the incident cases originally recruited. PARTICIPANTS: 2140 new cases of colorectal cancer, 1732 of breast cancer and 1112 of prostate cancer were initially recruited in 12 Spanish provinces; all cancers were incident and pathologically confirmed. Follow-up was obtained for 2097 (98%), 1685 (97%) and 1055 (94.9%) patients, respectively. FINDINGS TO DATE: Information gathered at recruitment included sociodemographic factors, medical history, lifestyle and environmental exposures. Biological samples were obtained, and 80% of patients were genotyped using a commercial exome array. The follow-up was performed by (1) reviewing medical records; (2) interviewing the patients by phone on quality of life; and (3) verifying vital status and cause of death in the Spanish National Death Index. Ninety-seven per cent of recruited patients were successfully followed up in 2017 or 2018; patient-years of follow-up were 30?914. Most colorectal cancers (52%) were at clinical stage II or lower at recruitment; 819 patients died in the follow-up and the 5-year survival was better for women (74.4%) than men (70.0%). 71% of breast cancers were diagnosed at stages I or II; 206 women with breast cancer died in the follow-up and the 5-year survival was 90.7%. 49% of prostate cancers were diagnosed at stage II and 32% at stage III; 119 patients with prostate cancer died in the follow-up and the 5-year survival was 93.7%. FUTURE PLANS: MCC-Spain has built three prospective cohorts on highly frequent cancers across Spain, allowing to investigate socioeconomic, clinical, lifestyle, environmental and genetic variables as putative prognosis factors determining survival of patients of the three cancers and the inter-relationship of these factors. ; 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, PI18/00181), 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 (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.

A breast-risk score, published in 2016, was developed in white-American women using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors. With the aim of validating the score in the Spanish population, 1,732 breast cancer cases and 1,910 controls were studied. The GRS92, modifiable and non-modifiable risk factor scores were estimated via logistic regression. SNPs without available genotyping were simulated as in the aforementioned 2016 study. The full model score was obtained by combining GRS92, modifiable and non-modifiable risk factor scores. Score performances were tested via the area under the ROC curve (AUROC), net reclassification index (NRI) and integrated discrimination improvement (IDI). Compared with non-modifiable and modifiable factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and 0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved patient classification by 23.6% (NRI?=?0.236), while the modifiable factor score only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study showed the ability of the full model for identifying women at high risk for breast cancer. In conclusion, a model combining genetic and risk factors can be used for stratifying women by their breast cancer risk, which can be applied to individualizing genetic counseling and screening recommendations. ; The study was partially funded by the "Acción Transversal del Cancer" project, approved by the Spanish Council of Ministers on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PI09/00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219), 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 (2009-S0143), 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 European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation and by the Catalan Government DURSI grant 2009SGR1489.

BACKGROUND: Reproductive factors are well known risk factors for breast cancer; however, little is known about how genetic variants in hormonal pathways interact with that relationship. METHODS: One thousand one hundred thirty nine cases of breast cancer in women and 1322 frequency-matched controls were compared. Genetic variants in hormonal pathways (identified in the Kyoto Encyclopedia of Genes and Genomes) were screened according to their relationship with breast cancer using the Cochran-Armitage statistic. Information on reproductive factors was obtained using a face-to-face questionnaire. The interaction among the selected genetic variants and reproductive factors was tested with logistic regression. RESULTS: Concerning C allele in rs2229712, compared to nulliparity in non-carriers the ORs for 1-2 and >?2 deliveries were 0.48 (0.28-0.81) and 0.34 (0.19-0.59), and in C carriers they were 0.92 (0.42-1.98) and 0.71 (0.31-1.61). Similar results were found in women carrying the C allele in rs1269851. Carriers of Allele T in rs35652107 and allele C in rs6018027 had the delivery number effect more pronounced. CONCLUSIONS: The number of deliveries had a dose-response protective effect on breast cancer; women carrying C allele in rs2229712 did not benefit from this protective effect. ; This work was partially funded by the "Accion Transversal del Cancer", approved by the Spanish Ministry Council on the 11th October 2007; The Instituto de Salud Carlos III-FEDER [PI08/1770, PI08/0533, PI08/1359, PI09/ 00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-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]; The Fundación Marqués de Valdecilla [API 10/09]; 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)); The Junta de Castilla y León [LE22A10–2]; The Consejería de Salud of the Junta de Andalucía [2009-S0143]; The Conselleria de Sanitat of the Generalitat Valenciana [AP_061/10]; The Recercaixa [2010ACUP 00310]; The Regional Government of the Basque Country; The Consejería de Sanidad de la Región de Murcia; The European Commission [grants FOOD-CT-2006-036224-HIWATE]; The Spanish Association Against Cancer (AECC) Scientific Foundation; The Catalan Government DURSI [grant 2014SGR647]; The Fundación Caja de Ahorros de Asturias; and the University of Oviedo.

