Wu AH, Stanczyk FZ, Wang R, Koh WP, Yuan JM, Yu MCSleep duration, spot urinary 6-sulfatoxymelatonin levels and risk of breast cancer among Chinese women in Singapore. Int J Cancer 132(4): 891-896

Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA. .
International Journal of Cancer (Impact Factor: 5.09). 02/2013; 132(4). DOI: 10.1002/ijc.27653
Source: PubMed


We previously reported an inverse association between sleep duration and breast cancer risk in the prospective, population-based Singapore Chinese Health Study (SCHS) cohort (Wu et al., Carcinogenesis 2008;29:1244-8). Sleep duration was significantly positively associated with 6-sulfatoxymelatonin (aMT6s) levels determined in a spot urine, but aMT6s levels in breast cancer cases were lacking (Wu et al., Carcinogenesis 2008;29:1244-8). We updated the sleep duration-breast cancer association with 14 years of follow-up of 34,028 women in the SCHS. In a nested case-control study conducted within the SCHS, randomly timed, prediagnostic urinary aMT6s concentrations were compared between 248 incident breast cancer and 743 individually matched cohort controls. Three female controls were individually matched to each case on age at baseline interview (within 3 years), dialect group, menopausal status, date of baseline interview (within 2 years), date of urine sample collection (within 6 months) and timing of urine collection during the day (within 1 hr). Cox proportional hazards and conditional regression models with appropriate adjustment for confounders were used to examine the sleep- and aMT6s-breast cancer relationships. Breast cancer risk was not significantly associated with sleep duration; adjusted odds ratio (OR) for 9+ vs. ≤6 hr is 0.89 [95% confidence interval (95% CI) = 0.64-1.22]. Prediagnostic aMT6s levels did not differ between breast cancer cases and matched controls; adjusted OR for highest versus lowest quartiles is 1.00 (95% CI = 0.64-1.54). We conclude that sleep duration is not significantly associated with breast cancer risk reduction. Melatonin levels derived from randomly timed spot urine are unrelated to breast cancer. Randomly timed, spot urine-derived melatonin levels are noninformative as surrogates of nocturnal melatonin production.

