QRISK3 relation to carotid plaque is higer than that of score in patients with systemic lupus erythematosus.

INTRODUCTION: SLE has been described as an independent risk factor for the development of cardiovascular (CV) disease. Recently, the QRESEARCH risk estimator version 3 (QRISK3) calculator has been launched for CV risk assessment in the general population. QRISK3 now includes the presence of SLE as one of its variables for calculating CV risk. Our objective was to compare the predictive capacity between QRISK3 and the Systematic Coronary Risk Evaluation (SCORE) for the presence of subclinical carotid atherosclerosis in patients with SLE. METHODS: Two hundred and ninety-six patients with SLE were recruited. The presence of subclinical atherosclerosis was evaluated by carotid ultrasound to identify carotid plaque and the thickness of the carotid intima-media (cIMT). QRISK3 and SCORE were calculated. The relationship of QRISK3 and SCORE with each other and with the presence of subclinical carotid atherosclerosis (both carotid plaque and cIMT) was studied. RESULTS: There was no correlation between SCORE and QRISK3 in patients with SLE (Spearman's rho = -0.008, P = 0.90). Although QRISK3 showed a statistically significant correlation with cIMT (Spearman's rho = 0.420, P = 0.000), this relationship was not found between SCORE and cIMT (Spearman's rho = -0.005, P = 0.93). The discrimination capacity of QRISK3 for the presence of carotid plaque was statistically significant and superior to that of SCORE (AUC 0.765 [95% CI: 0.711, 0.820] vs 0.561 [95% CI: 0.494, 0.629], P = 0.000). CONCLUSION: QRISK3 discrimination for subclinical atherosclerosis is higher than that of SCORE. QRISK3, and not SCORE, should be used for the calculation of CV risk in patients with SLE.

A probabilistic model for the prediction of intra-abdominal infection after colorectal surgery.

AIM: Predicting intra-abdominal infections (IAI) after colorectal surgery by means of clinical signs is challenging. A naïve logistic regression modeling approach has some limitations, for which reason we study two potential alternatives: the use of Bayesian networks, and that of logistic regression model. METHODS: Data from patients that had undergone colorectal procedures between 2010 and 2017 were used. The dataset was split into two subsets: (i) that for training the models and (ii) that for testing them. The predictive ability of the models proposed was tested (i) by comparing the ROC curves from days 1 and 3 with all the subjects in the test set and (ii) by studying the evolution of the abovementioned predictive ability from day 1 to day 5. RESULTS: In day 3, the predictive ability of the logistic regression model achieved an AUC of 0.812, 95% CI = (0.746, 0.877), whereas that of the Bayesian network was 0.768, 95% CI = (0.695, 0.840), with a p-value for their comparison of 0.097. The ability of the Bayesian network model to predict IAI does present significant difference in predictive ability from days 3 to 5: AUC(Day 3) = 0.761, 95% CI = (0.680, 0.841) and AUC(Day 5) = 0.837, 95% CI = (0.769, 0.904), with a p-value for their comparison of 0.006. CONCLUSIONS: Whereas at postoperative day 3, a logistic regression model with imputed data should be used to predict IAI; at day 5, when the predictive ability is almost identical, the Bayesian network model should be used.

Fatty acid intake and breast cancer in the Spanish multicase-control study on cancer (MCC-Spain).

PURPOSE: To evaluate the association between dietary fat and fat subtype and breast cancer development. METHODS: We conducted a case-control study with 1181 cases of incident breast cancer, diagnosed between 2007 and 2012, and 1682 population controls frequency matched (by age, sex, and region) from the Spanish multicenter case-control study MCC-Spain. RESULTS: We found a significant protective effect in premenopausal women of total fat intake [OR 0.51 95% CI (0.31-0.86) highest versus lowest tertile], but no effect was observed in menopausal women [OR 1.15 95% CI (0.83-1.60)]. Analyzing by type of fat, this protective effect persisted only for the monounsaturated fatty acids [OR 0.51 95% CI (0.32-0.82)]. In contrast, other fatty acids did not have a significant effect. In addition, a protection against risk of breast cancer was found when polyunsaturated fats were "substituted" by monounsaturated, maintaining the same total fat intake [OR 0.68 95% CI (0.47-0.99)]. Finally, analyzing by breast cancer subtype, we found no effect, except in premenopausal women where intake of moderate [OR 0.52 95% CI (0.33-0.82)] and high monounsaturated fatty acids [OR 0.47 95% CI (0.27-0.82)] maintains a protective effect against ER/PR + tumors. In contrast, in menopausal women, a high intake of monounsaturated fatty acids was associated with higher risk of HER2 + tumors [OR 2.00 95% CI (0.97-4.13)]. CONCLUSION: Our study shows a differential effect of monounsaturated fatty acids according to menopausal status and breast cancer subtype.

