Incidence Of Melanoma Research Articles

Translated article] Dermoscopic Changes in Melanocytic Lesions in 368 Patients With Atypical Nevus Syndrome and Their Association With Melanoma Incidence: A Cohort Study

Background and objectiveAtypical nevus syndrome has been described as one of the main risk factors for melanoma. The aim of this study was to analyze dermoscopic changes observed in melanocytic lesions over a follow-up period of 5 years in patients with atypical nevus syndrome. Material and methodsWe conducted a retrospective follow-up study of a cohort of patients seen at a specialized skin cancer and digital body mapping clinic in Medellin, Colombia, between January 2017 and December 2022. We analyzed the dermoscopic changes observed during this period and explored their association with newly diagnosed melanoma. ResultsA total of 368 patients (187 women) with a median (interquartile range) age of 43 (37-51) years were included. The dermoscopic features observed at 5 years were an atypical network (222 patients, 60.3%), asymmetric globules (163, 44.2%), white-gray regression areas (105, 28.5%), lesion regression (72, 19.5%), a negative pigment network (59, 16%), asymmetric eccentric pigmentation (28, 7.6%), asymmetric projections (21, 5.7%), and asymmetric vascular patterns (8, 2.1%). Melanoma was diagnosed in 12.2% of patients during follow-up. Features significantly associated with a shorter time to melanoma onset were grayish-white areas (P<.001), asymmetric globules (P=.011), asymmetric eccentric pigmentation (P=.047), and a negative pigment network (P=.001). ConclusionsThe main dermoscopic features of melanocytic lesions in patients with atypical nevus syndrome associated with progression to melanoma were grayish-white areas, asymmetric globules, asymmetric spots, and a negative pigment network.

Association of early-stage incidence and mortality in malignant melanoma - a population-based ecological study.

Germany-wide skin cancer screening was introduced in 2008 to reduce skin cancer mortality and morbidity. However, the effectiveness of the program is still unclear. We explore the relationship between early-stage melanoma incidence and melanoma mortality in subsequent years, using early-stage melanoma incidence as surrogate for screening participation and early detection. Data on melanoma incidence for 2005-2016 and melanoma mortality for 2005-2018 were obtained for 244 German counties. We investigated the correlation between several measures of incidence and mortality with correlation analyses and linear regressions. Melanoma incidence of early stages (in situ and T1) rose by 69% between pre-screening (2005-2007) and screening period (2008-2010). In contrast, there was no temporal trend in mortality over time. Correlation coefficients between incidence and mortality variables ranged between -0.14 and 0.10 (not significant). Linear regression indicated that mortality 6years after screening introduction decreases with increasing change in early-stage incidence (b=-0.0029, 95% confidence interval [-0.0066, 0.0007]). The estimated population-based effects of skin cancer screening on melanoma mortality were minimal and not significant. A potential effectiveness cannot be demonstrated.

Abstract PR010: Cutaneous melanoma treatment outcomes in Texas: A study of the Texas Cancer Registry/Medicare linked database and an analysis of disparities

