Childhood cancer incidence in relation to sunlight exposure

Background:

There is increasing interest in the possible association between cancer incidence and vitamin D through its role as a regulator of cell growth and differentiation. Epidemiological studies in adults and one paediatric study suggest an inverse association between sunlight exposure and cancer incidence.

Methods:

We carried out an ecological study using childhood cancer registry data and two population-level surrogates of sunlight exposure, (1) latitude of the registry city or population centroid of the registry nation and (2) annual solar radiation. All models were adjusted for nation-level socioeconomic status using socioeconomic indicators.

Results:

Latitude and radiation were significantly associated with cancer incidence, and the direction of association was consistent between the surrogates. Findings were not consistent across tumour types.

Conclusion:

Our ecological study offers some evidence to support an association between sunlight exposure and risk of childhood cancer.     

Season of cancer diagnosis exerts distinct effects upon short‐ and long‐term survival

Several epidemiological studies have shown an association between the season in which certain cancers are diagnosed and survival, with diagnosis in summer and autumn being associated with better survival. In this study, we have added resolution to the analysis of seasonality in cancer survival by considering mortality within several nonoverlapping time periods following diagnosis, thereby quantifying the separate contributions of mechanisms operating in the short term and in the longer term. We found evidence of seasonality acting on mortality within 2 distinct periods following diagnosis. Diagnosis in the summer was associated with substantially decreased mortality within the first month of diagnosis compared with winter in men with prostate cancer, those of both sexes with colorectal or lung cancer, and most strikingly, amongst women with breast cancer (hazard ratio 0.81 [95% confidence interval 0.75–0.86]). Adjusting for monthly variations in general mortality greatly attenuated the seasonal effects on short‐term mortality. At long‐term follow‐up (>5 years), there was a consistent shift in the seasonality pattern, with autumn diagnosis alone being associated with decreased mortality, both in female breast cancer cases and in lung cancer cases of both sexes. We conclude that the higher survival observed amongst patients diagnosed in summer and autumn is predominantly a short‐term phenomenon that is largely attributable to generally higher mortality in winter. However, the distinct mortality reduction observed in the long term amongst those diagnosed in the autumn, especially amongst breast cancer patients, may indicate the presence of a seasonally variable protective mechanism. © 2008 Wiley‐Liss, Inc.     

Season of diagnosis has no effect on survival from malignant melanoma

Diagnosis in summer had been shown to be associated with better survival from some cancers, but such studies on malignant melanoma where sun exposure is a risk factor for disease are rare. We evaluated seasonality in melanoma diagnosis and its effect on survival in Victoria, Australia using 26,060 cases reported to the population‐based Victorian Cancer Registry during 1986–2004. To estimate the amplitude of the seasonal variation, we calculated the ratio of the number of melanoma cases diagnosed in summer to that in winter. Linear regression was undertaken to assess the variation in thickness, the main prognostic indicator for melanoma, by season of diagnosis adjusting for sex, anatomical site, year of diagnosis and age at diagnosis. We modeled excess mortality using Poisson regression controlling for possible confounders in order to study the effect of season of diagnosis on survival. An overall 46% summer diagnostic excess was evident (summer‐to‐winter ratio 1.46; 95% CI 1.41, 1.52). Results of linear regression showed that melanoma diagnosed in winter were thicker than those diagnosed in any other season (percentage difference in thickness ?2.01, ?6.97 and ?10.68 for spring, summer and autumn, respectively; p < 0.001). In the Poisson regression model of relative survival, cases diagnosed in spring, summer or autumn had slightly lower excess mortality than those diagnosed in winter before adjustment for other variables, but after adjustment the excess mortality ratios were close to unity. Our findings do not support the hypothesis that melanoma cases diagnosed in winter have worse prognosis than cases diagnosed in other seasons. © 2009 UICC     

Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway)

