Effect of time of day of recreational and household physical activity on prostate and breast cancer risk (MCC-Spain study).

Experimental evidence indicates that exercise performed at different times of the day may affect circadian rhythms and circadian disruption has been linked to breast and prostate cancer. We examined in a population-based case-control study (MCC-Spain) if the time-of-day when physical activity is done affects prostate and breast cancer risk. Lifetime recreational and household physical activity was assessed by in-person interviews. Information on time-of-day of activity (assessed approximately 3 years after the assessment of lifetime physical activity and confounders) was available for 781 breast cancer cases, 865 population female controls, 504 prostate cases and 645 population male controls from 10 Spanish regions, 2008-2013. We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for different activity timings compared to inactive subjects using unconditional logistic regression adjusting for confounders. Early morning (8-10 am) activity was associated with a protective effect compared to no physical activity for both breast (OR = 0.74, 95% CI = 0.48-1.15) and prostate cancer (OR = 0.73, 95% CI = 0.44-1.20); meta-OR for the two cancers combined 0.74 (95%CI = 0.53-1.02). There was no effect observed for breast or prostate cancer for late morning to afternoon activity while a protective effect was also observed for evening activity only for prostate cancer (OR = 0.75, 95% CI = 0.45-1.24). Protective effects of early morning activity were more pronounced for intermediate/evening chronotypes for both cancers. This is the first population-based investigation identifying a differential effect of timing of physical activity on cancer risk with more pronounced effects for morning hour activity. Our results, if confirmed, may improve current physical activity recommendations for cancer prevention.

Low-grade screen-detected ductal carcinoma in situ progresses more slowly than high-grade lesions: evidence from an international multi-centre study.

PURPOSE: Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening. METHODS: We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment. RESULTS: Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50-69 years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4-31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p < 0.001). CONCLUSIONS: These results suggest that the duration of the preclinical detectable phase is longer for low than for high-grade DCIS. The findings from this large multi-centre, international study emphasize that the management of low-grade DCIS should be carefully scrutinized in order to minimize overtreatment of screen-detected slow-growing or indolent lesions. The high variation by site in the proportion of low grade suggests that further pathology standardization and training would be beneficial.

Occupation and mammographic density: A population-based study (DDM-Occup).

INTRODUCTION: High mammographic density is one of the main risk factors for breast cancer. Although several occupations have been associated with breast cancer, there are no previous occupational studies exploring the association with mammographic density. Our objective was to identify occupations associated with high mammographic density in Spanish female workers. METHODS: We conducted a population-based cross-sectional study of occupational determinants of high mammographic density in Spain, based on 1476 women, aged 45-68 years, recruited from seven screening centers within the Spanish Breast Cancer Screening Program network. Reproductive, family, personal, and occupational history data were collected. The latest occupation of each woman was collected and coded according to the 1994 National Classification of Occupations. Mammographic density was assessed from the cranio-caudal mammogram of the left breast using a semi-automated computer-assisted tool. Association between mammographic density and occupation was evaluated by using mixed linear regression models, using log-transformed percentage of mammographic density as dependent variable. Models were adjusted for age, body mass index, menopausal status, parity, smoking, alcohol intake, educational level, type of mammography, first-degree relative with breast cancer, and hormonal replacement therapy use. Screening center and professional reader were included as random effects terms. RESULTS: Mammographic density was higher, although non-statistically significant, among secondary school teachers (eß = 1.41; 95%CI = 0.98-2.03) and nurses (eß = 1.23; 95%CI = 0.96-1.59), whereas workers engaged in the care of people (eß = 0.81; 95%CI = 0.66-1.00) and housewives (eß = 0.87; 95%CI = 0.79-0.95) showed an inverse association with mammographic density. A positive trend for every 5 years working as secondary school teachers was also detected (p-value = 0.035). CONCLUSIONS: Nurses and secondary school teachers were the occupations with the highest mammographic density in our study, showing the latter a positive trend with duration of employment. Future studies are necessary to confirm if these results are due to chance or are the result of a true association whose causal hypothesis is, for the moment, unknown.

