Abstract
BackgroundAlthough the photosensitising effects of oestrogens may increase the impact of ultraviolet radiation (UVR) on melanoma risk, few prospective studies have comprehensively assessed the association between oestrogen-related factors and melanoma.MethodsWe examined the associations between reproductive factors, exogenous oestrogen use and first primary invasive melanoma among 167 503 non-Hispanic white, postmenopausal women in the NIH-AARP Diet and Health Study. Satellite-based ambient UVR estimates were linked to geocoded residential locations of participants at study baseline.ResultsIncreased risk of melanoma was associated with early age at menarche (≤10 vs ≥15 years: HR = 1.25, 95% CI: 0.92, 1.71; P for trend = 0.04) and late age at menopause (≥50 vs <45 years: HR = 1.34, 95% CI: 1.13, 1.59; P for trend = 0.001). The relationship between ambient UVR and melanoma risk was highest among women with age at menarche ≤10 years (HR per UVR quartile increase = 1.29; 95% CI: 1.05, 1.58; P-interaction = 0.02). Melanoma risk was not associated with parity, age at first birth, use of oral contraceptives or use of menopausal hormone therapy.ConclusionsOur findings suggest that increased melanoma risk is associated with early age at menarche and late age at menopause. Effect modification findings support the hypothesis that endogenous oestrogen exposure in childhood increases photocarcinogenicity. Future studies should include information on personal UVR exposure and sun sensitivity.
Highlights
The photosensitising effects of oestrogens may increase the impact of ultraviolet radiation (UVR) on melanoma risk, few prospective studies have comprehensively assessed the association between oestrogen-related factors and melanoma
When we stratify women by menopausal reason, we found a positive relationship between both age at natural menopause and melanoma risk and age at surgical menopause and melanoma risk
In this large cohort study, we prospectively evaluated the relationship between reproductive factors, exogenous oestrogen use and melanoma risk in US women residing in areas with substantial variation in ambient UVR
Summary
The photosensitising effects of oestrogens may increase the impact of ultraviolet radiation (UVR) on melanoma risk, few prospective studies have comprehensively assessed the association between oestrogen-related factors and melanoma. Cutaneous melanoma is the fifth most common cancer in the United States with an estimated 87,110 new cases and 9730 deaths expected in 2017.1,2 Well-established risk factors for melanoma include ultraviolet radiation (UVR) exposure,[3,4,5] pigmentary traits,[6,7] melanocytic nevi,[8,9] family history of melanoma (including high- and low-risk susceptibility genes6,10), inherited genetic conditions[11] and older age.[7,10] The age-specific incidence of melanoma is slightly greater among women than among men in the US until the age of 50 years, at which point the rates of melanoma in men begin to increase sharply, while incidence rates in women tend to level off.[12] The observation of these sex differences in the US and Europe,[13,14,15] historical case reports of melanoma diagnosed during pregnancy,[16] case reports of photosensitivity following oestrogen use including spectrophotometer testing confirming a high UV absorption for the administered oestrogen compound[17,18] and findings of oestrogen receptors in melanoma lesions[19,20] have motivated a number of epidemiological studies examining both endogenous oestrogen exposure (e.g. age at menarche, parity) and exogenous oestrogen use (e.g., oral contraceptives [OCs], menopausal hormone therapy [MHT]). Most of the epidemiological studies to date have been either case–control studies[21,22] or cohort studies in countries with relatively low levels of ambient UVR.[21,23,24] In addition, few studies have examined whether oestrogen-related factors modify the relationship between UVR exposure and melanoma.[23,25]
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