Epidemiologic research has shown convincingly that certain phenotypic attributes are associated with increased relative risks of melanoma. Although such findings have intrinsic utility, there have been few attempts to translate such knowledge into estimates of disease burden suitable for framing public health policy. We aimed to estimate the population attributable fraction (PAF) for melanoma associated with melanocytic nevi using relative risk estimates derived from a systematic review and meta-analysis. We identified eligible studies using citation databases, followed by manual review of retrieved references. Of 49 studies identified, 25 and 23, respectively, were included in meta-analyses of atypical and common nevi. For people with ≥1 atypical nevi, the summary relative risk was 3.63 (95% confidence interval, 2.85-4.62), with a PAF of 0.25. The relative risk increased by 1.017 (95% confidence interval, 1.014-1.020) for each common nevus; however, significant heterogeneity in risk estimates was observed. We estimated that 42% of melanomas were attributable to having ≥25 common nevi (PAF 25-49 nevi = 0.15; PAF ≥50 nevi = 0.27), whereas PAFs for low nevus counts were modest (PAF 0-10 nevi = 0.04; PAF 11-24 nevi = 0.07). We modeled PAF under scenarios of varying nevus prevalence; the highest melanoma burden was always among those with high nevus counts (PAF range of 0.31-0.62 for ≥25 common nevi). Patients with ≥25 common nevi and/or ≥1 atypical nevi are a high-risk group, which might be targeted for identification, screening, and education. This work is the necessary first step in designing targeted preventive strategies for melanoma, which must now be overlaid with information about cost and utility. Cancer Prev Res; 3(2); 233-45. ©2010 AACR.

Epidemiologic research has demonstrated convincingly that certain pigmentary characteristics are associated with increased relative risks of melanoma; however there has been no comprehensive review to rank these characteristics in order of their importance on a population level. We conducted a systematic review of the literature and meta-analysis to quantify the contribution of pigmentary characteristics to melanoma, estimated by the population-attributable fraction (PAF). Eligible studies were those that permitted quantitative assessment of the association between histologically confirmed melanoma and hair colour, eye colour, skin phototype and presence of freckling; we identified 66 such studies using citation databases, followed by manual review of retrieved references. We calculated summary relative risks using weighted averages of the log RR, taking into account random effects, and used these to estimate the PAF. The pooled RRs for pigmentary characteristics were: 2.64 for red/red-blond, 2.0 for blond and 1.46 for light brown hair colour (vs. dark); 1.57 for blue/blue-grey and 1.51 for green/grey/hazel eye colour (vs. dark); 2.27, 1.99 and 1.35 for skin phototypes I, II and III respectively (vs. IV); and 1.99 for presence of freckling. The highest PAFs were observed for skin phototypes 1/II (0.27), presence of freckling (0.23), and blond hair colour (0.23). For eye colour, the PAF for blue/blue-grey eye colour was higher than for green/grey/hazel eye colour (0.18 vs. 0.13). The PAF of melanoma associated with red hair colour was 0.10. These estimates of melanoma burden attributable to pigmentary characteristics provide a basis for designing prevention strategies for melanoma.Among Caucasians, a large body of evidence suggests that pigmentary characteristics are important determinants of melanoma susceptibility; however, to date, there has been no comprehensive review to rank these characteristics in order of their importance on a population level. The identification of individuals at high risk of developing melanoma, who might be targeted for prevention and screening efforts, requires an understanding not only of the magnitude of the risk associated with each factor, but also their contribution to the burden of disease at the population level. The population-attributable fraction (PAF) is widely used to quantify the public health impact of putative causal factors, since it considers both the strength of association between risk factor and disease, as well as the prevalence of the factor in the community. 1 We have previously evaluated the PAF of melanoma associated with common and atypical nevi 2 and family history of melanoma. 3 The aim of this work was to evaluate systematically the most recent epidemiological evidence describing the relationship between melanoma and pigmentary characteristics and to use these data to estimate the fraction of melanomas attributable to these phenotypic characteristics. Material and MethodsA systematic review and meta-analysis was performed in accordance with MOOSE guidelin...

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Melanoma commonly clusters in families, and the recent identification of numerous genotypes predicting higher risks of melanoma has led to the widespread perception that this cancer is predominantly a genetic disease. We conducted a systematic review of the literature and meta-analysis to quantify the contribution of familial factors to melanoma, estimated by the population attributable fraction (PAF). Eligible studies were those that permitted quantitative assessment of the association between histologically confirmed melanoma and family history of the disease; we identified 22 such studies using citation databases, followed by manual review of retrieved references. We calculated summary RRs using weighted averages of the log RR, taking into account random effects, and used these to estimate the PAF. Overall, family history was associated with a significant 2-fold increased risk of melanoma (odds ratio, 2.06; 95% confidence interval, 1.72-2.45); however, there was significant heterogeneity (P = 0.01). The pooled estimate for population-based studies (n = 11) was 2.03 (1.70-2.43), and 2.51 (1.55-4.07) for clinic/hospital-based studies (n = 11), both with significant heterogeneity (P = 0.049 and P = 0.013, respectively). Two studies used record linkage to verify family history in relatives; the pooled risk estimate from these two studies was 2.52 (2.11-3.00) with no evidence of heterogeneity (P = 0.258). Estimates of PAF associated with a positive family history ranged from 0.007 for Northern Europe to 0.064 for Australia (0.040 for all regions combined). Our findings suggest that only a small percentage of melanoma cases (always <7%) are attributable to familial risk; the majority of melanomas are presumably attributable to other factors.

Objective: To assess whether the rates of Down syndrome births in Queensland vary according to rurality (ie, whether the mother lives in a rural or urban area) and type of antenatal care provider, and to consider any implications for antenatal care. Design and setting: Population‐based study of Down syndrome births in Queensland between 1990 and 2004, stratified by rurality and type of antenatal care provider (private obstetrician, public hospital or shared care). Results: Since 2000, there has been a large fall in maternal‐age‐adjusted rates of Down syndrome births among mothers living in urban areas (−14.3% per year; 95% CI, −22.7%, −5.0%) and among mothers receiving their antenatal care from private obstetricians (−27.5% per year; 95% CI, −37.6%, −15.8%). Similar decreases have not occurred among mothers living in rural areas (0.0%; 95% CI, −11.7%, 13.1%) or among mothers receiving antenatal care from public hospitals (+2.9%, 95% CI, −10.3%, 17.9%). Conclusion: Possible reasons for the observed trends include unequal access to antenatal screening; confusion about screening guidelines and protocols; late presentation for antenatal care; and differences in attitudes to screening and termination of pregnancy among expectant parents, such that they may choose not to have screening or not to act on a positive screening test result.