Calorie intake, olive oil consumption and mammographic density among Spanish women.

High mammographic density (MD) is one of the main risk factors for development of breast cancer. To date, however, relatively few studies have evaluated the association between MD and diet. In this cross-sectional study, we assessed the association between MD (measured using Boyd's semiquantitative scale with five categories: <10%, 10-25%, 25-50%, 50-75% and >75%) and diet (measured using a food frequency questionnaire validated in a Spanish population) among 3,548 peri- and postmenopausal women drawn from seven breast cancer screening programs in Spain. Multivariate ordinal logistic regression models, adjusted for age, body mass index (BMI), energy intake and protein consumption as well as other confounders, showed an association between greater calorie intake and greater MD [odds ratio (OR) = 1.23; 95% confidence interval (CI) = 1.10-1.38, for every increase of 500 cal/day], yet high consumption of olive oil was nevertheless found to reduce the prevalence of high MD (OR = 0.86;95% CI = 0.76-0.96, for every increase of 22 g/day in olive oil consumption); and, while greater intake of whole milk was likewise associated with higher MD (OR = 1.10; 95%CI 1.00-1.20, for every increase of 200 g/day), higher consumption of protein (OR = 0.89; 95% CI 0.80-1.00, for every increase of 30 g/day) and white meat (p for trend 0.041) was found to be inversely associated with MD. Our study, the largest to date to assess the association between diet and MD, suggests that MD is associated with modifiable dietary factors, such as calorie intake and olive oil consumption. These foods could thus modulate the prevalence of high MD, and important risk marker for breast cancer.

Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study.

INTRODUCTION: It is not clear whether high mammographic density (MD) is equally associated with all subtypes of breast cancer (BC). We investigated the association between MD and subsequent BC, considering invasiveness, means of detection, pathologic subtype, and the time elapsed since mammographic exploration and BC diagnosis. METHODS: BC cases occurring in the population of women who attended screening from 1997 through 2004 in Navarre, a Spanish region with a fully consolidated screening program, were identified via record linkage with the Navarre Cancer Registry (n = 1,172). Information was extracted from the records of their first attendance at screening in that period. For each case, we randomly selected four controls, matched by screening round, year of birth, and place of residence. Cases were classified according to invasiveness (ductal carcinoma in situ (DCIS) versus invasive tumors), pathologic subtype (considering hormonal receptors and HER2), and type of diagnosis (screen-detected versus interval cases). MD was evaluated by a single, experienced radiologist by using a semiquantitative scale. Data on BC risk factors were obtained by the screening program in the corresponding round. The association between MD and tumor subtype was assessed by using conditional logistic regression. RESULTS: MD was clearly associated with subsequent BC. The odds ratio (OR) for the highest MD category (MD >75%) compared with the reference category (MD <10%) was similar for DCIS (OR = 3.47; 95% CI = 1.46 to 8.27) and invasive tumors (OR = 2.95; 95% CI = 2.01 to 4.35). The excess risk was particularly high for interval cases (OR = 7.72; 95% CI = 4.02 to 14.81) in comparison with screened detected tumors (OR = 2.17; 95% CI = 1.40 to 3.36). Sensitivity analyses excluding interval cases diagnosed in the first year after MD assessment or immediately after an early recall to screening yielded similar results. No differences were seen regarding pathologic subtypes. The excess risk associated with MD persisted for at least 7 to 8 years after mammographic exploration. CONCLUSIONS: Our results confirm that MD is an important risk factor for all types of breast cancer. High breast density strongly increases the risk of developing an interval tumor, and this excess risk is not completely explained by a possible masking effect.

Recalibration of the Gail model for predicting invasive breast cancer risk in Spanish women: a population-based cohort study.

