Smoking history and breast cancer risk by pathological subtype: MCC-Spain study.

INTRODUCTION: The role of cigarette smoking on breast cancer risk remains controversial, due to its dual carcinogenic-antiestrogenic action. METHODS: In the population-based multi-case-control study (MCC-Spain), we collected epidemiological and clinical information for 1733 breast cancer cases and 1903 controls, including smoking exposure. The association with breast cancer, overall, by pathological subtype and menopausal status, was assessed using logistic and multinomial regression models. RESULTS: Smokers had higher risk of premenopausal breast cancer, particularly if they had smoked ≥30 years (AOR=1.75; 95% CI: 1.04-2.94), although most estimates did not achieve statistical significance. In contrast, among postmenopausal women, smoking was associated with lower risk of breast cancer, mainly in overweight and obese women. The strongest risk reductions were observed among postmenopausal women who had stopped smoking ≥10 years before cancer diagnosis, particularly for HER2+ tumors (AOR=0.28; 95% CI: 0.11-0.68); p for heterogeneity = 0.040). Also, those who had smoked <10 pack-years (AOR=0.68; 95% CI: 0.47-0.98) or 10-25 pack-years (AOR=0.62; 95% CI: 0.42-0.92) during their lifetime were at a reduced risk of all breast cancer subtypes (p for heterogeneity: 0.405 and 0.475, respectively); however, women who had smoked more than 25 pack-years showed no reduced risk. CONCLUSIONS: Menopausal status plays a key role in the relationship between tobacco and breast cancer for all cancer subtypes. While smoking seems to increase the risk in premenopausal woman, it might be associated to lower risk of breast cancer among postmenopausal women with excess weight.

Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study).

BACKGROUND: Some studies have reported an inverse association between type 2 diabetes mellitus (T2DM) and prostate cancer (PCa), but results on this issue are still inconsistent. In this study, we evaluate whether this heterogeneity might be related to differences in this relationship by tumour or by individual genetic susceptibility to PCa. METHODS: We studied 1047 incident PCa cases and 1379 randomly selected controls, recruited in 7 Spanish provinces for the population-based MCC-Spain case-control. Tumour were classified by aggressiveness according to the International Society of Urological Pathology (ISUP), and we constructed a PCa polygenic risk score (PRS) as proxy for genetic susceptibility. The epidemiological questionnaire collected detailed self-reported data on T2DM diagnosis and treatment. The association between T2DM status and PCa was studied by fitting mixed logistic regression models, and, for its association by aggressiveness of PCa, with multinomial logistic regression models. To evaluate the possible modulator role of PRS in this relationship, we included the corresponding interaction term in the model, and repeated the analysis stratified by PRS tertiles. RESULTS: Globally, our results showed an inverse association between T2DM and overall PCa limited to grade 1 tumours (ORISUP = 1: 0.72; 95% CI: 0.53-0.98), which could be compatible with a detection bias. However, PCa risk also varied with duration of diabetes treatment -inversely to metformin and positively with insulin-, without differences by aggressiveness. When we considered genetic susceptibility, T2DM was more strongly associated with lower PCa risk in those with lower PRS (ORtertile 1: 0.31; 95% CI: 0.11-0.87), independently of ISUP grade. CONCLUSIONS: Our findings reinforce the need to include aggressiveness and susceptibility of PCa, and T2DM treatments in the study of the relationship between both diseases.

Occupation, occupational exposures and mammographic density in Spanish women.

INTRODUCTION: Mammographic density (MD), the proportion of radiologically dense breast tissue, is a strong risk factor for breast cancer. Our objective is to investigate the influence of occupations and occupational exposure to physical, chemical, and microbiological agents on MD in Spanish premenopausal women. METHODS: This is a cross-sectional study based on 1362 premenopausal workers, aged 39-50, who attended a gynecological screening in a breast radiodiagnosis unit of Madrid City Council. The work history was compiled through a personal interview. Exposure to occupational agents was evaluated using the Spanish job-exposure matrix MatEmESp. MD percentage was assessed using the validated semi-automated computer tool DM-Scan. The association between occupation, occupational exposures, and MD was quantified using multiple linear regression models, adjusted for age, educational level, body mass index, parity, previous breast biopsies, family history of breast cancer, energy intake, use of oral contraceptives, smoking, and alcohol consumption. RESULTS: Although no occupation was statistically significantly associated with MD, a borderline significant inverse association was mainly observed in orchard, greenhouse, nursery, and garden workers (ß = -6.60; 95% confidence interval (95%CI) = -14.27; 1.07) and information and communication technology technicians (ß = -7.27; 95%CI = -15.37; 0.84). On the contrary, a positive association was found among technicians in art galleries, museums, and libraries (ß = 8.47; 95%CI = -0.65; 17.60). Women occupationally exposed to fungicides, herbicides, and insecticides tended to have lower MD. The percentage of density decreased by almost 2% for every 5 years spent in occupations exposed to the mentioned agents. CONCLUSIONS: Although our findings point to a lack of association with the occupations and exposures analyzed, this study supports a deeper exploration of the role of certain occupational agents in MD, such as pesticides.

