Suchergebnisse

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.

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. ; This research was funded 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 and COST action BM1206 Eucolongene.

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.