Tumour characteristics and survivorship in a cohort of breast cancer: the MCC-Spain study.

PURPOSE: The objective of this study is to analyse the relative survival with breast cancer in women diagnosed after new treatments were generalised and to ascertain the current effect that tumour characteristics such as grade, stage or subtype have on survival as well as the new AJCC-pathological prognostic score. METHODS: The breast cancer MCC-Spain follow-up study is a prospective cohort study of 1685 incident breast cancer cases. Women between 20 and 85 years old were recruited between the years 2008 and 2013 in 18 hospitals located in 10 Spanish provinces and they have been followed until 2017/2018. Relative survival was estimated after 3, 5 and 8 years of follow-up using Ederer II method. In addition, Weibull regression adjusted by age, hospital, grade and stage was used to investigate prognosis factors. RESULTS: Among components of TNM staging system, tumour size greater than 50 mm (i.e. T3 or T4) more than doubled the risk of dying, while N3 nodal involvement and presence of metastasis had a huge effect on mortality. The AJCC pathological prognostic score strongly correlated with survival; thus, hazard ratios increased as the score rose, being 2.31, 4.00, 4.94, 7.92, 2.26, 14.9 and 58.9 for scores IB, IIA, IIB, IIIA, IIIB, IIIC and IV, respectively. CONCLUSION: Both TNM staging and histological/molecular biomarkers are associated with overall survival in Spanish women with breast cancer; when both are combined in the AJCC pathological prognosis score, the prognostic value improved with risk indices that increased rapidly as the pathological prognosis score increased.

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.

Domain-specific patterns of physical activity and risk of breast cancer sub-types in the MCC-Spain study.

PURPOSE: Literature on the separate effects of physical activities (PA) on risk of breast cancer (BC) sub-types is heterogeneous. We investigated domain-specific associations between PA and BC risk by menopausal status and molecular subtype. METHODS: 1389 histologically confirmed invasive BC cases and 1712 controls from the MCC-Spain study were included (age: 20-85 years). Questionnaire information on PA at work, at home, and during leisure time, including recreational PA and sedentary time, and data on reproductive history, anthropometry, family history of BC, diet, and lifestyles were obtained through face-to-face interviews. Information on the expression of oestrogen (ER), progesterone (PR), and HER2 receptors was available for > 95% of the cases. Mixed-effects multivariable logistic regression models were used to estimate odds ratios (OR) of BC sub-types. RESULTS: Occupational PA (OPA) intensity was associated with higher BC risk. Associations were stronger for pre-menopausal (ORactive/very active vs. sedentary job 1.89; 95% confidence interval (CI) 1.22, 2.91) and ER+/PR+, HER2- tumours (OR 1.80; 95% CI 1.28, 2.53). Sedentary time was associated with higher risk of post-menopausal BC (OR6-9 vs. <3 h/day 1.69; 95% CI 1.22, 2.32). Moderate-to-high-intensity household (HPA) and recreational PA (RPA) were inversely associated with BC occurrence in pre- and post-menopausal women, with estimated 14-33% lower risks (P for trend < 0.001) above 1000 MET·min/week. CONCLUSIONS: Higher levels of HPA and RPA were associated with lower risk of BC, with heterogeneity by molecular type, whereas sitting time was a consistent independent risk factor of BC risk. The positive association found for OPA with ER+/PR+ BC deserves further investigation.

[Family history of first degree as a risk factor for colorectal cancer]. / Antecedentes familiares de primer grado como factor de riesgo en el cáncer colorrectal.

OBJECTIVE: To evaluate the association between first-degree family history and colorectal cancer (CRC). METHOD: We analyzed data from 2857 controls and 1360 CRC cases, collected in the MCC-Spain project. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) of association with the family history of CRC was estimated by non-conditional logistic regression. RESULTS: First-degree relatives doubled the risk of CRC (OR: 2.19; 95% CI: 1.80-2.66), increasing in those with two or more (OR: 4.22; 95% CI: 2.29-7.78) and in those whose relatives were diagnosed before 50 years (OR: 3.24; 95% CI: 1.52-6.91). Regarding the association of the family history with the location, no significant differences were observed between colon and rectum, but there were in the relation of these with the age of diagnosis, having more relatives those diagnosed before 50 years (OR: 4.79; 95% CI: 2.65-8.65). CONCLUSIONS: First-degree relatives of CRC increase the chances of developing this tumor, they also increase when the relative is diagnosed at an early age. Therefore, it must be a target population on which to carry out prevention measures.

