Michael S. Zens

Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls

Background Melanoma risk is related to sun exposure; we have investigated risk variation by tumour site and latitude. Methods We performed a pooled analysis of 15 case–control studies (5700 melanoma cases and 7216 controls), correlating patterns of sun exposure, sunburn and solar keratoses (three studies) with melanoma risk. Pooled odds ratios (pORs) and 95% Bayesian confidence intervals (CIs) were estimated using Bayesian unconditional polytomous logistic random-coefficients models. Results Recreational sun exposure was a risk factor for melanoma on the trunk (pOR = 1.7; 95% CI: 1.4–2.2) and limbs (pOR = 1.4; 95% CI: 1.1–1.7), but not head and neck (pOR = 1.1; 95% CI: 0.8–1.4), across latitudes. Occupational sun exposure was associated with risk of melanoma on the head and neck at low latitudes (pOR = 1.7; 95% CI: 1.0–3.0). Total sun exposure was associated with increased risk of melanoma on the limbs at low latitudes (pOR = 1.5; 95% CI: 1.0–2.2), but not at other body sites or other latitudes. The pORs for sunburn in childhood were 1.5 (95% CI: 1.3–1.7), 1.5 (95% CI: 1.3–1.7) and 1.4 (95% CI: 1.1–1.7) for melanoma on the trunk, limbs, and head and neck, respectively, showing little variation across latitudes. The presence of head and neck solar keratoses was associated with increased risk of melanoma on the head and neck (pOR = 4.0; 95% CI: 1.7–9.1) and limbs (pOR = 4.0; 95% CI: 1.9–8.4). Conclusion Melanoma risk at different body sites is associated with different amounts and patterns of sun exposure. Recreational sun exposure and sunburn are strong predictors of melanoma at all latitudes, whereas measures of occupational and total sun exposure appear to predict melanoma predominately at low latitudes.

Dealing with death data: individual hazards, mortality and bias

In ecology and evolution, we have barely begun to tap the information available in survival data. Who lives or dies, and why, is a large part of natural selection. In ecology, these are key questions for building better individual-based models of population and community dynamics. Powerful analytical tools exist to answer them, but the literature is scattered across disciplines, and its relevance is often obscured by inconsistent terminology and technical presentation. Here, we evaluate methods for the application of such tools to ecology and evolution. Analyses based on individual hazards of death are particularly promising, especially in combination with improvements in sampling design. The same methods can also reduce the largely unrecognized biases that plague population-level estimates of mortality rates.

A pooled analysis of melanocytic nevus phenotype and the risk of cutaneous melanoma at different latitudes.

An abnormal nevus phenotype is associated with an increased risk of melanoma. We report a pooled analysis conducted using individual nevus data from 15 case‐control studies (5,421 melanoma cases and 6,966 controls). The aims were to quantify the risk better and to determine whether relative risk is varied by latitude. Bayesian unconditional logistic random coefficients models were employed to study the risk associated with nevus characteristics. Participants with whole body nevus counts in the highest of 4 population‐based categories had a greatly increased risk of melanoma compared with those in the lowest category (pooled odds ratio (pOR) 6.9 (95% confidence interval (CI): 4.4, 11.2) for those aged <50 years and pOR 5.1 (95% CI: 3.6, 7.5) for those aged ≥50). The pOR for presence compared with absence of any clinically atypical nevi was 4.0 (95% CI: 2.8, 5.8). The pORs for 1–2 and ≥3 large nevi on the body compared with none were 2.9 (95% CI: 1.9, 4.3) and 7.1 (95% CI: 4.7, 11.6), respectively. The relative heterogeneities among studies were small for most measures of nevus phenotype, except for the analysis of nevus counts on the arms, which may have been due to methodological differences among studies. The pooled analysis also suggested that an abnormal nevus phenotype is associated most with melanomas on intermittently sun‐exposed sites. The presence of increased numbers of nevi, large nevi and clinically atypical nevi on the body are robust risk factors for melanoma showing little variation in relative risk among studies performed at different latitudes.

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 (≥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., ≥5 live births) had a particularly lower risk than women with later age at first birth (e.g., ≥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.

Diabetes and Risk of Bladder Cancer: Evidence from a Case-Control Study in New England

Diabetes is an emerging public health issue in the US, affecting 11% of Americans over the age of 20, with long‐term complications that include cardiovascular disease, retinopathy, neuropathy, and nephropathy. A recent meta‐analysis found that bladder cancer incidence was approximately 40% higher in individuals with diabetes; however, few studies considered duration or type of therapy and had limited adjustment for potentially confounding factors.