OBJECTIVE: To investigate whether prognosis of breast-, colon- and prostate cancer may be related to vitamin D(3), induced from solar ultra-violet (UV) radiation, through studies on geographical and seasonal variations in UV radiation. METHODS: This study includes 115,096 cases of breast-, colon- or prostate cancer, diagnosed between 1964 and 1992. Among these, 45,667 deaths due to the cancer were registered. On the basis of a north-south gradient in solar UV radiation and geographical climatic differences, Norway was divided into eight residential regions. According to seasonal variations in UV radiation, four periods of diagnosis during the year were used. Case fatality according to residential region and to season of diagnosis was estimated using Cox regression. The effects of occupational sun exposure, childbearing pattern and educational level were also evaluated. RESULTS: No geographic variation in case fatality was observed for the three cancer types studied. A significant variation in prognosis by season of diagnosis was observed. Diagnoses during summer and fall, the seasons with the highest level of vitamin D(3), revealed the lowest risk of cancer death. CONCLUSION: The results suggest that a high level of vitamin D(3) at the time of diagnosis, and thus, during cancer treatment, may improve prognosis of the three cancer types studied.     

Changes in risk of death from breast cancer with season and latitude

The Norwegian counties can conveniently be divided in three groups with different annual UV exposures and different incidence rates of squamous cell carcinoma (SCC) of the skin. In view of the hypothesis that latitude and season of diagnosis may play a role for breast cancer progression, the prognosis of breast cancer as determined for summer and winter diagnosis, were evaluated in the three residential regions. Two age groups were analysed separately (stratification at 50 years). For all regions, and for all ages, the prognosis was best for women diagnosed in the summer season (Relative risk (RR) of death was 15–25% lower for summer diagnosis versus winter diagnosis). There was no significant seasonal variation of the number of new cases. For women diagnosed before the age of 50, a geographical gradient in cancer prognosis was also found (RR of death 0.6, 95% CI: 0.5–0.7 for cases diagnosed in southeast Norway and RR of death 0.8, 95% CI: 0.6–1.1 for diagnosis in the north of Norway). This is in agreement with a 1.5 times larger annual UV exposures and 3–4 times larger incidence rates of SCC in the southeast region when compared with the north region. For women diagnosed after the age of 50, no significant difference was found between the three regions. Despite a 17% higher vitamin D intake from food in north of Norway no difference in cancer survival was found for diagnosis during winter (when no significant differences in the levels of UV exposure can be detected between regions). The overall data support our earlier hypothesis that season of diagnosis and therapy start improves the survival for breast cancer.     

A case–control study of occupational sunlight exposure and renal cancer risk

Epidemiological evidence of a relationship between vitamin D and kidney cancer risk has been inconsistent despite experimental data indicating that vitamin D and its metabolites may inhibit carcinogenesis. Previously we reported an inverse association between renal cell carcinoma (RCC) risk and occupational ultraviolet (UV) exposure among European men. In this study, we examined the association between occupational UV exposure and RCC risk among US residents and investigated whether this association varied by race and sex. Lifetime occupational data for 1,217 RCC cases and 1,235 controls in a population‐based case–control study, conducted from 2002 to 2007, were assessed for occupational UV exposure. We evaluated exposure metrics in quartiles based on control exposure levels and calculated associations between RCC risk and occupational UV exposure using unconditional logistic regression adjusted for sex, race, body mass index, smoking, hypertension, center, education, family history of cancer and dietary vitamin D intake. A general pattern of decreasing RCC risk with increasing UV exposure was observed. Cases had significantly lower cumulative occupational UV exposure than controls (fourth quartile vs. first: odds ratio = 0.74 [95% confidence interval = 0.56–0.99], p‐trend = 0.03). Similar results were observed for other UV exposure metrics. The association with occupational UV exposure was stronger for women than for men, but did not differ by race. Our findings suggest an inverse association between occupational UV exposure and RCC, particularly among women. Given the sex finding discrepancies in this study versus our previous study, additional research is need to clarify whether the protective effects of occupational UV exposure and RCC risk are real.     

