ToPCaP Researchers Receive Funding from National Institutes of Health to Study Impact of Circadian Rhythm and Prostate Cancer Risk
February 5, 2016

ToPCaP Researchers Receive Funding from National Institutes of Health to Study Impact of Circadian Rhythm and Prostate Cancer Risk

ToPCaP researchers Sarah Markt, Lorelei Mucci, Jennifer Rider, Ericka Ebot, Meir Stampfer, and Unnur Valdimarsdóttir, in collaboration with Lynne Wilkens (University of Hawaii) and Iona Cheng (CPIC), have received an NIH-funded R01 grant, active from 2016-2020, to investigate the association between disruption of the circadian rhythm and prostate cancer risk within a racially and ethnically diverse cohort of men.

Preliminary experimental data from Icelandic (AGES-Reykjavík) and US cohorts (the Health Professionals Follow-Up Study and Physicians Health Study) support the hypothesis that components of the circadian rhythm, including sleep problems, variants in circadian genes, and low melatonin levels, are associated with an increased risk of prostate cancer in cohorts of primarily Caucasian men. Given the known disparities in prostate cancer incidence and mortality as well as apparent differences in circadian rhythms by race/ethnicity, the researchers will extend these findings and test the circadian rhythm disruption hypothesis in the Multiethnic Cohort Study (MEC), a racially/ethnically diverse group of individuals from Hawaii and California ongoing since 1993. The MEC offers an unparalleled opportunity to test novel questions of circadian disruption and prostate cancer in an ethnically diverse population.

Investigating this hypothesis within a multi-ethnic cohort is appealing since African-American men have marked differences in melatonin levels, shorter circadian periods, and are at a disproportionately higher risk of developing and dying from prostate cancer compared to white and Asian-American men. The researchers will conduct a nested integrative molecular epidemiology case-control study in MEC among 1,648 incident prostate cancer cases and 3,296 controls, leveraging prospective biorepositories and long-term follow-up to integrate urinary biomarkers of melatonin, genetic variants, and questionnaire data to quantify the contribution of circadian disruption on prostate cancer initiation and progression.

The study of the circadian system is appealing as it represents a potentially modifiable factor (such as by altering sleep or melatonin levels) that could be translated into primary or secondary prevention efforts. The findings from this study also have the potential to disentangle and quantify the contributions of different proposed pathways involving circadian disruption and the etiology of prostate cancer.

Aims of the grant include:

    ·Evaluating whether low urinary 6-sulfatoxymelatonin levels – the primary melatonin metabolite – is associated with an increased risk of prostate cancer

    ·Assessing the association between genetic variation in core circadian rhythm genes with urinary levels of melatonin using existing genome-wide association study (GWAS) data

    ·Investigating the association between obesity and 6-sulfatoxymelatonin levels with prostate cancer risk