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.

Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure.

Background: Epidemiologic studies consistently find enhanced risk of basal cell carcinoma of the skin among individuals exposed to ionizing radiation, but it is unclear whether the radiation effect occurs for squamous cell carcinoma. It is also not known whether subgroups of individuals are at greater risk, eg, those with radiation sensitivity or high ultraviolet radiation exposure. Methods: We analyzed data from a case-control study of keratinocyte cancers in New Hampshire. Incident cases diagnosed in 1993–1995 and 1997–2000 were identified through a state-wide skin cancer surveillance system, and controls were identified through the Department of Transportation and Center for Medicare and Medicaid Service Files (n = 1121 basal cell carcinoma cases, 854 squamous cell carcinoma cases, and 1049 controls). Results: We found an association between history of radiation treatment and basal cell carcinoma. The association was especially strong for basal cell carcinomas arising within the radiation treatment field (odds ratio = 2.6; 95% confidence interval = 1.5–4.3), and among those treated with radiation therapy before age 20 (3.4; 1.8–6.4), those whose basal cell carcinomas occurred 40 or more years after radiation treatment (3.2; 1.8–5.8), and those treated with radiation for acne (11; 2.7–49). Similar age and time patterns of risk were observed for squamous cell carcinoma, although generally with smaller odds ratios. For basal cell carcinoma, early exposure to radiation treatment was a risk factor largely among those without a history of severe sunburns, whereas for squamous cell carcinoma, radiation treatment was a risk factor primarily among those with a sun-sensitive skin type (ie, a tendency to sunburn). Conclusions: Radiation treatment, particularly if experienced before age 20, seems to increase the long-term risk of both basal and squamous cell carcinomas of the skin. These risks may differ by sun exposure or host response to sunlight exposure.

Photosensitizing Agents and the Risk of Non-Melanoma Skin Cancer: A Population-Based Case–Control Study

It is well-known that ultraviolet (UV) light exposure and a sun sensitive phenotype are risk factors for the development of non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In this New Hampshire population-based case-control study, we collected data from 5,072 individuals, including histologically-confirmed cases of BCC and SCC, and controls via a personal interview to investigate possible associations between photosensitizing medication use and NMSC. After adjustment for potentially confounding factors (e.g. lifetime number of painful sunburns), we found a modest increase in risk of SCC (OR = 1.2, 95% CI = 1.0–1.4) and BCC (OR = 1.2, 95% CI = 0.9–1.5), in particular early-onset BCC, (≤ 50 years of age) (OR = 1.5, 95% CI = 1.1–2.1) associated with photosensitizing medication use. For SCC the association was strongest amongst those with tendency to sunburn rather than tan. We also specifically found associations with BCC, and especially early-onset BCC, and photosensitizing antimicrobials. In conclusion, certain commonly prescribed photosensitizing medications may enhance the risk of developing SCC, especially in individuals with a sun sensitive phenotype, and may increase the risk of developing BCC and incidence of BCC at a younger age.

Parity, early menopause and the incidence of bladder cancer in women: A case–control study and meta-analysis

INTRODUCTION Incidence rates of bladder cancer are notably higher in men than in women. While there is evidence that reproductive and hormonal risk factors may influence risk of bladder cancer, data are inconclusive. MATERIALS AND METHODS We examined reproductive, menstrual and hormonal use history in our population-based case-control study of bladder cancer in New Hampshire (NH), USA (n=207 women cases and n=463 women controls). Additionally, we performed a meta-analysis of the published literature. We used unconditional logistic regression analysis to compute adjusted odds ratios associated with each risk factor in the NH study. We combined these estimates with those from the published literature using inverse variance effects models. RESULTS In the NH study, a slightly decreased odds ratio was found among women who had ever had a birth compared to nulliparous women and an elevated odds ratio among women who underwent surgical menopause (bilateral oophorectomy), especially at an early age. No overall associations were found with oral contraceptive use or hormone replacement therapy. These findings were generally in agreement with the meta-analytic results for which the combined relative risk (RR) estimate was reduced among ever parous women (combined RR estimate for ever parous versus nulliparous=0.66, 95% confidence intervals [95% CI] 0.55-0.79) and elevated among those undergoing an early menopause (combined RR estimate for early versus late menopause=1.59, 95% CI 1.31-1.92). No consistent risk was observed for the other factors. DISCUSSION Some reproductive and menstrual factors appear to be related to the incidence of bladder cancer among women; but whether effects are due to female hormones is uncertain.

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, ≥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.