Changes in individual and contextual socio-economic level influence on reproductive behavior in Spanish women in the MCC-Spain study.

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.

The RS4939827 polymorphism in the SMAD7 GENE and its association with Mediterranean diet in colorectal carcinogenesis.

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- ß pathway in this cancer.

Relationship between drugs affecting the renin-angiotensin system and colorectal cancer: The MCC-Spain study.

The potential protective effect of renin-angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). To evaluate this association, we conducted a case-control study with 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65years group (OR=0.65 95%CI (0.48-0.89)) and to a lesser degree to men (OR=0.81 95%CI (0.66-0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location.

Evolution of Medical Students' Perception of the Patient's Right to Privacy.

During clinical rotations, medical students experience situations in which the patients' right to privacy may be violated. The aim of this study is to analyze medical students' perception of clinical situations that affect patients' right to privacy, and to look for the influential factors that may contribute to the infringement on their rights, such as the students' age, sex, academic year or parents' educational level. A cross-sectional study was conducted with a survey via "Google Drive". It consisted of 16 questions about personal information, 24 questions about their experience when rotating and 21 questions about their opinion concerning several situations related to the right to privacy. A total of 129 medical students from various Spanish medical schools participated. Only 31% of 3rd-6th year students declared having signed a confidentiality agreement when starting their clinical practice, and most students (52%) reported that doctors "sometimes", "rarely" or "never" introduce themselves and the students when entering the patients' rooms. Additionally, about 50% of all students reported that they would take a picture of a patient's hospitalization report without his/her (consent), which would be useful for an assignment. Important mistakes during medical students' rotations have been observed, as well as a general lack of knowledge regarding patient's right to privacy among Spanish medical students. Men and older students showed better knowledge of current legislation, as well as those whose parents were both university-educated and those in higher academic years.

Evaluation of Feature Selection Techniques for Breast Cancer Risk Prediction.

This study evaluates several feature ranking techniques together with some classifiers based on machine learning to identify relevant factors regarding the probability of contracting breast cancer and improve the performance of risk prediction models for breast cancer in a healthy population. The dataset with 919 cases and 946 controls comes from the MCC-Spain study and includes only environmental and genetic features. Breast cancer is a major public health problem. Our aim is to analyze which factors in the cancer risk prediction model are the most important for breast cancer prediction. Likewise, quantifying the stability of feature selection methods becomes essential before trying to gain insight into the data. This paper assesses several feature selection algorithms in terms of performance for a set of predictive models. Furthermore, their robustness is quantified to analyze both the similarity between the feature selection rankings and their own stability. The ranking provided by the SVM-RFE approach leads to the best performance in terms of the area under the ROC curve (AUC) metric. Top-47 ranked features obtained with this approach fed to the Logistic Regression classifier achieve an AUC = 0.616. This means an improvement of 5.8% in comparison with the full feature set. Furthermore, the SVM-RFE ranking technique turned out to be highly stable (as well as Random Forest), whereas relief and the wrapper approaches are quite unstable. This study demonstrates that the stability and performance of the model should be studied together as Random Forest and SVM-RFE turned out to be the most stable algorithms, but in terms of model performance SVM-RFE outperforms Random Forest.

