The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

Night shift work and osteoporosis - bone turnover markers among female blue-collar workers in Poland.

Osteoporosis is an important public health problem worldwide. Although many factors relating to bone structure have been described so far, the current knowledge on the occupational factors that may affect bone tissue metabolism is strongly limited. Literature data suggest that night shift work, via circadian rhythm disruption, may be considered a potential risk factor. To this date, only five epidemiological studies addressing this problem have been conducted worldwide. The outcomes of three studies confirmed such relationship, namely, a higher fracture risk was found among nurses with a long lifetime duration of night shift work in one study; and a lower bone mineral density was associated with occupational activity during night-time in two studies. In adults, the bone undergoes constant remodelling through bone resorption followed by bone formation. The various molecules released into the circulatory system during these processes are called bone turnover markers. We investigated the possible associations between night shift work and selected bone turnover markers: N-terminal propeptide of type I procollagen (P1NP), C-terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin, osteopontin, fibroblast growth factor 23 (FGF-23) and osteoprotegerin, measured in plasma of 189 female blue-collar workers. A significantly higher bone turnover rate was noted among the women working night shifts than among those working only during the day. This may potentially lead to a future development of osteoporosis in this population even if the macroscopic changes in the bone structure are not detectable. Night shift work is a prevailing occupational characteristics nowadays. It has been estimated that about 15-20% of the working population in Europe and the USA perform work under this system. Thus, the problem of osteoporosis can affect a large part of the working-age population.

Cadmium and volumetric mammographic density: A cross-sectional study in Polish women.

INTRODUCTION: Cadmium (Cd) is a heavy metal, which is widespread in the environment and has been hypothesized to be a metalloestrogen and a breast cancer risk factor. Mammographic density (MD) reflects the composition of the breast and was proposed to be used as a surrogate marker for breast cancer. The aim of our study was to investigate association between cadmium concentration in urine and mammographic density. METHODS: A cross-sectional study included 517 women aged 40-60 years who underwent screening mammography in Lódz, Poland. Data were collected through personal interviews and anthropometric measurements. Spot morning urine samples were obtained. The examination of the breasts included both craniocaudal and mediolateral oblique views. Raw data ("for processing") generated by the digital mammography system were analysed using Volpara Imaging Software, The volumetric breast density(%) and fibrograndular tissue volume(cm3) were determined. Cadmium concentration in urine was analysed using the standard ICP-MS method. RESULTS: After adjusting for key confounders including age, BMI, family breast cancer, mammographic device, season of the year of mammography, and age at menarche, an inverse association of Cd and volumetric breast density was found, which was attenuated after further adjustment for smoking. Associations of Cd with dense volume were null. CONCLUSIONS: These findings suggest that Cd is not positively associated with breast density, a strong marker of breast cancer risk, when examined in a cross-sectional fashion.

Night shift work and osteoporosis among female blue-collar workers in Poland - a pilot study.

Osteoporosis is an important public health problem worldwide. Although a number of factors that affect bone structure have been described; thus far, the current knowledge of occupational factors that may have an influence on bone tissue metabolism is strongly limited. Published studies indicate night shift work and the related circadian rhythm disruption may be considered as plausible underlying factors. The aim of the present study was to assess the potential association between night shift work and bone mineral density (BMD) among female blue-collar workers in Poland. A cross-sectional study was carried out among 194 female blue-collar workers >40 years of age employed in industrial plants. The operating system of work consisted of three work shifts clockwise rotation: morning (06:00-14:00 h), afternoon (14:00-22:00 h), and night (22:00-06:00 h), with five consecutive shifts per week followed by a free weekend. A questionnaire survey, based on a Polish version of The European vertebral osteoporosis study (EVOS) questionnaire, a validated instrument, was administered. Data on current job characteristics, job seniority, and lifetime duration of night shift work were also collected. BMD of the lumbar spine and hip (both total femur and femoral neck) was measured using dual-energy X-ray absorptiometry. Multivariate linear regression models were run, with bone mineralization parameters as dependent variables, as well as night work characteristics and important confounders. Statistical analysis was performed separately for premenopausal and postmenopausal women. The analyses adjusted for confounders did not reveal any significant differences between current or lifetime experience of night shift work and BMD among both premenopausal and postmenopausal women. However, the outcomes supported the well-established correlation with factors, such as age, BMI, and menopausal status. BMD at the three sites measured was significantly associated with BMI (p < .001) and inversely associated with age (p < .001) in the total study population. Postmenopausal women had significantly lower BMD than did premenopausal women (p < .001). The study findings indicate that in the population of Polish female blue-collar workers, the system of work does not seem to be associated with the development of osteoporosis.