Risk of gastric cancer in the environs of industrial facilities in the MCC-Spain study.

BACKGROUND: Gastric cancer is the fifth most frequent tumor worldwide. In Spain, it presents a large geographic variability in incidence, suggesting a possible role of environmental factors in its etiology. Therefore, epidemiologic research focused on environmental exposures is necessary. OBJECTIVES: To assess the association between risk of gastric cancer (by histological type and tumor site) and residential proximity to industrial installations, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer conducted in Spain (MCC-Spain). METHODS: In this study, 2664 controls and 137 gastric cancer cases from 9 provinces, frequency matched by province of residence, age, and sex were included. Distances from the individuals' residences to the 106 industries located in the study areas were computed. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industries, adjusting for matching variables and potential confounders. RESULTS: Overall, no excess risk of gastric cancer was observed in people living close to the industrial installations, with ORs ranging from 0.73 (at ≤2.5 km) to 0.93 (at ≤1.5 km). However, by industrial sector, excess risks (OR; 95%CI) were found near organic chemical industry (3.51; 1.42-8.69 at ≤2 km), inorganic chemical industry (3.33; 1.12-9.85 at ≤2 km), food/beverage sector (2.48; 1.12-5.50 at ≤2 km), and surface treatment using organic solvents (3.59; 1.40-9.22 at ≤3 km). By specific pollutant, a statistically significant excess risk (OR; 95%CI) was found near (≤3 km) industries releasing nonylphenol (6.43; 2.30-17.97) and antimony (4.82; 1.94-12.01). CONCLUSIONS: The results suggest no association between risk of gastric cancer and living in the proximity to the industrial facilities as a whole. However, a few associations were detected near some industrial sectors and installations releasing specific pollutants.

Association between Polyphenol Intake and Gastric Cancer Risk by Anatomic and Histologic Subtypes: MCC-Spain.

Several anticancer properties have been largely attributed to phenolics in in vivo and in vitro studies, but epidemiologic evidence is still scarce. Furthermore, some classes have not been studied in relation to gastric cancer (GC). The aim of this study was to assess the relationship between the intake of phenolic acids, stilbenes, and other phenolics and the risk of developing GC and its anatomical and histological subtypes. We used data from a multi-case-control study (MCC-Spain) obtained from different regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed effects logistic regression considering quartiles of phenolic intake. Our results showed an inverse association between stilbene and lignan intake and GC risk (ORQ4 vs. Q1 = 0.47; 95% CI: 0.32-0.69 and ORQ4 vs. Q1 = 0.53; 95% CI: 0.36-0.77, respectively). We found no overall association between total phenolic acid and other polyphenol class intake and GC risk. However, hydroxybenzaldehydes (ORQ4 vs. Q1 = 0.41; 95% CI: 0.28-0.61), hydroxycoumarins (ORQ4 vs. Q1 = 0.49; 95% CI: 0.34-0.71), and tyrosols (ORQ4 vs. Q1 = 0.56; 95% CI: 0.39-0.80) were inversely associated with GC risk. No differences were found in the analysis by anatomical or histological subtypes. In conclusion, a diet high in stilbenes, lignans, hydroxybenzaldehydes, hydroxycoumarins, and tyrosols was associated with a lower GC risk. Further prospective studies are needed to confirm our results.

Residential proximity to industrial pollution sources and colorectal cancer risk: A multicase-control study (MCC-Spain).