Abstract Background: Given that Hispanics make up a large portion of the United States, further research has been necessary to analyze the effects of treatment methods on all-cause and skin cancer mortality in Hispanic populations. While Caucasians have the highest incidence of melanoma, Hispanics make up the second most common group in the United States and in Texas. Incidence of melanoma is increasing, including in the Hispanic population. Importantly, mortality from melanoma is higher in the Hispanic than in the Caucasian population. Methods: We conducted an analysis of patients with cutaneous melanoma in the Texas Cancer Registry Medicare database to assess treatment modalities used and outcomes among demographic groups from 2007 to 2018. A bivariate analysis using Chi-square, Fisher’s exact test, and Student’s T-Test was done to compare patient, clinical, cancer and treatment characteristics between Hispanic and Non-Hispanic White (NHW). A Cox Proportional Hazard regression analysis was performed to assess treatment effect on outcome, with race-ethnicity as an effector modifier. Models were adjusted for patient age, sex, cancer stage, primary care provider, and comorbidity. Results: A higher percentage of Hispanic patients (7.6%) presented with a metastatic tumor stage diagnosis and cancer-related mortality (22.11%) compared to NHW patients (p &amp;lt;0 .0001). In both the Hispanic and NHW cohorts, post-diagnosis radiation (Hispanic 95% CI 0.984 – 2.634, NHW 95% CI 2.082-2.648) and post-diagnosis chemotherapy (Hispanic 95% CI 1.085-3.321, NHW 95% CI 1.664-2.489) are each associated with an increased risk in cancer-related mortality. Similar results are seen with post-diagnosis radiation (Hispanic 95% CI 1.121-2.40, NHW 95% CI 1.644-1.971) and chemotherapy (Hispanic 95% CI 0.900-2.368, NHW 95% CI 1.356-1.869) when considering all-cause mortality in both populations. However, post-diagnosis surgery (95% CI 0.571-0.678) and post-diagnosis immunotherapy (95% CI 0.032-1.565) had the opposite effect in cancer-related mortality for NHW. Cancer-related mortality for post-diagnosis surgery in the Hispanic cohort had a similar trend (95% CI 0.395-0.856), yet the effect of post-diagnosis immunotherapy was dismissed due to small sample size. Conclusion: Our results propose differences in all-cause and cancer-only related mortality with separate treatment modalities, particularly with chemotherapy and radiation therapy; this retrospective cohort study validated that health disparities exist in the Hispanic Medicare population of Texas with cutaneous melanoma. Citation Format: Hannah R. Riva, Fabiola Ramirez, Lorena Fernandez, Yae Kye, David Lopez, Biai Digbeu, Jessica Chacon. Cutaneous melanoma treatment outcomes in Texas: A study of the Texas Cancer Registry/Medicare linked database and an analysis of disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr PR010.

Abstract A009: Engaging Latino communities to develop a skin cancer intervention: A qualitative exploration

Abstract Introduction: In the past two decades, melanoma (the deadliest form of skin cancer) incidence among Latinos has risen by 20%. Despite the lower incidence rate of skin cancers among Latinos compared to Caucasians, the mortality rate of Latinos is higher. However, skin cancer is understudied among Latinos and they were less likely to engage in skin cancer preventive behaviors. This qualitative study explored Latinos’ beliefs and behaviors related to skin cancer and their interest in a skin cancer intervention from both community members and key stakeholders. Methods: Latinos were recruited in New Jersey through community organizations and social media posts (n=34; 11 Spanish-preferring and 23 English-preferring) for focus group discussions. Five focus groups (2 in Spanish and 3 in English) were conducted, where participants discussed their perceptions and behaviors about skin cancer, sun protection, skin self-examination, culture and lifestyles, and their recommendations for a mobile skin cancer intervention. Additionally, healthcare providers (n=4) and Latino community leaders (n=5) were recruited for individual interviews to complement the results of focus groups. A thematic analysis was conducted on all transcripts. Results: Focus group participants aged from 18 to 73 (M=33.44), 50% were female (n=17), 29.4% (n=10) had a household income below $25000, and 32.3% (n=11) had less than a college degree. Awareness of and knowledge about skin cancer, sun protection, and skin examination were low overall. All participants indicated that skin cancer communication is rare among Latinos. There was consensus among the findings of the focus groups and key stakeholder interviews. Perceived barriers included: 1) limited access (e.g., health insurance); 2) low awareness or knowledge (e.g., don’t know efficient sun protection methods or what to look for in skin self-examination); 3) misperception (e.g., dark skin won’t get skin cancer). Salient facilitators included: 1) care for family (e.g., sunscreen for children and parents); 2) consequences (e.g., worry and fear of aging or death, sunburns); 3) coverage or access (e.g., good insurance). Social media usage was prevalent in many households, with WhatsApp and Facebook being popular platforms for communication with family and friends, as well as for discussing health-related topics. The consensus regarding intervention messages was that visuals and clear/simple messages featuring Latinos would be effective in educating about skin cancer and promoting behavior change. As complementary findings, key stakeholders indicated that educating the women in the family on sun safety behaviors, involving local Latino organizations, and delivering messages from physicians directly would be effective. Conclusions: Findings highlight the importance of skin cancer education within the Latino community, particularly due to low awareness and misperception of skin cancer, sun protection, and skin examination. Social media present a promising way to reach Latinos through culturally-centered and mobile-based interventions. Citation Format: Zhaomeng Niu, Aarthi Shanmugavel, Yonaira Rivera, Carolina Lozada, Emily Peters, Carolyn Heckman. Engaging Latino communities to develop a skin cancer intervention: A qualitative exploration [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A009.