Retinoblastoma incidence and sunlight exposure

To evaluate positive findings from an earlier report, we studied the relation between retinoblastoma incidence and ultraviolet (UV-B) radiation levels in the Surveillance, Epidemiology, and End Results (SEER) programme areas of the USA using weighted regression, as well as in international data after adjusting for race, economic development, and climate. The association was not statistically significant within the USA (P > 0.20). At an international level, the relation was significant overall and after adjusting for economic development, but it was not significant after adjusting for race and tropical climate, suggesting that environmental factors other than UV-B may be responsible for the geographic patterns of retinoblastoma.     

Cancer survival in Kampala, Uganda

Epidemiological data on the occurrence of cancer in sub-Saharan Africa are sparse, and population-based cancer survival data are even more difficult to obtain due to various logistic difficulties. The population-based Cancer Registry of Kampala, Uganda, has followed up the vital status of all registered cancer patients with one of the 14 most common forms of cancer, who were diagnosed and registered between 1993 and 1997 in the study area. We report 5-year absolute and relative survival estimates of the Ugandan patients and compare them with those of black American patients diagnosed in the same years and included in the SEER Program of the United States. In general, the prognosis of cancer patients in Uganda was very poor. Differences in survival between the two patient populations were particularly dramatic for those cancer types for which early diagnosis and effective treatment is possible. For example, 5-year relative survival was as low as 8.3% for colorectal cancer and 17.7% for cervical cancer in Uganda, compared with 54.2 and 63.9%, respectively, for black American patients. The collection of good-quality follow-up data was possible in the African environment. The very poor prognosis of Ugandan patients is most likely explained by the lack of access to early diagnosis and treatment options in the country. On the policy level, the results underscore the importance of the consistent application of the national cancer control programme guidelines as outlined by the World Health Organization.     

Prostate cancer diagnosis,staging and survival

Prostate cancer is the most common malignancy in men and the second most common cancer related death. Through research, we have found that African–American men and men with a family history of prostate cancer have a significantly higher risk of prostate cancer. In the 90's the mortality rate from prostate cancer decreased, presumably due to PSA testing. Patients with organ-confined tumors, particularly if they have a moderate Gleason score have an excellent chance of long-term survival with radical prostatectomy or external beam radiation therapy. Advances in detecting micrometastatic disease are needed to further impact on this disease.     

Sun exposure prior to diagnosis is associated with improved survival in melanoma patients: results from a long-term follow-up study of Italian patients

We followed up 260 melanoma patients included in a population-based case–control study in Turin, Italy. We collected information on host factors and sun exposure history, and analysed their relative survival.Intermittent sun exposure was inversely associated with the risk of death (hazard ratios, HR = 0.41 95% confidence interval, CI = 0.17–0.98). Outdoor work was not associated with an increased risk of death. Multivariate models including anatomic site, melanoma thickness and histology, showed that intermittent sun exposure had a tendency to be inversely associated with the risk of death from melanoma with a HR of 0.60 (95%CI = 0.24–1.5) in the patients with 1 to 59 weeks and a HR of 0.54 (95%CI = 0.23–1.2) in patients with more than 60 weeks spent on the beach during their lifetime.This study, with similar methods and a longer follow-up, confirms the finding that sun exposure prior to diagnosis of melanoma is associated with improved survival.     

Decreased cancer survival in individuals separated at time of diagnosis

BACKGROUND:

It long has been recognized that married patients have improved cancer survival when compared with unmarried patients. This has been postulated as being due to increased support, potentially leading to better compliance with therapy. Conversely, some data exist pointing to a relationship between marital discord and decreased immunity. We examined whether unmarried patients have a different prognosis by whether they are 1) never married, 2) divorced, 3) widowed, or 4) separated at time of diagnosis.

METHODS:

The public access data of the Surveillance, Epidemiology and End Results (SEER) registry were queried for cancer survival across all 17 registries between 1973 and 2004. SEER last updated data in April 2007. Records of 3.79 million patients were included in the analysis. We specifically analyzed 5‐year and 10‐year relative survival (RS; 5yRS, 10yRS), defined as observed survival divided by observed survival of an age‐matched, race‐matched, and gender‐matched population without disease, for all cancer patients by marital status, with specific subset analyses as indicated.

