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Key Contributions

Eva Schernhammer
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1. Work that led to WHO’s classification of shift work as a probable carcinogen. Ecologic and retrospective studies have earlier suggested a link between light at night, as encountered by night shift workers, and breast cancer risk, but the validity of these findings had been questions due to the many potential biases inherent to their study design. We published the first prospective cohort study to establish night shift work, via exposure to light at night, as a novel breast cancer risk factor (1a below). The findings from this paper were highly publicized and featured on national and international news media and they provided the impetus for several documentaries on light pollution and the effects of light at night on human health around the globe. Most significantly, this work, along with subsequent prospective analyses from our group, led WHO in 2007 to classify night shift work as a class 2A probable carcinogen.

  1. Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA. Rotating night shifts and risk of breast cancer in women participating in the nurses' health study. J Natl Cancer Inst. 2001;93(20):1563-8.
  2. Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Fuchs CS, Colditz GA. Night-shift work and risk of colorectal cancer in the nurses' health study. J Natl Cancer Inst. 2003;95(11):825-8.
  3. Schernhammer ES, Feskanich D, Liang G, Han J. Rotating night shift work and lung cancer risk among female nurses in the US. Am J Epidemiol 2013; 178(9):1434-1441. PMCID: PMC3813313  
  4. Straif K, Baan R, Grosse Y, Secretan B, Ghissassi FE, Bouvard V, Altieri A, Benbrahim-Ballaa L, Cogliano V, on behalf of the WHO International Agency for Research on Cancer Monograph Working Group*. Carcinogenicity of shift-work, painting, and fire-fighting. Lancet Oncol. 2007; 8(12):1065-66 (* member of the working group cited in the title of the manuscript).

2. Establishing urinary melatonin as a biomarker for sleep and the circadian system in large-scale observational studies and subsequently linking it to numerous disease outcomes. Melatonin is a hormone acutely sensitive to light exposure. In 2001, two independent research teams first established a then novel photoreceptor system in the human eye as the prime regulator of melatonin release from the pineal gland, and thus, more broadly, the human circadian system. Melatonin possesses a number of different oncostatic activities, though evidence was largely based on animal and in vitro studies. In 2005, after we established morning urinary melatonin as a feasible biomarker in large observational studies (ref. 2a), our group also – for the first time – demonstrated a significant association between this biomarker and breast cancer risk (ref.2b). The potential public health impact of these findings is substantial: from among the 992 women in the highest 6-sulfatoxymelatonin quartile, 40 developed breast cancer during follow-up, compared with 56 of the 992 of women in the lowest 6-sulfatoxymelatonin quartile. Our findings corroborate this hormone as a highly promising agent in breast cancer prevention and have laid the groundwork for an expert meeting (incl. Dr. Schernhammer) on Shift Work and Cancer at IARC/WHO aimed at improving exposure assessment (ref. 4a).

  1. Schernhammer ES, Rosner B, Willett WC, Laden F, Colditz GA, Hankinson SE. Epidemiology of urinary melatonin in women and its relation to other hormones and night work. Cancer Epidemiol Biomarkers Prev. 2004;13(6):936-43.
  2. Schernhammer ES, Hankinson SE. Urinary melatonin levels and breast cancer risk. J Natl Cancer Inst. 2005;97(14):1084-7.
  3. Schernhammer ES, Berrino F, Krogh V, Secreto G, Micheli A, Venturelli E, Sieri S, Sempos CT, Cavalleri A, Schünemann HJ, Strano S, Muti P. Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2008;100(12):898-905. PMCID: PMC2630389
  4. Brown S, Hankinson S, Eliassen AH, Reeves K, Wegrzyn L, Qian J, Arcaro K, Willett WC, Schernhammer ES. Urinary melatonin and the risk of breast cancer in the Nurses’ Health Study II. Am J Epidemiol 2015; 181(3):155-162. PMCID: PMC4312424

3. Demonstrating associations between sleep and shift work with cardiovascular disease, diabetes, and mortality. Expanding on her work establishing shiftwork as a probable carcinogen, Dr. Schernhammer has subsequently demonstrated the effects of shift work and sleep on the risk of numerous other chronic diseases, most notably cardiovascular disease. She showed ethnic variation in these associations and demonstrated that associations between shift work and e.g., diabetes risk varies depending on preferred sleep time, laying the groundwork for a refinement of exposure that captures phenotypic variation (i.e., circadian strain). By studying these associations, for the first time, in a Black population (as proposed in the current application), she continues to break new grounds in circadian epidemiology.