Increased Incidence of Melanoma, Prostate, Lung, Bladder, Renal and Thyroid Cancer after Diagnosis of Primary Cutaneous B-Cell Lymphoma: A SEER Database Analysis

Background: Primary cutaneous B-cell lymphomas (PCBCLs) are a subset of non-Hodgkin lymphomas originating in the skin. The risk of developing other malignancies in PCBCL patients is not known. We evaluated the risk of developing a second primary malignancy after a PCBCL diagnosis. Methods: We utilized the surveillance, epidemiology, and end results (SEER-17) data registry of 9,208,295 patients from 2000-2020 to generate a cohort of 5,435 patients with PCBCL to identify patients at risk for a second primary malignancy. Relative risk was calculated by using the Standardized Incidence Ratio (SIR), defined as the ratio between observed cases (O) and expected cases (E) of malignancies (SIR = O/E). Statistical significance was established based on 95% confidence intervals (CI). Results: Of the 5,435 patients with PCBCL, 847 (16%) received diagnoses of a second malignancy, identifying a higher risk than the general population (SIR, 1.54; 95% CI, 1.43-1.64). Males had a higher chance of developing prostate cancer (SIR, 1.29; 95% CI, 1.07-1.54), melanoma (SIR, 1.49; 95% CI, 1.03-2.09), and bladder cancer (SIR, 1.42; 95% CI, 1.01-1.94). Females were more predisposed to cancers of the lung (SIR, 1.69; 95% CI, 1.25-2.24), thyroid (SIR, 3.06; 95% CI, 1.63-5.23), and kidney (SIR, 2.13; 95% CI 1.06-3.81). For males with PCBCL, there was an increased risk of prostate cancer in patients 60-69 (SIR, 1.53; 95% CI, 1.14-2.02). For females, there was an increased risk of lung cancer in patients over 70, especially in the age group of 70-79 (SIR, 1.84; 95% CI, 1.12-2.84). For cutaneous melanoma, bladder, renal, and thyroid cancer, there was no age group identified to be at a significantly greater risk. Prostate cancer risk was increased within the first year (SIR, 2.09; 95% CI, (1.28 - 3.23) and between 5-10 years after PCBCL diagnosis (SIR, 1.45; 95% CI, 1.04-1.97) .For males, melanoma and bladder cancer were associated with an increased risk between 1-5 years after PCBCL (SIR, 1.91; 95% CI, 1.09-3.11 and SIR, 1.7; 95% CI, 1.01-2.68). Females were at the highest risk of developing thyroid cancer within the first year of PCBCL diagnosis (SIR, 21.11; 95% CI, 10.12-38.83) and lung cancer 1-5 years after PCBCL diagnosis (SIR, 1.7; 95% CI, 1.04-2.62). For renal cancer, there was no latency identified carrying an increased risk. Conclusion: These data, should inform screening strategies for melanoma, prostate, bladder, lung, renal, and thyroid cancer in patients with PCBCL. Males 60-69 within 10 years of PCBCL can benefit from prostate screening. Males within 1-5 years of PCBCL diagnosis can benefit from screening for melanoma and bladder cancer. Females can benefit from thyroid, lung, and renal cancer surveillance. Specifically for females over 70, screening for lung cancer should be considered, and for females within the first year of PCBCL diagnosis, thyroid cancer screening should be considered.

Educational Intervention and Melanoma Prognosis in Black People.