RESULTS:

Among unmarried patients, those separated at time of diagnosis had the lowest survival, followed by widowed, divorced, and never married patients. 5‐year and 10‐year RS of separated patients was 72% and 64% than that of married patients, respectively. This relationship persists when data are analyzed by gender.

CONCLUSIONS:

Separated marital status is associated with a significant decrement in cancer survival, even in comparison with other unmarried groups. While other socioeconomic variables could contribute to this phenomenon, further research into the immunologic correlates of the acutely stressful condition of marital separation should be conducted. Cancer 2009. © 2009 American Cancer Society.     

Oxidant-antioxidant status in relation to survival among breast cancer patients.

The role of plasma oxidant-antioxidant status in survival after breast cancer surgery was investigated in a cohort of patients (n = 363) hospitalized in Southern France between 1989 and 1992. The median follow-up was 8 years after surgery for histologically confirmed breast cancer. Plasma analyses were performed after diagnosis and before surgery and adjuvant therapy. We found an inverse relationship between plasma lipoperoxides (MDA) and tumor size at diagnosis, together with higher lipoperoxide levels in node-negative tumors than in node-positive ones (TNM). The longitudinal approach revealed an increased risk of recurrence for patients with plasma lipoperoxides in the highest tertile of the sample (RR = 2.1, 95% CI 1.1-4.0). In addition, the risk of recurrence increased (RR = 1.7, 95%CI 1.0-3.0), after adjustment for the known prognostic factors (TNM), for patients with plasma lipid-adjusted vitamin E levels of over 22 micromol/l. The risk of breast cancer death was twice as great for patients with plasma lipid-adjusted vitamin E levels above this value. Excesses of plasma lipoperoxides and vitamin E appear to be factors in poor prognosis for breast cancer-specific survival (OVS) and disease-free survival (DFS), respectively, independent of tumor characteristics at diagnosis. Several hypotheses are advanced to explain the possible role of plasma vitamin E as a factor in poor prognosis for survival.     

Lack of any Association between Season of Diagnosis and Survival of Gastric Cancer Cases in Kayseri,Turkey

Background: The influence of season of diagnosis on cancer survival has been an interesting issue for manyyears. Most studies have shown a possible association between seasonality and survival in some cancers. Weaimed to investigate whether there is an association between season of diagnosis and survival in patients withgastric cancer. Materials and Methods: We reviewed retrospectively the files of 279 histologically proven gastriccancer patients. According to diagnosis date, the patients were grouped into 4 seasons of diagnosis groups, spring,summer, autumn, and winter. Results: There was no significant differences when the overall survival rates of thepatients were compared according to the patients’ season of diagnosis (p: 0.871). Median overall survival rateswere 22.0 (14.5-29.5) months for the patients who were diagnosed in spring, 24.0 (12.4-35.6) for summer, 18.0(9.96-26.0) for autumn and 21.0 (16.3-25.7) for winter. Median disease-free survival rates were 66.0 (44.1-68.1)months for the patients who were diagnosed in spring, 28.0 (17.0-39.0) for summer, 22.0 (0-46.4) for autumn and23.0 (17.5-28.5) for winter. While the rate was best for the patients diagnosed in spring the differences were notstatistically significant (p= 0.382). Conclusions: On the basis of the above results the season was not suggestedas contributing to prognosis in gastric cancer cases in Kayseri, Turkey.     