The Gail model for predicting the absolute risk of invasive breast cancer has been validated extensively in US populations, but its performance in the international setting remains uncertain. We evaluated the predictive accuracy of the Gail model in 54,649 Spanish women aged 45-68 years who were free of breast cancer at the 1996-1998 baseline mammographic examination in the population-based Navarre Breast Cancer Screening Program. Incident cases of invasive breast cancer and competing deaths were ascertained until the end of 2005 (average follow-up of 7.7 years) through linkage with population-based cancer and mortality registries. The Gail model was tested for calibration and discrimination in its original form and after recalibration to the lower breast cancer incidence and risk factor prevalence in the study cohort, and compared through cross-validation with a Navarre model fully developed from this cohort. The original Gail model overpredicted significantly the 835 cases of invasive breast cancer observed in the cohort (ratio of expected to observed cases 1.46, 95 % CI 1.36-1.56). The recalibrated Gail model was well calibrated overall (expected-to-observed ratio 1.00, 95 % CI 0.94-1.07), but it tended to underestimate risk for women in low-risk quintiles and to overestimate risk in high-risk quintiles (P = 0.01). The Navarre model showed good cross-validated calibration overall (expected-to-observed ratio 0.98, 95 % CI 0.92-1.05) and in different cohort subsets. The Navarre and Gail models had modest cross-validated discrimination indexes of 0.542 (95 % CI 0.521-0.564) and 0.544 (95 % CI 0.523-0.565), respectively. Although the original Gail model cannot be applied directly to populations with different underlying rates of invasive breast cancer, it can readily be recalibrated to provide unbiased estimates of absolute risk in such populations. Nevertheless, its limited discrimination ability at the individual level highlights the need to develop extended models with additional strong risk factors.

Adult weight gain, fat distribution and mammographic density in Spanish pre- and post-menopausal women (DDM-Spain).

High mammographic density (MD) is a phenotype risk marker for breast cancer. Body mass index (BMI) is inversely associated with MD, with the breast being a fat storage site. We investigated the influence of abdominal fat distribution and adult weight gain on MD, taking age, BMI and other confounders into account. Because visceral adiposity and BMI are associated with breast cancer only after menopause, differences in pre- and post-menopausal women were also explored. We recruited 3,584 women aged 45-68 years within the Spanish breast cancer screening network. Demographic, reproductive, family and personal history data were collected by purpose-trained staff, who measured current weight, height, waist and hip circumferences under the same protocol and with the same tools. MD was assessed in the left craniocaudal view using Boyd's Semiquantitative Scale. Association between waist-to-hip ratio, adult weight gain (difference between current weight and self-reported weight at 18 years) and MD was quantified by ordinal logistic regression, with random center-specific intercepts. Models were adjusted for age, BMI, breast size, time since menopause, parity, family history of breast cancer and hormonal replacement therapy use. Natural splines were used to describe the shape of the relationship between these two variables and MD. Waist-to-hip ratio was inversely associated with MD, and the effect was more pronounced in pre-menopausal (OR = 0.53 per 0.1 units; 95 % CI = 0.42-0.66) than in post-menopausal women (OR = 0.73; 95 % CI = 0.65-0.82) (P of heterogeneity = 0.010). In contrast, adult weight gain displayed a positive association with MD, which was similar in both groups (OR = 1.17 per 6 kg; 95 % CI = 1.11-1.23). Women who had gained more than 24 kg displayed higher MD (OR = 2.05; 95 % CI = 1.53-2.73). MD was also evaluated using Wolfe's and Tabár's classifications, with similar results being obtained. Once BMI, fat distribution and other confounders were considered, our results showed a clear dose-response gradient between the number of kg gained during adulthood and the proportion of dense tissue in the breast.

Impact of intermediate mammography assessment on the likelihood of false-positive results in breast cancer screening programmes.