A systematic search was conducted on the PubMed database using the keywords "education," "melanoma," and "African Americans." The results were filtered to include studies published within the last decade that focused on melanoma diagnosis, risk, or outcomes. These selected studies included African Americans, non-Hispanic Black individuals, or those with darker skin tones and compared them with educational interventions or non-Hispanic White groups. The studies showedan overall positive impact of targeted educational initiatives on using sun-protective behaviors, health education, and self-efficacy related to melanoma. Notably, interventions proven to be effective for non-Hispanic White populations also demonstrated efficacy in other racial groups, including non-Hispanic Blacks. It was observed that non-Hispanic Blacks exhibited an overall reduced level of concern regarding melanoma, partly due to its lower incidence within this demographic.Furthermore, these studies focussed on the disparities in melanoma incidence and survival rates among different racial groups. Non-Hispanic Black individuals were found to have a higher incidence of melanoma and lower survival rates compared to non-Hispanic White individuals. Collectively, the studies evaluating melanoma educational interventions for darker skin tones yield promising results for improving melanoma prognosis in Black communities. They underscore the importance of addressing racial disparities in melanoma awareness, diagnosis, and treatments. These studies also highlighted the barriers to sun protection behaviors, such as cost, limited awareness, and misconceptions, particularly prevalent among ethnic communities and youth. The use of melanoma photographs specifically tailored to darker skin tones in outreach efforts to enhance identification, self-examination, and early detection should be considered to improve melanoma prognosis similar to the non-White population.

Determining the core content of a digital survivorship care plan for melanoma survivors: a multistakeholder Delphi consensus study.

Increasing melanoma incidence and improved survival emphasize the importance of survivorship care plans (SCPs). We conducted a multistakeholder Delphi study to achieve consensus on core melanoma SCP content. Of the 44 potential elements, 24 (55%) reached consensus for inclusion. Notably, melanoma survivors and healthcare providers differed in their preferences, with survivors prioritizing coordination improvements and healthcare providers emphasizing psychosocial care. Exploring and overcoming these differences in opinions and including the consented elements as a basis in the design of the SCP can facilitate its implementation in practice and lead to survivorship care tailored to stakeholders’ needs.

Artificial Intelligence Algorithms for Benign vs. Malignant Dermoscopic Skin Lesion Image Classification.

In recent decades, the incidence of melanoma has grown rapidly. Hence, early diagnosis is crucial to improving clinical outcomes. Here, we propose and compare a classical image analysis-based machine learning method with a deep learning one to automatically classify benign vs. malignant dermoscopic skin lesion images. The same dataset of 25,122 publicly available dermoscopic images was used to train both models, while a disjointed test set of 200 images was used for the evaluation phase. The training dataset was randomly divided into 10 datasets of 19,932 images to obtain an equal distribution between the two classes. By testing both models on the disjoint set, the deep learning-based method returned accuracy of 85.4 ± 3.2% and specificity of 75.5 ± 7.6%, while the machine learning one showed accuracy and specificity of 73.8 ± 1.1% and 44.5 ± 4.7%, respectively. Although both approaches performed well in the validation phase, the convolutional neural network outperformed the ensemble boosted tree classifier on the disjoint test set, showing better generalization ability. The integration of new melanoma detection algorithms with digital dermoscopic devices could enable a faster screening of the population, improve patient management, and achieve better survival rates.

IMMU-02. IS DUAL AGENT IMMUNOTHERAPY SHIFTING THE EPIDEMIOLOGY OF MELANOMA BRAIN METASTASES? A REAL-WORLD ANALYSIS AND SINGLE-INSTITUTION VALIDATION