Night shift work and osteoporosis: evidence and hypothesis.

Osteoporosis is an important public health problem worldwide. Among the countries with a very high population risk of fractures, there are those with the highest level of economic development. Osteoporotic fractures are the main cause of disability among elderly people, and the resultant disabilities require particularly large financial support associated not only with the direct treatment of the fracture but also with the necessity for long-term rehabilitation and care for the disabled person. Many well-established factors can have impact on bone mass and fracture risk. Recently, it has been hypothesized that working during nighttime which leads to endocrine disorders may have an indirect impact on bone physiology among night shift workers. Therefore, it can be presumed that the night shift work may contribute to the etiology of osteoporosis. The aim of our work was to make a review of the epidemiological evidence on the association between night shift work and bone mineral density or fracture risk as well as to discuss the potential biological mechanisms linking the work under this system with the development of osteoporosis. We have identified only four studies investigating the association between system of work and bone mineral density or fracture risk among workers. The findings of three out of four studies support the hypothesis. None of the studies has investigated a potential relationship between night shift work and bone turnover markers. Given that there have been no epidemiological studies in European countries that would concern working populations and the noticeable difference in the risk of osteoporosis between communities, further studies are warranted to elucidate the problem. It is presumed that further in-depth studies will not only identify the underlying factors of the disease but also contribute to developing guidelines for policy makers and employers for primary prevention of osteoporosis in workplace.

Sleep quality and methylation status of selected tumor suppressor genes among nurses and midwives.

Chronic sleep restriction may affect metabolism, hormone secretion patterns and inflammatory responses. Limited reports suggest also epigenetic effects, such as changes in DNA methylation profiles. The study aims to assess the potential association between poor sleep quality or sleep duration and the levels of 5-methylcytosine in the promoter regions of selected tumor suppressor genes. A cross-sectional study was conducted on 710 nurses and midwives aged 40-60 years. Data from interviews regarding sleep habits and potential confounders were used. The methylation status of tumor suppressor genes was determined via qMSP reactions using DNA samples derived from leucocytes. No significant findings were observed in the total study population or in the two subgroups of women stratified by the current system of work. A borderline significance association was observed between a shorter duration of sleep and an increased methylation level in CDKN2A among day working nurses and midwives. Further studies are warranted to explore this under-investigated topic.

Circadian gene methylation in rotating-shift nurses: a cross-sectional study.