Breast cancer is the most frequent cause of tumors and net survival is increasing. Achieving a higher survival probability reinforces the importance of studying health-related quality of life (HR-QoL). The main aim of this work is to test the relationship between different sociodemographic, clinical and tumor-intrinsic characteristics, and treatment received with HR-QoL measured using SF-12 and the FACT/NCCN (National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy) Breast Symptom Index (FBSI). Women with breast cancer recruited between 2008 and 2013 and followed-up until 2017-2018 in a prospective cohort answered two HR-QoL surveys: the SF-12 and FBSI. The scores obtained were related to woman and tumor characteristics using linear regression models. The telephone survey was answered by 1078 women out of 1685 with medical record follow-up (64%). Increases in all three HR-QoL scores were associated with higher educational level. The score differences between women with university qualifications and women with no schooling were 5.43 for PCS-12, 6.13 for MCS-12 and 4.29 for FBSI. Histological grade at diagnosis and recurrence in the follow-up displayed a significant association with mental and physical HR-QoL, respectively. First-line treatment received was not associated with HR-QoL scores. On the other hand, most tumor characteristics were not associated with HR-QoL. As breast cancer survival is improving, further studies are needed to ascertain if these differences still hold in the long run. ; This study was partially funded by the "Acción Transversal del Cancer", approved on the Spanish Ministry Council on the 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, PI18/00181), 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, 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. Samples: Biological samples were stored at the biobanks supported by Instituto de Salud Carlos III- FEDER: Parc de Salut MAR Biobank (MARBiobanc) (RD09/0076/00036), "Biobanco La Fe" (PT17/0015/0043) and FISABIO Biobank (PT17/0015/0017). Also, at the Public Health Laboratory from Gipuzkoa, the Basque Biobank, the ICOBIOBANC (sponsored by the Catalan Institute of Oncology), the IUOPA Biobank from the University of Oviedo and the ISCIII Biobank. Genotyping: the Spanish "Centro Nacional de Genotipado (CEGEN-ISCIII) provided SNP genotyping services. ; Sí

Phototype has been associated with an increased risk of prostate cancer, and it is yet unknown if it is related to other hormone-dependent cancers, such as breast cancer or whether this association could be considered causal. Methods We examined the association between the phototype and breast and prostate cancers using a Mendelian randomization analysis. We studied 1,738 incident cases of breast cancer and another 817 cases of prostate cancer. To perform a Mendelian randomization analysis on the phototype—cancer relationship, a genetic pigmentation score was required that met the following criteria: (1) the genetic pigmentation score was associated with phototype in controls; (2) the genetic pigmentation score was not associated with confounders in the relationship between phototype and cancer, and (3) the genetic pigmentation score was associated with cancer only through its association with phototype. Once this genetic score is available, the association between genetic pigmentation score and cancer can be identified as the association between phototype and cancer. Results The association between the genetic pigmentation score and phototype in controls showed that a higher genetic pigmentation score was associated with fair skin, blond hair, blue eyes and the presence of freckles. Applying the Mendelian randomization analysis, we verified that there was no association between the genetic pigmentation score and cancers of the breast and prostate. Conclusions Phototype is not associated with breast or prostate cancer. ; This work was partially funded by the ªAccion Transversal del Cáncer", approved by the Spanish Ministry Council on the 11th October 2007; The Instituto de Salud Carlos III-FEDER [PI08/1770, PI08/0533, PI08/1359, PI09/00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-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]; The Fundación Marqués de Valdecilla [API 10/09]; 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)); The Junta de Castilla y León [LE22A10-2]; The Consejería de Salud of the Junta de Andalucía [2009-S0143]; The Conselleria de Sanitat of the Generalitat Valenciana [AP_061/10]; The Recercaixa [2010ACUP 00310]; The Regional Government of the Basque Country; The Consejería de Sanidad de la Región de Murcia; The European Commission [grants FOOD-CT-2006-036224- HIWATE]; The Spanish Association Against Cancer (AECC) Scientific Foundation; The Catalan Government DURSI [grant 2014SGR647]; The Fundación Caja de Ahorros de Asturias; and the University of Oviedo.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used despite their risk of gastrointestinal bleeding or cardiovascular events. We report the profile of people taking NSAIDs in Spain, and we include demographic factors, health-related behaviours and cardiovascular disease history. METHODS: Four thousand sixtyparticipants were selected using a pseudorandom number list from Family Practice lists in 12 Spanish provinces. They completed a face-to-face computerized interview on their NSAID consumption, demographic characteristics, body mass index, alcohol and tobacco consumption and medical history. In addition, participants completed a self-administered food-frequency and alcohol consumption questionnaire. Factors associated with ever and current NSAID consumption were identified by logistic regression. RESULTS: Women consumed more non-aspirin NSAIDs (38.8% [36.7-41.0]) than men (22.3 [20.5-24.2]), but men consumed more aspirin (11.7% [10.3-13.2]) than women (5.2% [4.3-6.3]). Consumption of non-aspirin NSAIDs decrease with age from 44.2% (39.4-49.1) in younger than 45 to 21.1% (18.3-24.2) in older than 75, but the age-pattern for aspirin usage was the opposite. Aspirin was reported by about 11% patients, as being twice as used in men (11.7%) than in women (5.2%); its consumption increased with age from 1.7% (