Abstract INTRODUCTION Dual agent immunotherapy (dIT) has been paradigm changing in melanoma brain metastasis (MBM). Recent clinical trials have supported the role of dIT for upfront management of small, asymptomatic MBM. Yet, its potential role in extending brain metastasis free survival and decreasing MBM incidence overall has been inadequately explored. Objective: To compare new brain metastasis incidence, median overall survival (OS), and brain metastasis free survival (BMFS) in melanoma patients treated with dIT versus single immunotherapy (sIT). METHODS A real-world deidentified database collating clinical information from 92 organizations (TriNetX, Inc) was queried. Melanoma patients without brain metastases prior to immunotherapy were stratified by treatment (anti-CTLA4 [sIT] and combination anti-CTLA4/ anti-PD1 [dIT]) and propensity score matched. A complementary single-institution retrospective cohort study analyzed melanoma patients treated from 2012-2019. The incidence of new asynchronous MBMs after immunotherapy initiation was compared. Median OS and BMFS were compared via log-rank tests and Cox proportional-hazards model. RESULTS TriNetX identified 8,686 melanoma patients who received immunotherapy (4,585 dIT; 4,101 sIT). MBM prevalence was 9.6%, and 15.6%, for the dIT and sIT cohorts, respectively (p &amp;lt; 0.0001). DIT was associated with a lower likelihood of developing MBM compared to sIT (OR [95%CI], 0.64 [0.61-0.77]). After propensity score matching on demographics and significant comorbidities, OS was not statistically different between treatment groups. On single-institution analysis, 222 melanoma patients were included (89 dIT; 45 anti-CTLA4; 88 anti-PD1). Patients were predominantly stage III at diagnosis (43%) with PD-L1 expression (51%) and BRAF (43%), and NRAS wildtype (50%) mutational status. BMFS was significantly extended in the dIT cohort compared to the anti-CTLA4 or anti-PD1 alone cohorts (406, 217, 139 days, respectively; p&amp;lt; 0.0001). On Cox-proportional hazards model, no covariates significantly contributed to the BMFS difference. CONCLUSION These data highlight the impact of combination anti-CTL4/ anti-PD1 immunotherapy in decreasing BM incidence in melanoma.

Melanoma incidence and mortality: Exploring the impact of regional ultraviolet (UV) radiation and socioeconomic status in the context of Breslow thickness

Melanoma incidence and mortality: Exploring the impact of regional ultraviolet (UV) radiation and socioeconomic status in the context of Breslow thickness

Prognosis of CDKN2A germline mutation in patients with familial melanoma: a systematic review and meta-analysis.

Familial melanoma is defined as melanoma occurring in two or more first-degree relatives by the WHO. Germline mutations are isolated in a subset of them. It is well known that CDKN2A is the most frequently mutated high-risk gene in familial melanoma, however, the prognosis it confers to patients who carry its mutations is still controversial. This review aims to assess whether germline mutations imply a worse prognosis in patients with familial melanoma. A systematic review and meta-analysis were conducted by searching the electronic databases PubMed/MEDLINE, EMBASE, and Cochrane Library. Data from 3 independent populations were eventually included in the meta-analysis, involving 291 cases and 57 416 controls. The results of this systematic review and meta-analysis suggest that there is a tendency for patients with germline mutations in the CDKN2A gene to have a worse overall survival (HR = 1.30, 95% CI = 0.99-1.69, P = 0.05) and melanoma-specific survival (HR = 1.5, 95% CI = 0.97-2.31, P = 0.07). Carrier patients would not only have more incidence of melanoma and a higher risk of a second melanoma, but they also seem to have a worse prognosis. The inclusion of gene panel testing in clinical practice and the collaboration within consortia are needed to provide further evidence on the prognosis of these patients.

Melanoma-the therapeutic considerations in the clinical practice.

The incidence of melanoma is increasing and prolonged exposure to ultraviolet (UV) radiation remains the main risk factor. Public health measures have been vital in tackling the increased incidence and prevalence of melanoma. The management of melanoma has been revolutionised with the approval of new immunotherapy treatments (anti PD-1, CTLA-4 and LAG-3 antibodies) and targeted therapies (BRAF and MEK inhibitors). With some of these therapies becoming the standard of care in the management of advanced disease, it is likely we will see their use increase in the adjuvant and neoadjuvant setting. Recently, literature has demonstrated the benefits patients could derive from the combination of immune checkpoint inhibitors (ICIs) due to the promising results on its efficacy when compared to monotherapy. However, greater clarity on its use is needed in more unique presentations such as BRAF-wild type melanoma, where the lack of driver mutations makes disease management more challenging. Surgical resection remains an integral part of the management of earlier stages of the disease with a consequent decrease in reliance on other forms of therapy such as chemotherapy and radiotherapy. Finally, we evaluated the novel emerging experimental approaches to treatment such as adoptive T cell therapy, novel oncolytic treatments and cancer vaccines. We discussed how their use could improve patients' prognosis, enhance treatment efficacy, and potentially achieve cure.