Stage at diagnosis is a key explanation of differences in breast cancer survival across Europe

We used multiple regression models to assess the influence of disease stage at diagnosis on the 5‐year relative survival of 4,478 patients diagnosed with breast cancer in 1990–1992. The cases were representative samples from 17 population‐based cancer registries in 6 European countries (Estonia, France, Italy, Netherlands, Spain and UK) that were combined into 9 regional groups based on similar survival. Five‐year relative survival was 79% overall, varying from 98% for early, node‐negative (T1N0M0) tumours; 87% for large, node‐negative (T2‐3N0M0) tumours; 76% for node‐positive (T1‐3N+M0) tumours and 55% for locally advanced (T4NxM0) tumours to 18% for metastatic (M1) tumours and 69% for tumours of unspecified stage. There was considerable variation across Europe in relative survival within each disease stage, but this was least marked for early node‐negative tumours. Overall 5‐year relative survival was highest in the French group of Bas‐Rhin, Côte d'Or, Hérault and Isère (86%), and lowest in Estonia (66%). These geographic groups were characterised by the highest and lowest percentages of women with early stage disease (T1N0M0: 39% and 9%, respectively). The French, Dutch and Italian groups had the highest percentage of operated cases. The number of axillary nodes examined, a factor influencing nodal status, was highest in Italy and Spain. After adjusting for TNM stage and the number of nodes examined, survival differences were greatly reduced, indicating that for these women, diagnosed with breast cancer in Europe during 1990–1992, the survival differences were mainly due to differences in stage at diagnosis. However, in 3 regional groups, the relative risks of death remained high even after these adjustments, suggesting less than optimal treatment. Screening for breast cancer did not seem to affect the survival patterns once stage had been taken into account. © 2003 Wiley‐Liss, Inc.     

Cancer incidence,survival and mortality: Explaining the concepts

Cancer incidence, survival and mortality are essential population‐based indicators for public health and cancer control. Confusion and misunderstanding still surround the estimation and interpretation of these indicators. Recurring controversies over the use and misuse of population‐based cancer statistics in health policy suggests the need for further clarification. In our article, we describe the concepts that underlie the measures of incidence, survival and mortality, and illustrate the synergy between these measures of the cancer burden. We demonstrate the relationships between trends in incidence, survival and mortality, using real data for cancers of the lung and breast from England and Sweden. Finally, we discuss the importance of using all three measures in combination when interpreting overall progress in cancer control, and we offer some recommendations for their use.     

Prospective study of ultraviolet radiation exposure and risk of cancer in the United States

Ecologic studies have reported that solar ultraviolet radiation (UVR) exposure is associated with cancer; however, little evidence is available from prospective studies. We aimed to assess the association between an objective measure of ambient UVR exposure and risk of total and site-specific cancer in a large, regionally diverse cohort [450,934 white, non-Hispanic subjects (50-71 years) in the prospective National Institutes of Health (NIH)-AARP Diet and Health Study] after accounting for individual-level confounding risk factors. Estimated erythemal UVR exposure from satellite Total Ozone Mapping Spectrometer (TOMS) data from NASA was linked to the US Census Bureau 2000 census tract (centroid) of baseline residence for each subject. We used Cox proportional hazards models adjusted for multiple potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of UVR exposure. Restricted cubic splines examined nonlinear relationships. Over 9 years of follow-up, UVR exposure was inversely associated with total cancer risk (N = 75,917; highest versus lowest quartile; HR = 0.97, 95% CI = 0.95-0.99; p-trend < 0.001). In site-specific cancer analyses, UVR exposure was associated with increased melanoma risk (highest versus lowest quartile; HR = 1.22, 95% CI = 1.13-1.32; p-trend < 0.001) and decreased risk of non-Hodgkin's lymphoma (HR = 0.82, 95% CI = 0.74-0.92) and colon (HR = 0.88, 95% CI = 0.82-0.96), squamous cell lung (HR = 0.86, 95% CI = 0.75-0.98), pleural (HR = 0.57, 95% CI = 0.38-0.84), prostate (HR = 0.91, 95% CI = 0.88-0.95), kidney (HR = 0.83, 95% CI = 0.73-0.94) and bladder (HR = 0.88, 95% CI = 0.81-0.96) cancers (all p-trend < 0.05). We also found nonlinear associations for some cancer sites, including the thyroid and pancreas. Our results add to mounting evidence for the influential role of UVR exposure on cancer.     