The St Gallen Conference endorsed in 2013 a series of recommendations on early breast cancer treatment. The main purpose of this article is to ascertain the clinical factors associated with St Gallen-2013 recommendations accomplishment. A cohort of 1152 breast cancer cases diagnosed with pathological stage < 3 in Spain between 2008 and 2013 was begun and then followed-up until 2017/2018. Data on patient and tumour characteristics were obtained from medical records, as well as their first line treatment. First line treatments were classified in three categories, according on whether they included the main St Gallen-2013 recommendations, more than those recommended or less than those recommended. Multinomial logistic regression models were carried out to identify factors associated with this classification and Weibull regression models were used to find out the relationship between this classification and survival. About half of the patients were treated according to St Gallen recommendations; 21% were treated over what was recommended and 33% received less treatment than recommended. Factors associated with treatment over the recommendations were stage II (relative risk ratio [RRR] = 4.2, 2.9-5.9), cancer positive to either progesterone (RRR = 8.1, 4.4-14.9) or oestrogen receptors (RRR = 5.7, 3.0-11.0). Instead, factors associated with lower probability of treatment over the recommendations were age (RRR = 0.7 each 10 years, 0.6-0.8), poor differentiation (RRR = 0.09, 0.04-0.19), HER2 positive (RRR = 0.46, 0.26-0.81) and triple negative cancer (RRR = 0.03, 0.01-0.11). Patients treated less than what was recommended in St Gallen had cancers in stage 0 (RRR = 21.6, 7.2-64.5), poorly differentiated (RRR = 1.9, 1.2-2.9), HER2 positive (RRR = 3.4, 2.4-4.9) and luminal B-like subtype (RRR = 3.6, 2.6-5.1). Women over 65 years old had a higher probability of being treated less than what was recommended if they had luminal B-like, HER2 or triple negative cancer. Treatment over St Gallen was associated with younger women and less severe cancers, while treatment under St Gallen was associated with older women, more severe cancers and cancers expressing HER2 receptors. ; Biological samples were stored at the biobanks supported by Instituto de Salud Carlos III-FEDER: Parc de Salut MAR Biobank (MARBiobanc) (RD09/0076/00036), 'Biobanco La Fe' (RD 09 0076/00021) and FISABIO Biobank (RD09 0076/00058), as well as at the Public Health Laboratory of Gipuzkoa, the Basque Biobank, the ICOBIOBANC (sponsored by the Catalan Institute of Oncology), the IUOPA Biobank of the University of Oviedo, and the ISCIII Biobank. SNP genotyping services were provided by the Spanish 'Centro Nacional de Genotipado' (CEGEN-ISCIII). We thank all the subjects who participated in the study and all MCC-Spain collaborators. This work was supported by the 'Acción Transversal del Cancer', approved by the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III, co-founded by FEDER funds-'a way to build Europe' (Grants PI08/1770, PI08/0533, PI08/1359, PI09/00773, PI09/01286, PI09/01903, PI09/02078, PI09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/00613, and PI15/00069). Support was also provided by the Fundación Marqués de Valdecilla (Grant API 10/09); the Junta de Castilla y León (Grant LE22A10-2); the Consejería de Salud of the Junta de Andalucía (2009-S0143); the Conselleria de Sanitat of the Generalitat Valenciana (Grant AP 061/10); the Recercaixa (Grant 2010ACUP 00310); the Regional Government of the Basque Country; the Consejería de Sanidad de la Región de Murcia; European Commission grants FOOD-CT-2006-036224-HIWATE; the Spanish Association Against Cancer (AECC) Scientific Foundation; the Catalan Government DURSI (Grant 2014SGR647); the Fundación Caja de Ahorros de Asturias; the University of Oviedo; Societat Catalana de Digestologia; and COST action BM1206 Eucolongene. ; Sí

