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Wegrzyn, Lani

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Wegrzyn

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Lani

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Wegrzyn, Lani
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    The association of body size in early to mid-life with adult urinary 6-sulfatoxymelatonin levels among night shift health care workers
    (BioMed Central, 2015) Ramin, Cody A; Massa, Jennifer; Wegrzyn, Lani; Brown, Susan B; Pierre-Paul, Jeffrey; Devore, Elizabeth; Hankinson, Susan; Schernhammer, Eva
    Background: Adult body mass index (BMI) has been associated with urinary melatonin levels in humans; however, whether earlier-life body size is associated with melatonin, particularly among night shift workers, remains unknown. Methods: We evaluated associations of birth weight, body shape (or somatotype) at ages 5 and 10, BMI at age 18 and adulthood, weight change since age 18, waist circumference, waist to hip ratio, and height with creatinine-adjusted morning urinary melatonin (6-sulfatoxymelatonin, aMT6s) levels among 1,343 healthy women (aged 32–53 at urine collection, 1996–1999) in the Nurses’ Health Study (NHS) II cohort. Using multivariable linear regression, we computed least-square mean aMT6s levels across categories of body size, and evaluated whether these associations were modified by night shift work. Results: Adult BMI was inversely associated with aMT6s levels (mean aMT6s levels = 34 vs. 50 ng/mg creatinine, comparing adult BMI ≥30 vs. <20 kg/m2; Ptrend <0.0001); however, other measures of body size were not related to aMT6s levels after accounting for adult BMI. Night shifts worked prior to urine collection, whether recent or cumulatively over time, did not modify the association between adult BMI and aMT6s levels (e.g., Pinteraction = 0.72 for night shifts worked within two weeks of urine collection). Conclusions: Our results suggest that adult BMI, but not earlier measures of body size, is associated with urinary aMT6s levels in adulthood. These observations did not vary by night shift work status, and suggest that adult BMI may be an important mechanism by which melatonin levels are altered and subsequently influence chronic disease risk.
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    Circadian Disruption, Mammographic Density and Risk of Breast Cancer
    (2016-01-19) Wegrzyn, Lani; Schernhammer, Eva; Tamimi, Rulla; Rosner, Bernard
    Humans are synchronized to the 24-hour day by the light-dark cycle of the environment. Through alteration of the suprachiasmatic nucleus (SCN), the brain’s circadian pacemaker, exposure to light at night (LAN) influences the functions in the body that operate with circadian regularity, including the endocrine, immune and digestive systems. The SCN also signals to the pineal gland to modulate production of melatonin, a hormone that has established antimitotic and antiproliferative properties, and has been shown to regulate estrogen and other hormones important in breast cancer etiology. People who work occupational night shifts are exposed to LAN and thereby experience circadian disruption, including delayed melatonin onset and reduction in peak nightly production. In 2007, the International Agency for Research on Cancer (IARC) at the World Health Organization (WHO) declared shift work that involves circadian disruption to be “probably carcinogenic to humans” (group 2A). The IARC working group cited strong experimental evidence from animals and supportive but limited human evidence from epidemiologic studies. This dissertation investigates several relationships on the pathway from rotating night shift work exposure to breast cancer, through mammographic breast density. Mammographic density, or the proportion of fibroglandular tissue in a woman’s breast as viewed on a mammogram, is the strongest risk factor for breast cancer, and has been reported as associated with a 4-6 fold increased risk of breast cancer. It is therefore, a reasonable intermediate endpoint for breast cancer. The analyses in this dissertation use data from two large longitudinal cohorts of female registered nurses in the United States, the Nurse’s Health Study and Nurse’s Health Study II, and are presented in a series of three papers. In the first paper, the prospective and long-term association of rotating night shift work and breast cancer is assessed with 24 years of follow-up, allowing for some analysis of the timing of exposure and tumor subtypes. In the second paper, the prospective relationship of rotating night shift work and mammographic density, as measured from screening mammograms, is evaluated. In the third paper, first morning void urinary 6-sulfatoxymelatonin, the main metabolite of melatonin excreted in urine, serves as a biomarker of circadian disruption, and is evaluated in relation to mammographic density in a cross-sectional analysis. Overall, this dissertation work provides evidence in favor of an association between long-term rotating night shift work and breast cancer, and suggests that long durations of shift work early in a nurse’s career may be of particular importance. Such shift work may occur in a time period, between puberty and breast involution due to childbirth or aging, during which breast tissue is vulnerable to carcinogenic influences. Rotating night shift work and a single measure of urinary melatonin did not appear to be related to mammographic breast density, suggesting that if rotating night shift work raises a woman’s risk of breast cancer, it is unlikely to do so through influence on mammographic density.