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Urinary melatonin and risk of ovarian cancer.

ABSTRACT: Melatonin has anti-carcinogenic properties, including modulation of estradiol production, cell cycle regulation, and promotion of apoptosis. Urinary melatonin has been inversely associated with breast cancer in some studies, but the association with ovarian cancer has not been investigated.We measured urinary 6-sulfatoxymelatonin (aMT6s) in nested ovarian cancer case-control studies in the Nurses' Health Study (NHS; n = 100 cases; 199 controls) and NHSII (n = 52 cases; 105 controls); samples were mainly from first morning voids. Controls were matched to cases on year of birth, menopause status, use of menopausal hormone therapy, and urine collection characteristics. We evaluated the association of tertiles of aMT6s, corrected for creatinine concentrations, with risk of ovarian cancer using conditional logistic regression. Models were adjusted for key ovarian cancer risk factors, and we additionally evaluated adjustment for usual sleep duration, snoring, and history of rotating night shift work.aMT6s was not significantly associated with risk of ovarian cancer. In multivariable models, the odds ratio comparing the highest tertile of aMT6s to the lowest was 0.79, 95 % confidence interval (CI) 0.40-1.56 in the NHS and 2.88, and 95 % CI in the NHSII 0.97-8.52. Additional adjustment for sleep habits and night shift work had little impact on the observed results. We observed no clear association between urinary melatonin and ovarian cancer risk.These results are consistent with our previous study in which we reported no association between night shift work and ovarian cancer; however, given the small sample size in our study, additional evaluation in larger studies is warranted.

SUBMITTER: Poole EM

PROVIDER: S-EPMC4567911 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Urinary melatonin and risk of ovarian cancer.

Poole Elizabeth M EM Schernhammer Eva E Mills Leigha L Hankinson Susan E SE Tworoger Shelley S SS

Cancer causes & control : CCC 20150730 10

<h4>Purpose</h4>Melatonin has anti-carcinogenic properties, including modulation of estradiol production, cell cycle regulation, and promotion of apoptosis. Urinary melatonin has been inversely associated with breast cancer in some studies, but the association with ovarian cancer has not been investigated.<h4>Methods</h4>We measured urinary 6-sulfatoxymelatonin (aMT6s) in nested ovarian cancer case-control studies in the Nurses' Health Study (NHS; n = 100 cases; 199 controls) and NHSII (n = 52 c ...[more]

PMID: 26223889

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Project description:Previous studies suggest that melatonin may act on cancer growth through a variety of mechanisms, most notably by direct anti-proliferative effects on breast cancer cells and via interactions with the estrogen pathway. Three genes are largely responsible for mediating the downstream effects of melatonin: melatonin receptors 1a and 1b (MTNR1a and MTNR1b), and arylalkylamine N-acetyltransferase (AANAT). It is hypothesized that genetic variation in these genes may lead to altered protein production or function. To address this question, we conducted a comprehensive evaluation of the association between common single nucleotide polymorphisms (SNPs) in the MTNR1a, MTNR1b, and AANAT genes and breast cancer risk among 2,073 cases and 2,083 controls, using a two-stage analysis of genome-wide association data among women of the Shanghai Breast Cancer Study. Results demonstrate two SNPs were consistently associated with breast cancer risk across both study stages. Compared with MTNR1b rs10765576 major allele carriers (GG or GA), a decreased risk of breast cancer was associated with the AA genotype (OR = 0.78, 95% CI = 0.62-0.97, P = 0.0281). Although no overall association was seen in the combined analysis, the effect of MTNR1a rs7665392 was found to vary by menopausal status (P-value for interaction = 0.001). Premenopausal women with the GG genotype were at increased risk for breast cancer compared with major allele carriers (TT or TG) (OR = 1.57, 95% CI = 1.07-2.31, P = 0.020), while postmenopausal women were at decreased risk (OR = 0.58, 95% 0.36-0.95, P = 0.030). No significant breast cancer associations were found for variants in the AANAT gene. These results suggest that common genetic variation in the MTNR1a and 1b genes may contribute to breast cancer susceptibility, and that associations may vary by menopausal status. Given that multiple variants in high linkage disequilibrium with MTNR1b rs76653292 have been associated with altered function or expression of insulin and glucose family members, further research may focus on clarifying this relationship.

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Urinary melatonin and risk of ovarian cancer.

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Urinary melatonin and risk of ovarian cancer.

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