Associations of circulating 25-hydroxyvitamin D with prostate cancer diagnosis, stage and grade

Epidemiological studies suggest that vitamin D protects against prostate cancer, although evidence is limited and inconsistent. We investigated associations of circulating total 25-hydroxyvitamin D (25(OH)D) with prostate specific antigen-detected prostate cancer in a case-control study nested within the prostate testing for cancer and treatment (ProtecT) trial. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) quantifying the association between circulating total 25(OH)D and prostate cancer. In case-only analyses, we used unconditional logistic regression to quantify associations of total 25(OH)D with stage (advanced vs. localized) and Gleason grade (high-grade (≥7) vs. low-grade (<7)). Predetermined categories of total 25(OH)D were defined as: high: ≥30 ng/mL; adequate: 20-<30 ng/mL; insufficient: 12-<20 ng/mL; deficient: <12 ng/mL. Fractional polynomials were used to investigate the existence of any U-shaped relationship. We included 1,447 prostate cancer cases (153 advanced, 469 high-grade) and 1,449 healthy controls. There was evidence that men deficient in vitamin D had a 2-fold increased risk of advanced versus localized cancer (OR for deficient vs. adequate total 25(OH)D=2.33, 95% CI: 1.26, 4.28) and high-grade versus low-grade cancer (OR for deficient vs. adequate total 25(OH)D=1.78, 95% CI: 1.15, 2.77). There was no evidence of a linear association between total 25(OH)D and prostate cancer (p=0.44) or of an increased risk of prostate cancer with high and low vitamin D levels. Our study provides evidence that lower 25(OH)D concentrations were associated with more aggressive cancers (advanced versus localized cancers and high- versus low-Gleason grade), but there was no evidence of an association with overall prostate cancer risk.     

25‐Hydroxyvitamin D2/D3 levels and factors associated with systemic inflammation and melanoma survival in the Leeds Melanoma Cohort

Lower 25‐hydroxyvitamin D₂/D₃ levels at melanoma diagnosis are associated with thicker primaries and poorer survival. We postulated that this might relate to the deleterious effect of systemic inflammation as 25‐hydroxyvitamin D₂/D₃ levels are inversely associated with levels of C‐reactive protein. 2,182 participants in the Leeds Melanoma Cohort (median follow‐up 7.98 years) provided data on drug exposure, comorbidities and a serum 25‐hydroxyvitamin D₂/D₃ level at recruitment. Factors reported to modify systemic inflammation (low vitamin D levels, high body mass index, use of aspirin or nonsteroidal anti‐inflammatory drugs or smoking were tested as predictors of microscopic ulceration (in which primary tumors are inflamed) and melanoma‐specific survival (MSS). Ulceration was independently associated with lower 25‐hydroxyvitamin D₂/D₃ levels (odds ratio (OR) = 0.94 per 10 nmol/L, 95% CI 0.88–1.00, p = 0.05) and smoking at diagnosis (OR = 1.47, 95% CI 1.00–2.15, p = 0.04). In analyses adjusted for age and sex, a protective effect was seen of 25‐hydroxyvitamin D₂/D₃ levels at diagnosis on melanoma death (OR = 0.89 per 10 nmol/L, 95% CI 0.83–0.95, p < 0.001) and smoking increased the risk of death (OR = 1.13 per 10 years, 95% CI 1.05–1.22, p = 0.001). In multivariable analyses (adjusted for tumor thickness) the associations with death from melanoma were low 25‐hydroxyvitamin D₂/D₃ level at recruitment (<20 nmol/L vs. 20–60 nmol/L, hazard ratio (HR) = 1.52, 95% CI 0.97–2.40, p = 0.07) and smoking duration at diagnosis (HR = 1.11, 95% CI 1.03–1.20, p = 0.009). The study shows evidence that lower vitamin D levels and smoking are associated with ulceration of primary melanomas and poorer MSS. Further analyses are necessary to understand any biological mechanisms that underlie these findings.