OBJECTIVES: Breast cancer screening is offered to 100% of the target population in Spain and intermediate mammograms (IMs) are sometimes indicated. This study was aimed at analysing the frequency of IMs, the factors determining their recommendation, and their impact on the risk of false-positive results and the detection rate. METHODS: Data from 3,471,307 mammograms from Spanish breast cancer screening programmes were included. RESULTS: 3.36% of the mammograms were IMs. The factors associated with the use of IMs were age, initial screening, previous invasive tests, a familial history of breast cancer and use of hormone replacement therapy. In screening episodes with an IM, the probability of a false-positive result was 13.74% (95% CI: 13.43-14.05), almost double that in episodes without IMs (6.02%, 95% CI 5.99-6.05). In young women with previous invasive procedures, a familial history of breast cancer or hormone replacement therapy use who were undergoing their initial screen, this probability was lower when IMs were performed. IMs always increased the detection rate. CONCLUSIONS: The factors prompting IMs should be characterised so that radiologists can systematise their recommendations according to the presence of the factors maximising the benefits and minimising the adverse effects of this procedure. KEY POINTS: Intermediate mammograms in breast screening offer potential benefits but also disadvantages. Intermediate mammograms increase the false-positive rate except in specific groups. Intermediate mammograms reduce the false-positive rate in younger women and initial screens. Intermediate mammograms also reduce false-positive results in women with personal risk factors. Intermediate mammograms increase cancer detection mainly in women without risk factors.

Effect of false-positive results on reattendance at breast cancer screening programmes in Spain.

BACKGROUND: Mammography is the only breast screening method, we are aware of today, which is able to reduce mortality from breast cancer. Nevertheless, this procedure carries an inherent risk of false-positive screening mammogram. The association between these results and reattendance at the next scheduled screening mammogram is controversial. The aim of this study was to examine the effect of a false-positive screening mammogram and women's characteristics on reattendance in eight regional population-based breast cancer screening programmes in Spain. METHODS: This study included 1 383 032 women aged 44-67 years who were initially screened for breast cancer between 1990 and 2004. To investigate factors associated with reattendance, logistic regression models were used. RESULTS: The mean age of women at first screening was 53.6 years (SD = 6.1 years). Of 120 800 women with a false-positive screening mammogram, 78.3% returned for a subsequent screening mammogram compared with 81.9% of those with a negative result (P < 0.001). Multivariate analysis showed that women with a false-positive result at first screening mammogram were less likely to reattend (OR = 0.71; 95% CI 0.70-0.73) and that the likelihood was lower in those who had undergone invasive additional tests (OR = 0.56; 95% CI 0.53-0.59). CONCLUSION: A false-positive screening mammogram in the first screening negatively affected attendance at the subsequent screening. The results of this study could be useful to improve the screening process and to increase women's compliance.

[The Alliance for the Prevention of Colorectal Cancer in Spain. A civil commitment to society]. / Alianza para la Prevención del Cáncer de Colon en España: un compromiso cívico con la sociedad.

Colorectal cancer (CRC) is the most common malignant tumor in Spain, when men and women are considered together, and the second leading cause of cancer death. Every week in Spain over 500 cases of CRC are diagnosed, and nearly 260 people die from the disease. Epidemiologic estimations for the coming years show a significant increase in the number of annual cases. CRC is a perfectly preventable tumor and can be cured in 90% of cases if detected in the early stages. Population-based screening programs have been shown to reduce the incidence of CRC and mortality from the disease. Unless early detection programs are established in Spain, it is estimated that in the coming years, 1 out of 20 men and 1 out of 30 women will develop CRC before the age of 75. The Alliance for the Prevention of Colorectal Cancer in Spain is an independent and non-profit organization created in 2008 that integrates patients' associations, altruistic non-governmental organizations and scientific societies. Its main objective is to raise awareness and disseminate information on the social and healthcare importance of CRC in Spain and to promote screening measures, early detection and prevention programs. Health professionals, scientific societies, healthcare institutions and civil society should be sensitized to this highly important health problem that requires the participation of all sectors of society. The early detection of CRC is an issue that affects the whole of society and therefore it is imperative for all sectors to work together.

Alcohol, tobacco, and mammographic density: a population-based study.