QRISK3 Performance in the Assessment of Cardiovascular Risk in Patients with Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) has been described as an independent risk factor for the development of cardiovascular (CV) disease. Since the QRESEARCH risk estimator version 3 (QRISK3) calculator was recently proposed to assess CV in the general population, our objective was to compare the predictive ability of QRISK3 with that of a well-established European CV risk calculator, the Systematic Coronary Risk Assessment (SCORE), to identify the presence of subclinical carotid atherosclerosis in patients with IBD. In all, 186 patients with IBD and 178 controls were recruited. The presence of subclinical atherosclerosis was evaluated by carotid ultrasound to identify carotid plaque and the thickness of the carotid intima-media (cIMT). QRISK3 and SCORE were calculated. The relationship of QRISK3 and SCORE with each other and with the presence of subclinical carotid atherosclerosis (both carotid plaque and cIMT) was studied in patients and controls. SCORE (0.2 (interquartile range 0.1-0.9) vs. 0.4 (0.1-1.4), p = 0.55) and QRISK3 1.7 ((0.6-4.6) vs. 3.0 (1.0-7.8), p = 0.16) absolute values did not differ between patients and controls. QRISK3 and SCORE correlated equally with cIMT within both populations. However, SCORE correlation with cIMT was found to be significantly lower in patients with IBD when compared to controls (Spearman's Rho 0.715 vs. 0.587, p = 0.034). Discrimination analysis of both calculators with carotid plaque was similar within both populations. Nevertheless, in patients with IBD, QRISK3 showed a trend toward a higher discrimination (QRISK3 area under the curve 0.812 (95%CI 0.748-0.875) vs. SCORE 0.790 (95%CI 0.723-0.856), p = 0.051). In conclusion, QRISK3 discrimination for subclinical atherosclerosis is optimal and equivalent to that of SCORE in IBD patients. However, our findings highlight the role of QRISK3 as an appropriate tool for the assessment of CV risk in patients with IBD.

Author Correction: Validating a breast cancer score in Spanish women. The MCC-Spain study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause.

Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72-1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95-1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81-1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84-1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70-1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66-0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.

Vitamin D exposure and Risk of Breast Cancer: a meta-analysis.

The relationship between vitamin D and breast cancer is still controversial. The present meta-analysis examines the effects of the 25(OH)D, 1,25(OH)2D and vitamin D intake on breast cancer risk. For this purpose, a PubMed, Scopus and Web of Science-databases search was conducted including all papers published with the keywords "breast cancer" and "vitamin D" with at least one reported relative risk (RR) or odds ratio (OR). In total sixty eight studies published between 1998 and 2018 were analyzed. Information about type of study, hormonal receptors and menopausal status was retrieved. Pooled OR or RR were estimated by weighting individual OR/RR by the inverse of their variance Our study showed a protective effect between 25 (OH) D and breast cancer in both cohort studies (RR = 0.85, 95%CI:0.74-0.98) and case-control studies (OR = 0.65, 95%CI: 0.56-0.76). However, analyzing by menopausal status, the protective vitamin D - breast cancer association persisted only in the premenopausal group (OR = 0.67, 95%CI: 0.49-0.92) when restricting the analysis to nested case-control studies. No significant association was found for vitamin D intake or 1,25(OH)2D. CONCLUSION: This systematic review suggests a protective relationship between circulating vitamin D (measured as 25(OH) D) and breast cancer development in premenopausal women.

Pigmentation phototype and prostate and breast cancer in a select Spanish population-A Mendelian randomization analysis in the MCC-Spain study.

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.

Validating a breast cancer score in Spanish women. The MCC-Spain study.

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.

Risk Model for Prostate Cancer Using Environmental and Genetic Factors in the Spanish Multi-Case-Control (MCC) Study.

Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model.

Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study.

Colorectal cancer (CRC) screening of the average risk population is only indicated according to age. We aim to elaborate a model to stratify the risk of CRC by incorporating environmental data and single nucleotide polymorphisms (SNP). The MCC-Spain case-control study included 1336 CRC cases and 2744 controls. Subjects were interviewed on lifestyle factors, family and medical history. Twenty-one CRC susceptibility SNPs were genotyped. The environmental risk model, which included alcohol consumption, obesity, physical activity, red meat and vegetable consumption, and nonsteroidal anti-inflammatory drug use, contributed to CRC with an average per factor OR of 1.36 (95% CI 1.27 to 1.45). Family history of CRC contributed an OR of 2.25 (95% CI 1.87 to 2.72), and each additional SNP contributed an OR of 1.07 (95% CI 1.04 to 1.10). The risk of subjects with more than 25 risk alleles (5th quintile) was 82% higher (OR 1.82, 95% CI 1.11 to 2.98) than subjects with less than 19 alleles (1st quintile). This risk model, with an AUROC curve of 0.63 (95% CI 0.60 to 0.66), could be useful to stratify individuals. Environmental factors had more weight than the genetic score, which should be considered to encourage patients to achieve a healthier lifestyle.

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).