Investigating the methylation status of the circadian genes may contribute to a better understanding of the shift work-related circadian disruption in individuals exposed to artificial light at night. In the present study, we determined the methylation status of the circadian genes associated with a shift work pattern among nurses and midwives participating in a cross-sectional study in Lodz, Poland. Quantitative methylation polymerase chain reaction assays were used to assess promoter CpG methylation in PER1, PER2, PER3, CRY1, CRY2, BMAL1, CLOCK, and NPAS2 in genomic DNA from whole blood of 347 women having a rotating-shift work schedule and 363 women working days only. The percentage of methylated reference (PMR) was assessed using fluorescent probes for PER1, PER2, PER3, CRY1, and NPAS2, and the percentage of gene methylation, as the methylation index (MI), using two sets of primers for BMAL1, CLOCK, and CRY2. We tested the possible association between current and lifetime rotating night-shift work characteristics and circadian gene methylation by using proportional odds regression model with blood DNA methylation, categorized into tertiles, and adjusted for age, current smoking status, folate intake and blood collection time. The findings indicated that CpG methylation in PER2 promoter was significantly decreased (P < 0.004) among nurses and midwives currently working rotating shifts, as compared with day-working nurses and midwives. The lower percentage of PER2 methylation was associated with a higher monthly frequency of current night duties (2-7 night shifts, and eight or more night shifts per month) (P = 0.012) and was associated at borderline significance (P = 0.092) with the lifetime duration of shift work (>10 ≤ 20 years and >20 ≤ 43 years of rotating-shift work) among nurses and midwives (N = 710). Moreover, women with a longer lifetime duration of shift work presented a lower status of PER1 methylation (P = 0.040) than did the women with up to 10 years of rotating-shift work. Long lifetime duration of shift work (> 10 years) among current rotating night-shift workers (N =  347) was associated with BMAL1 hypomethylation (P = 0.013). Among eight of the investigated circadian genes, only PER1, PER2, and BMAL1 showed differential methylation attributable to the rotating-shift work of nurses and midwives. The findings on blood-based DNA methylation in the circadian genes may provide a better insight into the mechanistic principles underlying the possible health effects of night-shift work but these should be verified in further studies recruiting larger populations of shift workers.

Sleep quality and methylation status of core circadian rhythm genes among nurses and midwives.

ABSTARCT Poor sleep quality or sleep restriction is associated with sleepiness and concentration problems. Moreover, chronic sleep restriction may affect metabolism, hormone secretion patterns and inflammatory responses. Limited recent reports suggest a potential link between sleep deprivation and epigenetic effects such as changes in DNA methylation profiles. The aim of the present study was to assess the potential association between poor sleep quality or sleep duration and the levels of 5-methylcytosine in the promoter regions of PER1, PER2, PER3, BMAL1, CLOCK, CRY1 CRY2 and NPAS2 genes, taking into account rotating night work and chronotype as potential confounders or modifiers. A cross-sectional study was conducted on 710 nurses and midwives (347 working on rotating nights and 363 working only during the day) aged 40-60 years. Data from in-person interviews about sleep quality, chronotype and potential confounders were used. Sleep quality and chronotype were assessed using Pittsburgh Sleep Quality Questionnaire (PSQI) and Morningness-Eveningness Questionnaire (MEQ), respectively. Morning blood samples were collected. The methylation status of the circadian rhythm genes was determined via quantitative methylation-specific real-time PCR assays (qMSP) reactions using DNA samples derived from leucocytes. The proportional odds regression model was fitted to quantify the relationship between methylation index (MI) as the dependent variable and sleep quality or sleep duration as the explanatory variable. Analyses were carried out for the total population as well as for subgroups of women stratified by the current system of work (rotating night shift/day work) and chronotype (morning type/intermediate type/evening type). A potential modifying effect of the system of work or the chronotype was examined using the likelihood ratio test. No significant findings were observed in the total study population. Subgroup analyses revealed two statistically significant associations between a shorter sleep duration and 1) methylation level in PER2 among day workers, especially those with the morning chronotype (OR = 2.31, 95%CI:1.24-4.33), and 2) methylation level in CRY2 among subjects with the intermediate chronotype, particularly among day workers (OR = 0.52, 95%CI:0.28-0.96). The study results demonstrated a positive association between average sleep duration of less than 6 hours and the methylation level of PER2 among morning chronotype subjects, and an inverse association for CRY2 among intermediate chronotype subjects, but only among day workers. Both the system of work and the chronotype turned out to be important confounders and modifiers in a number of analyses, making it necessary to consider them as potential covariates in future research on sleep deficiency outcomes. Further studies are warranted to explore this under-investigated topic.