  1. Gu F, Han J, Laden F, Hu F, Pan A, Caporaso NE, Stampfer MJ, Kawachi I, Willett WC, Hankinson SE, Speizer F, Schernhammer ES. Total and cause-specific mortality of US nurses working rotating night-shifts Am J Prev Med 2015; 48(3):241-251. PMCID: PMC4272859
  2. Pan A, Schernhammer E, Sun Q, Hu F. Rotating Night Shift Work and the Risk of Type2 Diabetes: Two Propsective Cohort Studies in Women. PloS Med 2011; 8(12):e1001141. PMCID: PMC3232220
  3. Lieu SJ, Curhan GC, Schernhammer ES, Forman J. Rotating night shift work and disparate hypertension risk in African Americans. J Hypertens 2012; 30(1): 61-66. PMID: 22134389
  4. McMullan CF, Schernhammer ES, Hu F, Rimm E, Forman J. Melatonin secretion and the incidence of type 2 diabetes. JAMA 2013; 309(13):1388-1396. PMCID: PMC3804914

4. Dr. Schernhammer is leading the field in developing more refined exposure assessments for circadian disruption/strain and their application. Over the past years, leading experts in the field including Dr. Schernhammer have identified gaps in the exposure assessments that link circadian disruption to chronic disease risk. Dr. Schernhammer has conducted one of the largest field studies, using actigraphy, to collect real-life light exposure and melatonin measures among night shift workers from within the Nurses’ Health Studies. In another application of her research findings, she conducted a placebo-controlled trial of melatonin in breast cancer survivors, demonstrating beneficial effects of exogenous melatonin; she incorporates phenotypic information (i.e. clock genes, chronotype) to refine the definition and amount of circadian disruption (“circadian strain”) encountered by shift workers, and she has explored the interplay between work and sleep times and their additive effect on disease risk.

  1. Bonde JP, Hansen J, Kolstad HA, Mikkelsen S, Olsen JH, Blask DE, Härmä M, Kjuus H, de Koning HJ, Olsen J, Møller M, Schernhammer ES, Stevens RG, Åkerstedt T. Work at night and breast cancer: Report on evidence-based options for preventive actions. Scan J Work Environ Health October 2012; 38(4): 380-390.
  2. Miller D, Bierman A, Figueiro M, Schernhammer E, Rea, MS. Ecological measurements of light exposure, activity, and circadian disruption in real-world environments. Lighting Research and Technology 2011; 42(3): 271-284. PMCID: PMC3596178
  3. Bajaj A, Rosner B, Lockley S, Schernhammer ES. Validation of a light questionnaire with real life photopic lux measurements: The Harvard Light Exposure Assessment Questionnaire. Cancer Epidemiol Biomarker Prev 2011; 20(7):1341-1349. PMCID: PMC3340010
  4. Chen WY, Giobbie-Hurder A, Gantman K, Savoie JS, Scheib R, Schernhammer ES. A double-blind randomized controlled  trial of melatonin in breast cancer survivors: impact on sleep, mood, and hot flashes. Breast Cancer Research & Treatment 2014; 145(2): 381-388. PMCID: PMC4060962

5. Work that demonstrates a keen interest of Dr. Schernhammer in chronic disease risk factors more generally, has explored lifestyle factors as they relate to neurodegenerative disease (Parkinson’s disease, cognitive decline) and metabolic as well as molecular markers of breast and colon cancer risk. Folic acid and related vitamins B2, B6 and B12, are essential for DNA methylation and the production of purine and pyrimidine nucleotides required for DNA synthesis. Our work demonstrated, for the first time, that the reduced risk of colon cancer associated with replete folate status is limited to p53-overexpressing cancers (ref. 5a), thus offering a potential mechanism by which relative deficiency may promote colon carcinogenesis. We found several other important associations with molecular subtypes of colon cancer (e.g., ref.5d). Our work also implicated the IGF axis as one possible mechanism for the inverse associations between body fatness at young ages and adult BMI and premenopausal breast cancer risk, supporting the relevance of much earlier exposures to IGF-I (ref. 5b). This work, in addition to a number of pilot studies ruling out potential laboratory issues and cohort effects, has greatly furthered our understanding of the use of this biomarker in breast cancer studies. Several international projects of Dr. Schernhammer include, amongst others, the establishment of the largest population-based case-control study of Parkinson’s disease, worldwide (e.g., ref. 5c).

  1. Schernhammer ES, Ogino S, Fuchs C. Folate and vitamin B6 intake and colon cancer in relation to p53 mutational status. Gastroenterology. 2008;135(3):770-780. PMCID: PMC2634965
  2. Endogenous Hormones and Breast Cancer Collaborative Group*, Key TJ, Appleby PN, Reeves GK, Roddam AW. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncology 2010; 11(6):530-542 (member of the working group cited in the title of the manuscript) PMCID: PMC3113287
  3. Schernhammer ES, Hansen J, Ruijberg K, Wermuth L, Ritz B. Diabetes mellitus and the risk of developing Parkinson’s Disease in Denmark. Diabetes Care 2011; 34(5): 1102-1108. PMCID: PMC3114482
  4. Nishihara Reiko, Giovannucci E, Kawasaki T, Fuchs CS, Ogino S, Schernhammer ES. Dietary folate, alcohol, and B vitamins in relation to hypomethylation and the IGF2 DMR in colon cancer. Am J Clin Nutr 2014; 100(6):1479-1488. PMCID: PMC4232016