BACKGROUND: Colorectal cancer is the third most frequent tumor in males and the second in females worldwide. In Spain, it is an important and growing health problem, and epidemiologic research focused on potential risk factors, such as environmental exposures, is necessary. OBJECTIVES: To analyze the association between colorectal cancer risk and residential proximity to industries, according to pollution discharge route, industrial groups, categories of carcinogens and other toxic substances, and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). METHODS: MCC-Spain included 557 colorectal cancer cases and 2948 controls in 11 provinces, frequency matched by sex, age, and region of residence. Distances were computed from subjects' residences to each of the 134 industries located in the study area. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industrial facilities, adjusting for matching variables and other confounders. RESULTS: Excess risk (OR; 95%CI) of colorectal cancer was detected near industries overall for all distances analyzed, from 1 km (2.03; 1.44-2.87) to 3 km (1.26; 1.00-1.59). In general, industries releasing pollutants to air showed higher excess risks than facilities releasing pollution to water. By industrial sector, excess risk (OR; 95%CI) was found near (≤3 km) production of metals (2.66; 1.77-4.00), surface treatment of metals (1.48; 1.08-2.02), glass and mineral fibers (2.06; 1.39-3.07), organic chemical industry (4.80; 3.20-7.20), inorganic chemical industry (6.74; 4.38-10.36), food/beverage sector (3.34; 2.38-4.68), and surface treatment using organic solvents (6.16; 4.06-9.36). By pollutants, the main excess risks (OR; 95%CI) were found near (≤3 km) industries releasing nonylphenol (9.19; 5.91-14.28), antimony (5.30; 3.45-8.15), naphthalene (3.11; 2.16-4.49), organotin compounds (2.64; 1.76-3.98), manganese (2.53; 1.63-3.93), dichloromethane (2.52; 1.74-3.66), and vanadium (2.49; 1.59-3.91). CONCLUSIONS: Our results support the hypothesis that residing in the proximity of industries may be a risk factor for colorectal cancer.

Validation of self-reported perception of proximity to industrial facilities: MCC-Spain study.

BACKGROUND: Self-reported data about environmental exposures can lead to measurement error. OBJECTIVES: To validate the self-reported perception of proximity to industrial facilities. METHODS: MCC-Spain is a population-based multicase-control study of cancer in Spain that recruited incident cases of breast, colorectal, prostate, and stomach cancer. The participant's current residence and the location of the industries were geocoded, and the linear distance between them was calculated (gold standard). The epidemiological questionnaire included a question to determine whether the participants perceived the presence of any industry at ≤1 km from their residences. Sensitivity and specificity of individuals' perception of proximity to industries were estimated as measures of classification accuracy, and the area under the curve (AUC) and adjusted odds ratios (aORs) of misclassification were calculated as measures of discrimination. Analyses were performed for all cases and controls, and by tumor location, educational level, sex, industrial sector, and length of residence. Finally, aORs of cancer associated with real and self-reported distances were calculated to explore differences in the estimation of risk between these measures. RESULTS: Sensitivity of the questionnaire was limited (0.48) whereas specificity was excellent (0.89). AUC was sufficient (0.68). Participants with breast (aOR(95%CI) = 2.03 (1.67;2.46)), colorectal (aOR(95%CI) = 1.41 (1.20;1.64)) and stomach (aOR(95%CI) = 1.59 (1.20;2.10)) cancer showed higher risk of misclassification than controls. This risk was higher for lower educational levels (aOR15 years (95%CI) = 0.56 (0.36;0.85)). The use of self-reported proximity vs. real distance to industrial facilities biased the effect on cancer risk towards the nullity. CONCLUSIONS: Self-reported distance to industrial facilities can be a useful tool for hypothesis generation, but hypothesis-testing studies should use real distance to report valid conclusions. The sensitivity of the question might be improved with a more specific formulation.

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 effects 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.

Compositional analysis of dietary patterns.

Instead of looking at individual nutrients or foods, dietary pattern analysis has emerged as a promising approach to examine the relationship between diet and health outcomes. Despite dietary patterns being compositional (i.e. usually a higher intake of some foods implies that less of other foods are being consumed), compositional data analysis has not yet been applied in this setting. We describe three compositional data analysis approaches (compositional principal component analysis, balances and principal balances) that enable the extraction of dietary patterns by using control subjects from the Spanish multicase-control (MCC-Spain) study. In particular, principal balances overcome the limitations of purely data-driven or investigator-driven methods and present dietary patterns as trade-offs between eating more of some foods and less of others.

