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    New Funding for California Pacific Medical Center Research Institute Scientists

    (October 3, 2013)

    California Pacific Medical Center Research Institute (CPMCRI) scientists Esther Wei and Peggy Cawthon were recently awarded competitive grants to continue their leading-edge research into illnesses impacting millions of Americans.

    Scientist Dr. Esther Wei received new funding from the Centers for Disease Control and Prevention to pursue research into the impact of night-shift work and sleep duration on the risk of colorectal adenoma—a precursor to colorectal cancer. Her study will assess women from the Nurses’ Health Study II, a large cohort of women who have been followed since 1989.

    During night-shift work, exposure to artificial light disrupts the body’s levels of melatonin. The hormone has been shown to suppress the initiation of cancer and possibly promote DNA repair. Night-shift work can reduce melatonin levels and thereby lead to an increased risk of tumorigenesis.

    “Although the link between night-shift work and colorectal cancer has been reported in one study, it is unknown at what stage night-shift work and melatonin levels may promote tumorigenesis,” said Dr. Wei. “We aim to study the earliest stages of the illness—the development of colorectal adenomas—to better understand the timing of night-shift work as a risk factor for colorectal carcinogenesis.”

    Sleep duration has been shown to increase the risk of breast, endometrial and colorectal cancer, although its relationship to the development of colorectal adenoma is poorly understood. Dr. Wei’s new study will explore the hypothesis that longer and shorter durations of sleep are associated with a higher risk of colorectal adenoma.

    “In addition to being the largest study of night-shift work, sleep duration and colorectal adenoma to date, this will be one of the first studies to evaluate whether directly measured melatonin levels are associated with colorectal adenoma,” said Dr. Wei. “Our findings will help lead to targeted interventions or tailored guidelines for night-shift workers who may be at increased risk of colorectal cancer.”

    Dr. Peggy Cawthon, Scientist at CPMCRI and the San Francisco Coordinating Center (SFCC) was awarded new funding from the National Institutes of Health (NIH) to investigate a novel measure of skeletal muscle mass, and whether results of this test are related to strength, physical performance, falls, fractures, disability and mortality in older men. The support from NIH leverages a public-private partnership with GlaxoSmithKline, and incorporates funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute on Aging.

    Dr. Cawthon’s project will build on the Osteoporotic Fractures in Men (MrOS) study, a large, prospective, multicenter trial begun by SFCC investigators in 2000 assessing healthy aging, specifically fracture risk and bone mass in men.

    While MrOS focused on osteoporotic outcomes, Dr. Cawthon’s new research will explore novel and more accurate means to test for sarcopenia—age-related loss of muscle that is accompanied by reduced strength and physical functioning.

    “Existing techniques to measure muscle mass are only weakly associated with functional outcomes,” noted Dr. Cawthon. “A clinically feasible, direct measure of muscle mass will enable a more complete understanding of the relationship between muscle mass and health.”

    The creatine dilution method measures the amount of creatinine—a by-product of muscle metabolism—in a single sample of urine after study subjects are given oral doses of deuterated creatine. Compared with existing tools to assess muscle mass (versus lean mass, which also includes connective tissues), creatine dilution may be faster, easier to implement, and more precise.

    “We suspect that men with decreased total body skeletal mass will have an increased risk of falls and fractures,” said Dr. Cawthon. “The creatine dilution method will help further our understanding of sarcopenia, and potentially identify men at risk of physical decline. Additionally, this new technique could be used to assess response to therapies aimed at improving strength or reversing age-related muscle loss.”