INTRODUCTION: Phototype has been associated with an increased risk of prostate cancer, and it is yet unknown if it is related to other hormone-dependent cancers, such as breast cancer or whether this association could be considered causal. METHODS: We examined the association between the phototype and breast and prostate cancers using a Mendelian randomization analysis. We studied 1,738 incident cases of breast cancer and another 817 cases of prostate cancer. To perform a Mendelian randomization analysis on the phototype-cancer relationship, a genetic pigmentation score was required that met the following criteria: (1) the genetic pigmentation score was associated with phototype in controls; (2) the genetic pigmentation score was not associated with confounders in the relationship between phototype and cancer, and (3) the genetic pigmentation score was associated with cancer only through its association with phototype. Once this genetic score is available, the association between genetic pigmentation score and cancer can be identified as the association between phototype and cancer. RESULTS: The association between the genetic pigmentation score and phototype in controls showed that a higher genetic pigmentation score was associated with fair skin, blond hair, blue eyes and the presence of freckles. Applying the Mendelian randomization analysis, we verified that there was no association between the genetic pigmentation score and cancers of the breast and prostate. CONCLUSIONS: Phototype is not associated with breast or prostate cancer. ; This work was partially funded by the "Accion Transversal del Cancer", approved by the Spanish Ministry Council on the 11th October 2007; The Instituto de Salud Carlos III-FEDER [PI08/1770, PI08/0533, PI08/1359, PI09/00773- Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-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]; The Fundación Marqués de Valdecilla [API 10/09]; 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)); The Junta de Castilla y León [LE22A10-2]; The Consejería de Salud of the Junta de Andalucía [2009-S0143]; The Conselleria de Sanitat of the Generalitat Valenciana [AP_061/10]; The Recercaixa [2010ACUP 00310]; The Regional Government of the Basque Country; The Consejería de Sanidad de la Región de Murcia; The European Commission [grants FOOD-CT-2006-036224- HIWATE]; The Spanish Association Against Cancer (AECC) Scientific Foundation; The Catalan Government DURSI [grant 2014SGR647]; The Fundación Caja de Ahorros de Asturias; and the University of Oviedo.

Background: The objective of our investigation is to study the relationship between the rs4939827 SNP in the SMAD7 gene, Mediterranean diet pattern and the risk of colorectal cancer. Methods: We examined 1087 cases of colorectal cancer and 2409 population controls with available DNA samples from the MCC-Spain study, 2008-2012. Descriptive statistical analyses, and multivariate logistic mixed models were performed. The potential synergistic effect of rs4939827 and the Mediterranean diet pattern was evaluated with logistic regression in different strata of of adherence to the Mediterranean diet and the genotype. Results: High adherence to Mediterrenean diet was statistically significantly associated with colorectal cancer risk. A decreased risk for CRC cancer was observed for the CC compared to the TT genotype (OR = 0.65 and 95% CI = 0.51-0.81) of the rs4939827 SNP Also, we could show an association between the Mediterranean diet pattern (protective factor) and rs4939827. Although the decreased risk for the CC genotype was slightly more pronounced in subjects with high adherence to Mediterrenean diet, there was no statistically significant synergistic effect between genotype CC and adherence to the Mediterranean dietary pattern factors. Conclusion: The SMAD7 gene and specifically the allele C could be protective for colorectal cancer. An independent protective association was also observed between high adherence Mediterranean diet pattern and CRC risk. Findings form this study indicate that high adherence to Mediterranean diet pattern has a protective role for CRC cancer probably involving the Tumor Growth Factor- β pathway in this cancer ; 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, PI09/00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-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), 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 (2009-S0143), 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, by the Catalan Government DURSI grant 2014SGR647, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo

BACKGROUND: The objective of our investigation is to study the relationship between the rs4939827 SNP in the SMAD7 gene, Mediterranean diet pattern and the risk of colorectal cancer. METHODS: We examined 1087 cases of colorectal cancer and 2409 population controls with available DNA samples from the MCC-Spain study, 2008-2012. Descriptive statistical analyses, and multivariate logistic mixed models were performed. The potential synergistic effect of rs4939827 and the Mediterranean diet pattern was evaluated with logistic regression in different strata of of adherence to the Mediterranean diet and the genotype. RESULTS: High adherence to Mediterrenean diet was statistically significantly associated with colorectal cancer risk. A decreased risk for CRC cancer was observed for the CC compared to the TT genotype (OR = 0.65 and 95% CI = 0.51-0.81) of the rs4939827 SNP Also, we could show an association between the Mediterranean diet pattern (protective factor) and rs4939827. Although the decreased risk for the CC genotype was slightly more pronounced in subjects with high adherence to Mediterrenean diet, there was no statistically significant synergistic effect between genotype CC and adherence to the Mediterranean dietary pattern factors. CONCLUSION: The SMAD7 gene and specifically the allele C could be protective for colorectal cancer. An independent protective association was also observed between high adherence Mediterranean diet pattern and CRC risk. Findings form this study indicate that high adherence to Mediterranean diet pattern has a protective role for CRC cancer probably involving the Tumor Growth Factor- β pathway in this cancer. ; 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, PI09/00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-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), 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 (2009-S0143), 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, by the Catalan Government DURSI grant 2014SGR647, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. ; Sí