Dipeptidyl peptidase-4 inhibitors and the risk of skin cancer among patients with type 2 diabetes: a UK population-based cohort study

IntroductionThe dipeptidyl peptidase-4 (DPP-4) enzyme significantly influences carcinogenic pathways in the skin. The objective of this study was to determine whether DPP-4 inhibitors are associated with the incidence of melanoma...

Incidence and Mortality of Conjunctival Melanoma in Australia (1982 to 2014).

The purpose of this study was to estimate the incidence and mortality of conjunctival melanoma in Australia from 1982 to 2014. De-identified unit data for all cases of ocular melanoma were extracted from the Australian Cancer Database from 1982 to 2014. Conjunctival melanoma cases were extracted, and the incidence and mortality were analyzed. Incidence rates were age-standardized against the 2001 Australian Standard Population. Mortality was assessed using log-rank and Cox regression. From 1982 to 2014, there were 299 cases of conjunctival melanoma. The age-standardized incidence rate was 0.48 (95% confidence interval [CI] = 0.41 to 0.54) per million per year. Women (0.52, 95% CI = 0.42 to 0.62) had a higher incidence than men (0.42, 95% CI = 0.33 to 0.51). The incidence of conjunctival melanoma increased in men (+1.46%) and significantly women (+1.41%, P = 0.023) over the study period. The mean 5-, 10-, and 15-year disease-specific survival were 90%, 82%, and 80%, respectively, during the 33-year interval. Comparisons of survival among age, sex, and state revealed no significant differences when tested using log-rank or Cox regression. In conclusion, we found an increase in the rate of conjunctival melanoma diagnoses in Australia from 1982 to 2014. Over the same period, disease survival remained unchanged at a mean of 90%.

Patterns of Recurrence of Cutaneous Melanoma: A Literature Review.

The incidence of melanoma has been dramatically increasing over the last decades. Melanoma is considered to have a high metastatic potential and it can progress via lymphatic vessels or through hematogenous metastasis. Different patterns of recurrence have been described, namely, local, satellite, and in transit metastasis (LCIT), lymphatic metastasis, and systemic metastasis. With a more advanced melanoma stage at diagnosis, there is a higher risk for systemic metastasis in comparison to LCIT; in contrast, early-stage melanoma tends to recur more frequently as LCIT and less commonly as systematic metastasis. The aim of this review was to summarize the patterns of recurrence of cuta-neous melanoma, giving the clinician a practical summary for diagnosis, prognosis, and surveillance. There is a knowledge gap of the common patterns of recurrence that needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies as well as patient counseling.

Human CD79b+ neutrophils in the blood are associated with early-stage melanoma.

Due to their abundance in the blood, low RNA content, and short lifespan, neutrophils have been classically considered to be one homogenous pool. However, recent work has found that mature neutrophils and neutrophil progenitors are composed of unique subsets exhibiting context-dependent functions. In this study, we ask if neutrophil heterogeneity is associated with melanoma incidence and/or disease stage. Using mass cytometry, we profiled melanoma patient blood for unique cell surface markers among neutrophils. Markers were tested for their predictiveness using flow cytometry data and random forest machine learning. We identified CD79b+ neutrophils (CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+) that are normally restricted to the bone marrow in healthy humans but appear in the blood of subjects with early-stage melanoma. Further, we found CD79b+ neutrophils present in tumors of subjects with head and neck cancer. AI-mediated machine learning analysis of neutrophils from subjects with melanoma confirmed that CD79b expression among peripheral blood neutrophils is highly important in identifying melanoma incidence. We noted that CD79b+ neutrophils possessed a neutrophilic appearance but have transcriptional and surface-marker phenotypes reminiscent of B cells. Compared to remaining blood neutrophils, CD79b+ neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis. Our work suggests that CD79b+ neutrophils are associated with early-stage melanoma.

