Reproductive factors and risk of melanoma: a population-based cohort study.

BACKGROUND: The association between reproductive factors and risk of cutaneous melanoma (CM) is unclear. We investigated this issue in the Norwegian Women and Cancer cohort study. OBJECTIVES: To examine the association between the reproductive factors age at menarche, menstrual cycle length, parity, age at first and last birth, menopausal status, breastfeeding duration and length of ovulatory life, and CM risk, overall and by histological subtypes and anatomical site. METHODS: We followed 165 712 women aged 30-75 years at inclusion from 1991-2007 to the end of 2015. Multivariable Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The mean age at cohort enrolment was 49 years. During a median follow-up of 18 years, 1347 cases of CM were identified. No reproductive factors were clearly associated with CM risk. When stratifying by histological subtype we observed significant heterogeneity (P = 0·01) in the effect of length of ovulatory life on the risk of superficial spreading melanoma (HR 1·02, 95% CI 1·01-1·04 per year increase) and nodular melanoma (HR 0·97, 95% CI 0·94-1·01 per year increase). When stratifying by anatomical site, menopausal status (HR 0·54, 95% CI 0·31-0·92, postmenopausal vs. premenopausal) and menstrual cycle length (HR 1·07, 95% CI 1·01-1·13, per day increase) were associated with CM of the trunk, and significant heterogeneity between anatomical sites was observed for menopausal status (P = 0·04). CONCLUSIONS: In this large population-based Norwegian cohort study, we did not find convincing evidence of an association between reproductive factors and risk of CM.

Is the matched extreme case-control design more powerful than the nested case-control design?

For time-to-event data, the study sample is commonly selected using the nested case-control design in which controls are selected at the event time of each case. An alternative sampling strategy is to sample all controls at the same (pre-specified) time, which can either be at the last event time or further out in time. Such controls are the long-term survivors and may therefore constitute a more 'extreme' comparison group and be more informative than controls from the nested case-control design. We investigate this potential information gain by comparing the power of various 'extreme' case-control designs with that of the nested case-control design using simulation studies. We derive an expression for the theoretical average information in a nested and extreme case-control pair for the situation of a single binary exposure. Comparisons reveal that the efficiency of the extreme case-control design increases when the controls are sampled further out in time. In an application to a study of dementia, we identified Apolipoprotein E as a risk factor using a 1:1 extreme case-control design, which provided a hazard ratio estimate with a smaller standard error than that of a 2:1 nested case-control design.

Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population-based Janus Cohort.

BACKGROUND: Breslow thickness is the most important prognostic factor of localized cutaneous melanoma (CM), but associations with anthropometric factors have been sparsely and incompletely investigated. OBJECTIVES: To examine prediagnostic body mass index (BMI), body surface area (BSA), and height, weight and weight change in relation to Breslow thickness, overall and by anatomical site and histological subtype; and to assess possible nonlinear associations between these anthropometric factors and Breslow thickness. METHODS: CMs in the Janus Cohort were identified between 1972 and 2014. Linear regression was used to estimate geometric mean ratios (GMRs) of Breslow thickness with 95% confidence intervals (CIs) according to anthropometric factors. Restricted cubic splines in generalized linear models predicted adjusted mean Breslow thickness, and were used to assess possible nonlinear relationships. RESULTS: Of 2570 cases of CM, obese patients had a GMR of 1·16 (95% CI 1·04-1·30) of Breslow thickness vs. normal-weight patients. For BSA and weight, quintile 5 showed GMRs of 1·13 (95% CI 1·00-1·27) and 1·17 (95% CI 1·03-1·33) of Breslow thickness vs. quintile 1, respectively. Associations seemed restricted to superficial spreading melanomas and CMs on the trunk and lower limbs. The associations plateaued at an adjusted mean Breslow thickness of about 2·5 mm (BMI 29 kg m-2 , BSA 2·05 m2 and weight 90 kg), before declining for the highest values. No associations were found for height and weight change. CONCLUSIONS: This large case-series of incident CM demonstrated positive associations between BMI, BSA, weight and Breslow thickness, and suggested that behavioural or other mechanisms apply at high values.