Cohort profile: the MCC-Spain follow-up on colorectal, breast and prostate cancers: study design and initial results.

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.

Dietary Inflammatory Index, Dietary Non-Enzymatic Antioxidant Capacity, and Colorectal and Breast Cancer Risk (MCC-Spain Study).

Inflammation and antioxidant capacity have been associated with colorectal and breast cancer. We computed the dietary inflammatory index (DII®), and the total dietary non-enzymatic antioxidant capacity (NEAC) and associated them with colorectal and breast cancer risk in the population-based multi case-control study in Spain (MCC-Spain). We included 1852 colorectal cancer and 1567 breast cancer cases, and 3447 and 1486 population controls, respectively. DII score and NEAC were derived using data from a semi-quantitative validated food frequency questionnaire. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for energy-adjusted DII (E-DII), and a score combining E-DII and NEAC. E-DII was associated with colorectal cancer risk (OR = 1.93, highest quartile versus lowest, 95%CI:1.60-2.32; p-trend: <0.001); this increase was observed for both colon and rectal cancer. Less pronounced increased risks were observed for breast cancer (OR = 1.22, highest quartile versus lowest, 95%CI:0.99-1.52, p-trend: >0.10). The combined score of high E-DII scores and low antioxidant values were associated with colorectal cancer risk (OR = 1.48, highest quartile versus lowest, 95%CI: 1.26-1.74; p-trend: <0.001), but not breast cancer. This study provides evidence that a pro-inflammatory diet is associated with increased colorectal cancer risk while findings for breast cancer were less consistent.

The Dietary Inflammatory Index and Chronic Lymphocytic Leukaemia in the MCC Spain Study.

Chronic inflammation plays a role in the development of chronic lymphocytic leukaemia (CLL), and diet might modulate chronic inflammation. This study aims to evaluate the association between the dietary inflammatory index (DII®) and CLL. A total of 366 CLL cases and 1643 controls of the Spanish multicase-control (MCC) Spain study were included. The inflammatory potential of the diet was assessed using the energy-adjusted dietary inflammatory index (E-DII) based on 30 items from a validated semi-quantitative food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models controlling for potential confounders. Overall, a modest, non-statistically significant, positive association was observed between CLL and E-DII scores (OR for a one-unit increase in E-DII: 1.05 (CI 95%: 0.99, 1.12), p-value = 0.09 and by tertiles: ORT2vsT1: 1.20 (CI 95%: 0.90, 1.59); OR T3vsT1: 1.21 (CI 95%: 0.90, 1.62), p trend = 0.21). These results were independent from disease severity (p-het: 0.70), time from diagnosis (p-het: 0.67) and CLL treatment received (p-het: 0.56). No interactions were detected. In conclusion, the consumption of a diet with high pro-inflammatory components was not significantly associated with CLL. Changes towards a more pro-inflammatory dietary pattern in younger generations not included here warrant future research.

Chemical quality of tap water in Madrid: multicase control cancer study in Spain (MCC-Spain).

Chronic consumption of water, which contains contaminants, may give rise to adverse health effects. The Madrid region, covered by the population-based multicase-control (MCC-Spain) study, includes two drinking water supply areas. The different sources of the water, coupled together with the possible differences in water management, mean that there may be differences in drinking water quality. In the context of the MCC study, our aims were to describe contaminant concentrations in tap water drawn from various sampling points distributed around the region, assess these concentrations by reference to guideline values and study possible differences between the two supply areas. Tap water samples were collected from 34 sampling points in 7 towns in the Madrid region (19-29 April 2010), and 23 contaminants (metals, nitrates, disinfection by-product and Mutagen X levels) were quantified. We undertook a descriptive analysis of the contaminant concentrations in the water and compared them between the two water supply areas (Wilcoxon test). We created maps representing the distribution of the concentrations observed at water sampling points and assessed the correlations (Spearman's coefficient) between the different parameters measured. The concentrations of the contaminants were below guideline values. There were differences between the two supply areas in concentration of nitrates (p value = 0.0051) and certain disinfection by-products. While there were positive correlations (rho >0.70) among some disinfection by-products, no correlations were found in metals or nitrates. The differences in nitrate levels could be linked to differences in farming/industrial activities in the catchment areas and in disinfection by-products might be related to the existence of different treatment systems or bromine content in source waters.