Worldwide Incidence of Ocular Melanoma and Correlation With Pigmentation-Related Risk Factors.

The worldwide incidence of ocular melanoma (OM), uveal melanoma (UM), and conjunctival melanoma has last been reported on 15years ago. Recently, light iris color and four specific single-nucleotide-polymorphisms (SNPs) have been identified as a UM-risk factor. Furthermore, six iris color predicting SNPs have been discovered (IrisPlex). Interestingly, two of these (rs129138329 and rs12203592) are also UM-risk factors. We collected worldwide incidence data of OM and investigated its correlations with iris color, IrisPlex SNPs, and UM-risk SNPs. Cases of OM, as defined by the International Classification of Diseases Oncology C69 (eye), 8720/3 to 8790/3 (malignant melanoma), and 8000 to 8005 (malignant neoplasm), between 1988 and 2012, were extracted from the Cancer Incidence in Five Continents. Incidence rates were age-standardized and their trends were analyzed with joinpoint regression and age period cohort modeling. Frequencies for each country of iris color, IrisPlex SNPs, and UM-risk SNPs were collected from the literature. Incidence rates were generally ≥8.0 cases per million person-years in Northern Europe, Western Europe, and Oceania; 2.0 to 7.9 in North America, Eastern Europe, and Southern Europe; and <2.0 in South America, Asia, and Africa. OM incidence correlated with latitude (r = 0.77, P ≤ 0.001) and is expressed as a north-to-south decreasing gradient in Europe. SNP rs12913832 correlated with OM incidence (r = 0.83, P ≤ 0.001), blue iris color (r = 0.56, P ≤ 0.05), green iris color (r = 0.51, P ≤ 0.05), and brown iris color (r = -0.64, P ≤ 0.01). Trends were stable for most countries (28/35). OM incidence is highest in populations of European ancestry and lowest in populations of Asian and African ancestry. Overall, trends are stable, and the spatial correlation among OM incidence, iris color, and rs12913832 may support the role of pigmentation-related risk factors in OM development.

International patterns and trends in the incidence of melanoma and cutaneous squamous cell carcinoma, 1989-2020.

Cutaneous squamous cell carcinoma (cSCC) and melanoma have different associations with sun exposure. To compare trends in the incidence rates of cSCC and melanoma, to provide insight into changing patterns of exposure to ultraviolet radiation (UVR). We compared trends in the incidence of cSCC and melanoma in seven susceptible populations residing at mid-to-high latitudes: Finland, Norway, Sweden, Denmark, Scotland, the Netherlands and Tasmania (Australia). We fitted Joinpoint models to describe trends in age-standardized incidence rates for melanoma and cSCC and calculated the average annual percentage rate of change for the period 1989-2020 (1989-2018 for Tasmania). We calculated the incident rate ratio (IRR) as the ratio of the age-standardized rates (European Standard Population) for cSCC to melanoma and conducted age-period-cohort modelling to compare age, period and cohort effects. The ratio of cSCC-to-melanoma incidence increased with proximity to the equator and over time. In the most recent time period, the incidence of cSCC was higher than the incidence of melanoma for men and women in all seven populations. While the ratio of cSCC-to-melanoma incidence was higher for men vs. women, in most countries the cSCC-to-melanoma IRR increased over time to a greater extent in women than in men. Melanoma incidence was higher among younger people and cSCC incidence was higher among older people; the age at which the incidence of cSCC overtook the incidence of melanoma was progressively younger with proximity to the equator. Despite concerted international efforts to preserve the ozone layer over the past four decades resulting in significant reductions in surface ultraviolet B at mid-latitudes, the incidence of skin cancer, particularly cSCC, continues to rise in those regions. Our findings are consistent with a stronger association with age-associated cumulative sun exposure for cSCC vs. melanoma and suggest that women are currently receiving greater UV radiation exposure than in the past.