Hyperemesis gravidarum and birth outcomes-a population-based cohort study of 2.2 million births in the Norwegian Birth Registry.

OBJECTIVE: To study associations between hyperemesis gravidarum (HG) and birth outcomes. DESIGN: Population-based cohort study. SETTING: Norway. SAMPLE: Singleton births in the Norwegian Birth Registry, 1967-2009 (n = 2 270 363). METHODS: Multiple logistic regression was applied to study associations between HG and dichotomous outcomes; multiple linear regression to study associations between HG, birthweight and gestational length. Generalised estimating equations were applied to obtain valid standard errors. Sub-analysis on data with available information on smoking was conducted (1999-2009). MAIN OUTCOME MEASURES: Small and large for gestational age (SGA/LGA), Apgar score after 5 minutes, very preterm and preterm birth (VPTB/PTB), perinatal death, stillbirth, neonatal death, birthweight and gestational length. RESULTS: No associations between HG and adverse pregnancy outcomes were observed in crude analyses, except for VPTB (odds ratio [OR] 0.79, 95% CI 0.67-0.93). In adjusted analysis, HG was associated with perinatal death (OR 1.27, 95% CI 1.08-1.48). Inverse associations were observed between HG and VPTB (OR 0.80, 95% CI 0.68-0.94) and LGA (OR 0.95, 95% CI 0.90-0.99). Sub-analyses showed no associations between HG and perinatal death (OR 1.29, 95% CI 0.91-1.83). The inverse associations between HG, VPTB and LGA were strengthened (OR 0.66, 95% CI, 0.48-0.91 and OR 0.86, 95% CI 0.79-0.93, respectively). Exposed babies had reduced birthweight and gestational length compared with unexposed, adjusted difference - 21.4 g and - 0.5 days, respectively. Adjustment for smoking slightly strengthened the impact of HG on birthweight. CONCLUSIONS: Inverse associations for HG and VPTB and LGA were observed. HG was associated with slight reductions in birthweight and gestational age.

Is hyperemesis gravidarum associated with placental weight and the placental weight-to-birth weight ratio? A population-based Norwegian cohort study.

INTRODUCTION: Studies have suggested a link between placental weight, placental weight-to-birth weight ratio (PW/BW) and adult health. Hyperemesis gravidarum (HG) may also have implications for adult health. No studies on HG and placental characteristics have been identified. We therefore explored the relationship between HG, placental weight and the PW/BW-ratio in a population-based cohort. METHODS: Singleton births to primiparous women between 1999 and 2009 with data on HG, placental weight and birth weight in the Medical Birth Registry of Norway (MBRN) comprised the study base (n = 200,390). HG was defined through ICD-10 code 021.0, 021.1 and 021.9. Gender and gestational age specific percentile curves for placenta weight and PW/BW ratio were used to define those below the 10th and above the 90th percentile of both outcomes. Associations between HG and dichotomous outcomes were studied by multiple logistic regression. Multiple linear regression was applied to study placental weight as a continuous variable. Male and female offspring were analyzed separately. RESULTS: The prevalence of HG was 1.2%. Women with HG and female offspring had significantly higher risk of a PW/BW-ratio above the 90th percentile (OR = 1.17, 95% CI: 1.03-1.34). HG and PW/BW-ratio below the 10th percentile were inversely associated (OR = 0.70, 95% CI: 0.56-0.89). For male offspring no association was observed for HG and PW/BW-ratio below the 10th or above the 90th percentile. DISCUSSION/CONCLUSIONS: We observed positive associations between HG and high PW/BW ratio limited to female offspring only. The high PW/BW-ratio suggests that there may be a possible link between HG and adult health.