Mammographic density (MD), or the proportion of the breast with respect to its overall area that is composed of dense tissue, is a strong risk factor for breast cancer. Studies support a positive association of mammographic density and alcohol drinking. This was a cross-sectional multicenter study based on 3584 women, aged 45-68 years, recruited from seven screening centers within the Spanish breast cancer screening program network. The association between MD, alcohol consumption and tobacco use was evaluated by using ordinal logistic models with random center-specific intercepts. We found a weak positive association between current alcohol intake and higher MD, with current alcohol consumption increasing the odds of high MD by 13% (OR = 1.13; 95% CI 0.99-1.28) and high daily grams of alcohol being positively associated with increased MD (P for trend = 0.045). There were no statistically significant differences in MD between smokers and non-smokers. Nevertheless, increased number of daily cigarettes and increased number of accumulated lifetime cigarettes were negatively associated with high MD (P for trend 0.017 and 0.021). The effect of alcohol on MD was modified by menopausal status and tobacco smoking: whereas, alcohol consumption and daily grams of alcohol were positively associated with higher MD in postmenopausal women and in women who were not currently smoking, alcohol consumption had no effect on MD in premenopausal women and current smokers. Our results support an association between recent alcohol consumption and high MD, characterized by a modest increase in risk at low levels of current consumption and a decrease in risk among heavier drinkers. Our study also shows how the effects of alcohol in the breast can be modified by other factors, such as smoking.

Childhood factors associated with mammographic density in adult women.

Growth and development factors could contribute to the development of breast cancer associated with an increase in mammographic density. This study examines the influence of certain childhood-related, socio-demographic and anthropometric variables on mammographic density in adult woman. The study covered 3574 women aged 45-68 years, participating in breast cancer-screening programmes in seven Spanish cities. Based on a craniocaudal mammogram, blind, anonymous measurement of mammographic density was made by a single radiologist, using Boyd's semiquantitative scale. Data associated with the early stages of life were obtained from a direct survey. Ordinal logistic regression and generalised linear models were employed to estimate the association between mammographic density and the variables covered by the questionnaire. Screening programme was introduced as a random effects term. Age, number of children, body mass index (BMI) and other childhood-related variables were used as adjustment variables, and stratified by menopausal status. A total of 811 women (23%) presented mammographic density of over 50%, and 5% of densities exceeded 75%. Our results show a greater prevalence of high mammographic density in women with low prepubertal weight (OR: 1.18; 95% CI: 1.02-1.36); marked prepubertal height (OR: 1.25; 95% CI: 0.97-1.60) and advanced age of their mothers at their birth (>39 years: OR: 1.28; 95% CI: 1.03-1.60); and a lower prevalence of high mammographic density in women with higher prepubertal weight, low birth weight and earlier menarche. The influence of these early-life factors may be explained by greater exposure to hormones and growth factors during the development of the breast gland, when breast tissue would be particularly susceptible to proliferative and carcinogenic stimulus.

Effect of start age of breast cancer screening mammography on the risk of false-positive results.

OBJECTIVE: To estimate the false-positive (FP) risk according to the start age of mammography screening (45-46 or 50-51 years). METHOD: Data from eight regions of the Spanish breast cancer screening programme from 1990 to 2006 were included (1,565,364 women). Discrete time-hazard models were used to ascertain the effect of age and time-related, programme-related and personal variables on FP leading to any further procedure and to invasive procedures (FPI). In a subset we estimated the differential FP risk of starting screening at 45-46 years (175,656 women) or 50-51 (251,275). RESULTS: A start age of 45-46 versus 50-51 years increased both FP (OR=1.20; 95%CI: 1.13-1.26) and FPI risks (OR=1.43 (95%CI: 1.18-1.73).Other factors increasing FP risk were premenopausal status (FP OR=1.26; 95%CI: 1.23-1.29 and FPI OR=1.22; 95%CI: 1.13-1.31), prior invasive procedures (FP OR=1.52; 95%CI: 1.47-1.57 and FPI (OR=2.08; 95%CI: 1.89-2.28) and family history (FP OR=1.16; 95%CI: 1.12-1.20 and FPI OR=1.26; 95%CI: 1.13-1.41). FP risk was increased by double reading (OR=1.36; 95%CI: 1.23-1.51) and FPI risk by double views (OR=1.34; 95%CI: 1.18-1.52). Both the cumulative FP and FPI risks were higher in women commencing screening at 45-46 years versus 50-51 years (33.30% versus 20.39% and 2.68% versus 1.76%). CONCLUSIONS: Starting screening earlier increases the cumulative risk of FP and FPI.