Antecedentes familiares de primer grado como factor de riesgo en el cáncer colorrectal / Family history of first degree as a risk factor for colorectal cancer

Objetivo: El objetivo de este estudio es evaluar la asociación entre antecedentes familiares (AF) de primer grado y cáncer colorrectal (CCR). Método: Se incluyeron 2857 controles y 1360 casos de CCR, del estudio MCC-Spain. La odds ratio (OR) y el intervalo de confianza del 95% (IC95%) de los AF de primer grado y el CCR se estimaron mediante regresión logística no condicional según la localización tumoral en los casos. Resultados: Los AF de primer grado duplicaron el riesgo de CCR (OR: 2,19;IC95%: 1,80-2,66), incrementándose en aquellos que presentaban dos o más (OR: 4,22; IC95%: 2,29-7,78) y en aquellos cuyos familiares fueron diagnosticados antes de los 50 anos ˜ (OR: 3,24; IC95%: 1,52-6,91). Presentar AF se relacionó con estilos de vida como un menor consumo de vegetales. En cuanto a la asociación de los AF con la localización no se observaron diferencias significativas entre colon y recto, pero sí en la relación de estas con la edad de diagnóstico, presentando más AF los diagnosticados antes de los 50 anos ˜ (OR: 4,79; IC95%:2,65-8,65).. Conclusiones: Presentar AF de primer grado de CCR aumenta las probabilidades de desarrollar este cáncer, y también se elevan cuando el familiar es diagnosticado a edad temprana. Por ello, debe ser una población diana sobre la que incrementar las medidas de prevención. (AU)

Objective: To evaluate the association between first-degree family history and colorectal cancer (CRC). Method: We analyzed data from 2857 controls and 1360 CRC cases, collected in the MCC-Spain project. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) of association with the family history of CRC was estimated by non-conditional logistic regression. Results: First-degree relatives doubled the risk of CRC (OR: 2.19; 95% CI: 1.80–2.66), increasing in those with two or more (OR: 4.22; 95% CI: 2.29–7.78) and in those whose relatives were diagnosed before 50 years (OR: 3.24; 95% CI: 1.52–6.91). Regarding the association of the family history with the location, no significant differences were observed between colon and rectum, but there were in the relation of these with the age of diagnosis, having more relatives those diagnosed before 50 years (OR: 4.79; 95% CI:2.65–8.65). Conclusions: First-degree relatives of CRC increase the chances of developing this tumor,they also increase when the relative is diagnosed at an early age. Therefore, it must be a target population on which to carry out prevention measures. (AU)

Perinatal and childhood factors and risk of prostate cancer in adulthood: MCC-Spain case-control study.

BACKGROUND: In utero and early-life exposures are suspected to modulate the risk of prostate cancer. This study examines the influence of certain perinatal and childhood-related factors on prostate cancer risk overall and by Gleason score at biopsy. METHODS: MCC-Spain is a multicase-control study where 1088 histologically-confirmed incident prostate cancer cases (aged 42-85years) and 1345 population-based controls (aged 38-85years), frequency matched by age and province of recruitment, were recruited in 7 Spanish provinces. Self-reported perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with prostate cancer risk, globally and according to Gleason score at biopsy, was evaluated using logistic and multinomial regression mixed models, adjusting for age, family history of prostate cancer, educational level and body mass index one year before the interview, and including the province as a random effect term. RESULTS: Most perinatal factors were not related to prostate cancer risk, with the exception of middle-high socioeconomic level at birth (OR for high grade tumors=1.36; 95%CI=1.09-1.68). Regarding puberty, risk rose by 6% for each year of delayed onset (OR=1.06; 95%CI=1.01-1.10; p trend=0.016), with a clear excess of risk in men who reached puberty after age 15 (OR:1.35; 95%CI=1.08-1.68). A borderline significant positive association with prepubertal height was also observed (p trend=0.094). CONCLUSION: Some exposures experienced in utero and during adolescence, when the prostate is still maturing, might be relevant for prostate cancer risk in adulthood.