Toenails as biomarker of exposure to essential trace metals: A review.

Health problems associated with essential trace metals can result from both inadequate (i.e., low intake) and excessive exposures (i.e., from environmental and/or occupational source). Thus, measuring the exposure level is a real challenge for epidemiologists. Among non-invasive biomarkers that intend to measure long-term exposure to essential trace metals, the toenail is probably the biological matrix with the greatest potential. This systematic review collects the current evidence regarding the validity of toenail clippings as exposure biomarker for trace metals such as boron, cobalt, copper, iron, manganese, molybdenum, selenium, silicon, vanadium and zinc. Special attention was paid to the time-window of exposure reflected by the toenail, the intraindividual variability in exposure levels over time in this matrix, and the relationship of toenail with other biomarkers, personal characteristics and environmental sources. Our search identified 139 papers, with selenium and zinc being the most studied elements. The variability among studies suggests that toenail levels may reflect different degrees of exposure and probably correspond to exposures occurred 3-12 months before sampling (i.e., for manganese/selenium). Few studies assessed the reproducibility of results over time and, for samples obtained 1-6 years apart, the correlation coefficient were between 0.26 and 0.66. Trace metal levels in toenails did not correlate well with those in the blood and urine and showed low-moderate correlation with those in the hair and fingernails. Available data suggests that for some elements (Se, Mn, Zn) toenail concentrations reflect long-term external exposures in fairly reproducible levels, while for other metals, this association has not yet been assessed. Among dietary factors, only toenail selenium showed clear associations with the intake of supplements or specific foods. The toenail levels could also represent occupational exposure, for instance, Mn exposure in welders. The scarcity of information on other essential trace elements, together with the great heterogeneity among studies makes the validation of the usage of toenails as biomarkers of exposure to these elements difficult. Standardization of sample collection, quality control, analytical techniques and reporting procedures might facilitate further research focused on the clear understanding of the significance of essential levels in this promising matrix and would enhance its utility in epidemiological research.

The burden of premature mortality in Spain using standard expected years of life lost: a population-based study.

BACKGROUND: Measures of premature mortality have been used to guide debates on future health priorities and to monitor the population health status. Standard expected years of life lost (SEYLL) is one of the methods used to assess the time lost due to premature death. This article affords an overview of premature mortality in Spain for the year 2008. METHODS: A population-based study was conducted estimating SEYLL by sex and age groups. SEYLL, a key component of the disability-adjusted life years measure of disease burden, was calculated using Princeton West standard life tables with life expectancy at birth fixed at 80 years for males and 82.5 years for females. Population data and specific death records were obtained from the official registers of the National Institute of Statistics. All data were analysed and prepared in GesMor and Epidat software packages. RESULTS: The burden of premature mortality was estimated at 2.1 million SEYLL when age at death is taken into account. Males lost 60.9% and females lost 39.1% of total SEYLL. Malignant tumors (34.5%) and cardiovascular diseases (24.0%) were the leading categories in terms of SEYLL. Ischaemic heart disease (8.5%) and lung cancers (8.0%) were the most common specific causes of SEYLL followed by cerebrovascular diseases (5.9%), colorectal cancer (4.1%), road traffic accidents (3.5%), Alzheimer and other dementias (2.9%), chronic obstructive pulmonary disease (2.8%), breast cancer (2.8%) and suicides (2.6%). CONCLUSIONS: In Spain, premature mortality was essentially due to chronic non-communicable diseases. Data provided in this study are relevant for a more balanced health agenda aimed at reducing the burden of premature mortality. This study also represents a first step in estimating the overall burden of disease in terms of premature death and disability.