Evaluation of mammographic density patterns: reproducibility and concordance among scales.

BACKGROUND: Increased mammographic breast density is a moderate risk factor for breast cancer. Different scales have been proposed for classifying mammographic density. This study sought to assess intra-rater agreement for the most widely used scales (Wolfe, Tabár, BI-RADS and Boyd) and compare them in terms of classifying mammograms as high- or low-density. METHODS: The study covered 3572 mammograms drawn from women included in the DDM-Spain study, carried-out in seven Spanish Autonomous Regions. Each mammogram was read by an expert radiologist and classified using the Wolfe, Tabár, BI-RADS and Boyd scales. In addition, 375 mammograms randomly selected were read a second time to estimate intra-rater agreement for each scale using the kappa statistic. Owing to the ordinal nature of the scales, weighted kappa was computed. The entire set of mammograms (3572) was used to calculate agreement among the different scales in classifying high/low-density patterns, with the kappa statistic being computed on a pair-wise basis. High density was defined as follows: percentage of dense tissue greater than 50% for the Boyd, "heterogeneously dense and extremely dense" categories for the BI-RADS, categories P2 and DY for the Wolfe, and categories IV and V for the Tabár scales. RESULTS: There was good agreement between the first and second reading, with weighted kappa values of 0.84 for Wolfe, 0.71 for Tabár, 0.90 for BI-RADS, and 0.92 for Boyd scale. Furthermore, there was substantial agreement among the different scales in classifying high- versus low-density patterns. Agreement was almost perfect between the quantitative scales, Boyd and BI-RADS, and good for those based on the observed pattern, i.e., Tabár and Wolfe (kappa 0.81). Agreement was lower when comparing a pattern-based (Wolfe or Tabár) versus a quantitative-based (BI-RADS or Boyd) scale. Moreover, the Wolfe and Tabár scales classified more mammograms in the high-risk group, 46.61 and 37.32% respectively, while this percentage was lower for the quantitative scales (21.89% for BI-RADS and 21.86% for Boyd). CONCLUSIONS: Visual scales of mammographic density show a high reproducibility when appropriate training is provided. Their ability to distinguish between high and low risk render them useful for routine use by breast cancer screening programs. Quantitative-based scales are more specific than pattern-based scales in classifying populations in the high-risk group.

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.

Decline in age at menarche among Spanish women born from 1925 to 1962.

BACKGROUND: While the timing of reproductive events varies across populations, a downward trend in age at menarche has nevertheless been reported in most of the developed world over the past century. Given the impact of change in age at menarche on health conditions, this study sought to examine secular trends in age at menarche among women living in Navarre (Northern Spain) who participated in a population-based breast cancer screening programme. METHODS: The study was based on 110545 women born from 1925 to 1962. Trends were tested using a linear regression model, in which year of birth was entered continuously as the predictor and age at menarche (years) as the response variable, using size of town and region of birth as covariates. RESULTS: Among women born in Navarre between 1925 and 1962, age at menarche declined steadily from an average of 13.72 years in the 1925-1929 birth-cohorts to 12.83 years in the 1958-1962 birth-cohorts. Controlling for size of town or city of birth, age at menarche declined by an average of 0.132 years every 5 years over the period 1925-1962. This decline was greater in women born in rural versus urban settings. Trends were also different among regions of birth. CONCLUSION: We report a population-based study showing a downward trend in age of onset of menarche among Spanish women born in the period 1925-1962, something that is more pronounced among women born in rural settings and varies geographically.

Prevalence of healthy lifestyles against cancer in Spanish women.