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    • "A S O Melatonin and breast cancer Wu et al. (2013) Singapore NCC 248 743 24-h spot urinary aMT6s 9 A B M O Travis et al. (2004) British Isles NCC 127 353 24-h urinary aMT6s 8 A B M O Schernhammer and Hankinson (2005) USA NCC 147 291 First spot morning urinary aMT6s 8 BEMO Schernhammer et al. (2008) Italy NCC 178 710 12-h overnight urinary aMT6s 9 A B E M O Schernhammer and Hankinson (2009) USA NCC 357 533 First spot morning urinary aMT6s 8 BEMO Schernhammer et al. (2010) Italy NCC 180 683 12-h overnight urinary aMT6s 9 A B E M S O A, age; B, BMI; CC, case–control study; CS, cohort study; E, ethanol-related conditions; H, hormone replacement therapy; LAN, light at night; M, menopausal status; NCC, nested case–control studies; O, others; P, physical activity; PCC, population-based case–control study; S, smoking. "
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    ABSTRACT: Evidence from observational studies on light at night (LAN) exposure, sleep duration, endogenous melatonin levels, and risk for breast cancer in women is conflicting. This led us to conduct a dose-response analysis of published observational data. Pertinent studies were identified by searching Medline, Web of Science, and EMBASE through April 2013. The dose-response relationship between sleep duration, urinary 6-sulphatoxymelatonin levels, and breast cancer was assessed using the restricted cubic spline model and by multivariate random-effects metaregression. A separate meta-analysis was also carried out to calculate the relative risks (RRs) with 95% confidence intervals (CIs) for breast cancer for the comparable categories or highest levels of exposure versus the lowest levels. Twelve case-control and four cohort studies were included in the analysis. High artificial LAN exposure is associated with an increased risk for breast cancer (RR=1.17, 95% CI: 1.11-1.23), but not ambient LAN exposure (RR=0.91, 95% CI: 0.78-1.07). The summary RR for breast cancer is 1.00 (95% CI: 0.995-1.01) for an increment of 1 h of sleep per night. No significant dose-response relationship between sleep duration and breast cancer was found either for the linearity test (Ptrend=0.725) or for the nonlinearity (Ptrend=0.091) test. An increasein of 15 ng/mg creatinine in urinary 6-sulphatoxymelatonin is associated with a 14% reduced risk for breast cancer (RR=0.86, 95% CI: 0.78-0.95), with a linear dose-response trend (Ptrend=0.003). There was no evidence of substantial heterogeneity or publication bias in the analysis. Our study adds to the evidence of LAN breast cancer theory. Further research in this area is warranted.
    Full-text · Article · May 2014 · European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP)
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    • "We identified 7 prospective studies, including the current study, of the risk of breast cancer in relation to the major urinary metabolite of melatonin, 6-sulfatoxymelatonin (8–12, 20). One study used measurements of urinary 6-sulfatoxymelatonin levels in spot urine samples (20) and was not considered eligible for the current meta-analysis because randomly timed, spot-urine-derived 6-sulfatoxymelatonin levels are not informative as surrogates of nocturnal melatonin production. "
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    ABSTRACT: It has been hypothesized that suppressed nocturnal melatonin production is associated with an increased risk of breast cancer, but results from several small prospective studies of the association have been inconclusive. We examined the association between nocturnal melatonin and breast cancer risk in a case-control study nested within the Guernsey III Study, a British prospective cohort study (1977-2009). Concentrations of 6-sulfatoxymelatonin were measured in prediagnostic first-morning urine samples from 251 breast cancer cases and 727 matched controls. Conditional logistic regression models were used to calculate odds ratios for breast cancer in relation to 6-sulfatoxymelatonin level. No significant association was found between 6-sulfatoxymelatonin level and breast cancer risk, either overall (for highest third vs. lowest, multivariable-adjusted odds ratio = 0.90, 95% confidence interval: 0.61, 1.33) or by menopausal status. However, in a meta-analysis of all published prospective data, including 1,113 cases from 5 studies, higher 6-sulfatoxymelatonin levels were associated with lower breast cancer risk (for highest fourth vs. lowest, odds ratio = 0.81, 95% confidence interval: 0.66, 0.99). In summary, we found no evidence that 6-sulfatoxymelatonin level in a first-morning urine sample was associated with breast cancer risk among British women. However, overall the published data suggest a modest inverse association between melatonin levels and breast cancer risk. Further data are needed to confirm this association.
    Full-text · Article · Jan 2014 · American journal of epidemiology
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    • "Finally, 12 articles fulfilling the inclusion criteria were included in the meta-analysis. Among these 12 articles, five studies reported breast cancer (Verkasalo et al., 2005; Pinheiro et al., 2006; Kakizaki et al., 2008b; Vogtmann et al., 2013; Wu et al., 2013), two studies on colorectal cancer (Jiao et al., 2013; Zhang et al., 2013), one each study on prostate cancer (Kakizaki et al., 2008a), endometrial cancer (Sturgeon et al., 2012), epithelial ovarian cancer (Weiderpass et al., 2012), thyroid cancer (Luo et al., 2013), and all type cancers (von Ruesten et al., 2012). "
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    ABSTRACT: To assess the risk of cancers associated with sleep duration using a meta-analysis of published cohort studies, we performed a comprehensive search using PubMed, Embase and Web of Science through October 2013. We combined hazard ratios (HRs) from individual studies using meta-analysis approaches. A random effect dose-response analysis was used to evaluate the relationship between sleep duration and cancer risk. Subgroup analyses and sensitivity analyses were also performed. Publication bias was evaluated using Funnel plots and Begg's test. A total of 13 cohorts from 12 studies were included in this meta-analysis, which included 723,337 participants with 15,156 reported cancer outcomes during a follow-up period ranging from 7.5 to 22 years. The pooled adjusted HRs were 1.06 (95% CI: 0.92, 1.23; P for heterogeneity=0.003) for short sleep duration, 0.91 (95% CI: 0.78, 1.07; P for heterogeneity <0.0001) for long sleep duration. In subgroup analyses stratified by cancer type, long duration of sleep showed an inverse relation with hormone-related cancer (HR=0.79; 95% CI: 0.65, 0.97; P for heterogeneity=0.009) and a greater risk of colorectal cancer (HR=1.29; 95% CI: 1.09, 1.52; P for heterogeneity=0.346). Further meta-analysis on dose-response relationships showed that the relative risks of cancer were 1.00 (95% CI: 0.99, 1.01; P for linear trend=0.9151) for one hour of sleep increment per day, and 1.00 (95% CI: 0.98, 1.01; P for linear trend=0.7749) for one hour of sleep increment per night. No significant dose-response relationship between sleep duration and cancer was found on non-linearity testing (P=0.5053). Our meta-analysis suggests a positive association between long sleep duration and colorectal cancer, and an inverse association with incidence of hormone related cancers like those in the breast. Studies with larger sample size, longer follow-up times, more cancer types and detailed measure of sleep duration are warranted to confirm these results.
    Full-text · Article · Dec 2013 · Asian Pacific journal of cancer prevention: APJCP
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