Survival in patients diagnosed with melanoma in situ compared to the general population. A Swedish population-based matched cohort study

The incidence of melanoma in situ (MIS) is increasing even more rapidly than the incidence of cutaneous malignant melanoma (CMM). No previous studies have in detail investigated the survival in individuals diagnosed with MIS compared to the general population. This population-based study included individuals with MIS diagnosed in Sweden between 2001 and 2010 and randomly selected MIS-free comparators matched on age, sex and county of residence. Exclusion criterion was a previous CMM. Data on socioeconomic status (SES) including educational level, income and marital status, comorbidity and cause of death were obtained from population-based registers. Overall survival (OS) was estimated by the Kaplan-Meier method. The mortality risk adjusted for SES and comorbidity was assessed by multivariable Cox regression analyses. The survival analyses included 7963 cases and 39,662 comparators. Median age at MIS diagnosis were 63 (IQR 50-75) and 67 (IQR 57-76) years in women and men respectively. Median follow-up time was 120 months (IQR 102-152 months). In individuals with MIS, the ten-year OS was 77% (95% CI 0.76-0.78) compared to 72% (95% CI 0.72-0.73) in comparators. The MIS patients had a higher SES and lower comorbidity burden than the comparators. In a fully adjusted multivariable analysis, including 7772 cases and 38,103 comparators, the mortality was significantly lower in women with MIS (HR 0.88, 95% CI 0.82-0.94) compared to the background population. The corresponding estimate in men was HR 0.94 (95% CI 0.88-1.0). The risk of melanoma-related deaths during the study period was ten-fold higher in MIS patients. Despite being at increased risk of developing CMM, MIS patients had a better OS compared to their matched comparators from the background population, findings which could not fully be explained by differences in SES and comorbidity. Our results are reassuring and should be communicated to patients who have been diagnosed with MIS. Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond, Mats and Stefan Paulsson Trust, Medicon Village, Lund and Uppsala University Hospital (ALF).

IMPACT OF CHLORIDE AND LEAD ION CONTENT IN OPEN WATER SOURCES IN KYZYLORDA REGION ON POPULATION’S CANCER INCIDENCE

Relevance: In 2004-2013, the cumulative cancer incidence was about 200 cases per 100 thousand in Kazakhstan, while in the disaster area of Aral Sea – about 225 cases per 100 thousand. For comparison, cancer incidence in the prosperous region of Karaganda was 140 cases per 100,000 population. As of 2021, the incidence of colorectal cancer in Kyzylorda was 17.73 compared to 5.81 per 100,000 population in 2015.&#x0D; Factors of the surrounding macro- and microenvironment are trigger factors for tumor initiation. Salt deposits of the dried Aral Sea in the form of solonchaks spread to the territory of the entire Kyzylorda region. Pesticides and process water have been discharged into rivers for many years, which has led to the accumulation of heavy metal salts in water and soil on the banks of the rivers and in the place of the dried-up Aral Sea, which in turn can affect the increase in cancer incidence.&#x0D; The study aimed to study the dependence of cancer incidence on water pollution by ions of chlorine and lead in open water bodies in the Kyzylorda region.&#x0D; Methods: Analysis of cancer incidence in 2021 by localization: intestines, stomach, sarcomas, lungs, and melanomas in the Kyzylorda region. Determination of the content of chlorine ions by titration with silver nitrate, spectrophotometric determination of lead ions in the open water sources. Comparative correlation analysis of the concentration of chlorine ions and lead with cancer incidence in this region.&#x0D; Results: The maximum permissible chlorine and lead ions concentrations in all studied open water sources of the Kyzylorda region exceeded the norm by 1.024-20.26 times and 1.4-14.1 times, respectively. The presence of chlorides in the water increased intestine cancer incidence by 17% with an approximation certainty of 0.38. The presence of lead in water increased the incidence of melanomas by 22%, with an approximation certainty of 0.79. The correlation coefficient was r=0.618; p=0.07 for exceeding chlorides’ MPC and bowel cancer incidence.&#x0D; Conclusion: Heavy metals like lead in water samples in regions with increased cancer incidence indicate a co-dependent relationship of these factors. Pollutants such as chlorides and lead increase intestine cancer and melanoma incidence.