Modifying behavior towards healthier lifestyles could prevent a significant number of malignant tumors. We evaluated the prevalence of healthy habits against cancer in Spanish women free of this disease, taking as a reference the recommendations for cancer prevention included in the European Code Against Cancer (ECAC), and we explored the characteristics associated with it. Our population comprised 3,584 women recruited in a population-based cross-sectional study carried out in 7 breast cancer screening programs. Information was directly surveyed and used to calculate a score based on ECAC recommendations referred to bodyweight, physical activity, diet, breastfeeding, tobacco, alcohol and hormone replacement therapy use. The degree of adherence was estimated with a score that evaluated null (0 points), partial (0.5 points) and full adherence (1 point) of each specific recommendation. Associations were explored using binary and ordinal logistic regression models. The median score was 5.7 out of 9 points. Recommendations with lower adherence were those related to intake of red/processed meat and foods high in salt (23% of total adherence), physical activity (24%) and body weight (29%), and recommendations with greater adherence where those related to hormone replacement therapy use (91%), vegetable intake (84%), alcohol (83%) and tobacco (61%). Overall adherence was better among older women, parous women, and in those living in rural areas, and worse among women with higher caloric intake. These recommendations should be evaluated periodically. Screening programs can be an appropriate place to disseminate this information.

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.

Thyroid disorders and mammographic density in Spanish women: Var-DDM study.

OBJECTIVES: The association between breast cancer (BC) and thyroid disorders has been widely explored with unclear results. Mammographic density (MD) is one of the strongest risk factor for BC. This study explores the relationship between thyroid diseases and MD in Spanish women. MATERIALS & METHODS: This cross-sectional study covered 2883 women aged 47-71 years participating in 7 BC screening programs in 2010. They allowed access to their mammograms, had anthropometrical-measures taken, and answered a telephonic epidemiological interview which included specific questions on thyroid diseases. Percentage of MD was assessed with a semiautomatic-computer tool (DM-scan) by two trained radiologists. We calculated the geometric mean of MD percentages (mean MD). Multivariable mixed linear regression models with random screening-center-specific intercepts were fitted, using log-transformed percentage of MD as dependent variable and adjusting for age, body mass index, menopausal status and other confounders. eß represents the relative increase of mean MD. RESULTS: 13.9% of the participants reported personal history of thyroid disease. MD was not associated to hyperthyroidism (eß:1.05, 95%CI: 0.82-1.36), hypothyroidism (eß:1.02, 95%CI: 0.75-1.38), thyroid nodules (eß:1.01, 95%CI: 0.85-1.19) or thyroid cancer (eß:1.03, 95%CI: 0.56-1.92). However, women with goiter had lower MD (mean MDno-goiter: 13.4% vs mean MDgoiter: 10.6%; eß:0.79, 95%CI: 0.64-0.98) and those with Hashimoto thyroiditis had higher MD (mean MDno-thyroiditis: 13.3% vs mean MDthyroidits: 25.8%; eß:1.94, 95%CI: 1.00-3.77). CONCLUSION: Functional thyroid disorders were not related to MD. However, MD was lower in women with goiter and higher in those reporting Hashimoto's thyroiditis. These relationships should be confirmed in future studies.

Sleep patterns, sleep disorders and mammographic density in spanish women: The DDM-Spain/Var-DDM study.

We explored the relationship between sleep patterns and sleep disorders and mammographic density (MD), a marker of breast cancer risk. Participants in the DDM-Spain/var-DDM study, which included 2878 middle-aged Spanish women, were interviewed via telephone and asked questions on sleep characteristics. Two radiologists assessed MD in their left craneo-caudal mammogram, assisted by a validated semiautomatic-computer tool (DM-scan). We used log-transformed percentage MD as the dependent variable and fitted mixed linear regression models, including known confounding variables. Our results showed that neither sleeping patterns nor sleep disorders were associated with MD. However, women with frequent changes in their bedtime due to anxiety or depression had higher MD (eß:1.53;95%CI:1.04-2.26).