Biologic markers of sun exposure and melanoma risk in women: pooled case-control analysis.

A model has been proposed whereby melanomas arise through two distinct pathways dependent on the relative influence of host susceptibility and sun exposure. Such pathways may explain site-specific patterns of melanoma occurrence. To explore this model, we investigated the relationship between melanoma risk and general markers of acute (recalled sunburns) and chronic (prevalent solar keratoses) sun exposure, stratified by anatomic site and host phenotype. Our working hypothesis was that head and neck melanomas have stronger associations with solar keratoses and weaker associations with sunburn than trunk melanomas. We conducted a collaborative analysis using original data from women subjects of 11 case-control studies of melanoma (2,575 cases, 3,241 controls). We adjusted for potential confounding effects of sunlamp use and sunbathing. The magnitude of sunburn associations did not differ significantly by melanoma site, nevus count or histologic subtype of melanoma. Across all sites, relative risk of melanoma increased with an increasing number of reported lifetime "painful" sunburns, lifetime "severe" sunburns and "severe" sunburns in youth (p(trend) < 0.001), with pooled odds ratios (pORs) for the highest category of sunburns versus no sunburns of 3.22 [95% confidence interval (CI) 2.04-5.09] for lifetime "painful" sunburns, 2.10 (95%CI 1.30-3.38) for lifetime "severe" sunburns and 2.43 (95%CI 1.61-3.65) for "severe" sunburns in youth. Solar keratoses strongly increased the risk of head and neck melanoma (pOR 4.91, 95%CI 2.10-11.46), but data were insufficient to assess risk for other sites. Reported sunburn is strongly associated with melanoma on all major body sites.

Nevus density and melanoma risk in women: a pooled analysis to test the divergent pathway hypothesis.

A "divergent pathway" model for the development of cutaneous melanoma has been proposed. The model hypothesizes that melanomas occurring in people with a low tendency to develop nevi will, on average, arise more commonly on habitually sun-exposed body sites such as the head and neck. In contrast, people with an inherent propensity to develop nevi will tend to develop melanomas most often on body sites with large melanocyte populations, such as on the back. We conducted a collaborative analysis to test this hypothesis using the original data from 10 case-control studies of melanoma in women (2,406 cases and 3,119 controls), with assessment of the potential confounding effects of socioeconomic, pigmentary and sun exposure-related factors. Higher nevus count on the arm was associated specifically with an increased risk of melanoma of the trunk (p for trend = 0.0004) and limbs (both upper and lower limb p for trends = 0.01), but not of the head and neck (p for trend = 0.25). The pooled odds ratios for the highest quartile of nonzero nevus count versus none were 4.6 (95% confidence interval (CI) 2.7-7.6) for melanoma of the trunk, 2.0 (95% CI 0.9-4.5) for the head and neck, 4.2 (95% CI 2.3-7.5) for the upper limbs and 3.4 (95% CI 1.5-7.9) for the lower limbs. Aggregate data from these studies suggest that high nevus counts are strongly associated with melanoma of the trunk but less so if at all of the head and neck. This finding supports different etiologic pathways of melanoma development by anatomic site.

Anthropometric factors and risk of melanoma in women: a pooled analysis.

Anthropometric factors such as height, weight and body mass index are related to the occurrence of certain malignancies in women including cancers of the breast, ovary and endometrium. Several studies have investigated the relation between height and weight or body mass and the risk of cutaneous melanoma in women, but results have been inconsistent. We conducted a collaborative analysis of these factors using the original data from 8 case-control studies of melanoma in women (2,083 cases and 2,782 controls), with assessment of the potential confounding effects of socioeconomic, pigmentary and sun exposure-related factors. Women in the highest quartile of height had an increased risk of melanoma [pooled odds ratio (pOR) 1.3, 95% confidence interval (CI) 1.1-1.6]. We also found an elevated risk associated with weight gain in adult life of 2 kg or more (pOR 1.5, 95% CI 1.1-2.0). Stratifying by age at melanoma diagnosis (<50, >or=50 yr), we found this risk greater among women <50 yr of age. Associations were unaffected by adjustment for other known risk factors for melanoma. There was no evidence that the effects varied for different histologic subtypes of cutaneous melanoma. There was no association with body weight per se, body mass index, or body surface area, either recent or in young adulthood. In aggregate, data from these studies suggest that greater height and weight gain may be risk factors for cutaneous melanoma in women.

Pregnancy history and incidence of melanoma in women: a pooled analysis.

There is evidence that pregnancy history including age at first birth and parity may play a role in risk of cutaneous melanoma in women, although, epidemiological findings are inconsistent. We conducted a collaborative analysis of these factors using the original data from ten completed case-control studies (2391 cases and 3199 controls), and assessed the potential confounding effects of socioeconomic, pigmentary, and sun exposure-related factors. We found no overall association with ever having a live birth (pooled odds ratio (pOR) 0.95, 95% confidence interval (CI) 0.67-1.35). However, we detected a reduced risk of melanoma among women with higher parity (> or = 5 versus no live births pOR 0.76, 95% CI 0.49-1.18, each live birth pOR 0.95, 95% CI 0.91-0.99, p trend = 0.05). Women with both earlier age at first birth (e.g., <20 years) and higher parity (e.g., > or = 5 live births) had a particularly lower risk than women with later age at first birth (e.g., > or = 25 years) and lower parity (e.g., <5 live births) (pOR 0.33, 95% CI 0.14-0.75). The results are compatible with an effect of reproductive history-related factors on melanoma risk, but also could reflect differences in other factors, such as sun exposure history.