Relative Risk Of Melanoma Research Articles

Spain's Rising Melanoma Threat: A Comprehensive 30-Year Analysis (1990-2019).

This study aims to elucidate the factors driving melanoma incidence trends in Spain by analyzing the GBD-2019 dataset (1990-2019) and investigating the age-specific, birth cohort, and period effects on incidence rates. This study analyzed melanoma incidence trends in Spain from 1990 to 2019 using an ecological design. Data were sourced from the Global Burden of Disease Study 2019 and Spain's National Statistics Institute. Age-standardized incidence rates (ASIRs) were calculated using joinpoint regression analysis, and age-period-cohort (A-P-C) modeling was employed to assess the effects of age, time period, and birth cohort on incidence rates. Between 1990 and 2019, an estimated 147,823 melanoma cases were diagnosed in Spain. The ASIRs showed a steady increase for both sexes, with slightly higher rates observed in men. Both men (average annual percentage change (AAPC): 2.8%) and women (AAPC: 2.4%) showed a steady increase in the ASIR over the period. Joinpoint analysis revealed distinct periods of incidence rate changes, with significant upward trends in earlier years followed by stabilization in recent years. Incidence rates increased steadily with age, with the highest rates in the 80-84 age group. Women tended to have slightly higher rates in younger age groups, while men had higher rates in older age groups. Both men and women experienced a steady increase in relative risk of melanoma throughout the 30-year study period, with significant upward trends across birth cohorts. Despite limitations, this study provides valuable insights into factors influencing melanoma incidence in Spain. By understanding age, period, and cohort effects, effective prevention strategies can be developed to reduce melanoma incidence.

Dietary cadmium intake and risk of cutaneous melanoma: An Italian population-based case-control study

IntroductionExposure to the heavy metal cadmium has been associated with many adverse health effects, such as atherosclerosis, diabetes, and cancer, possibly melanoma. In non-occupationally exposed individuals, food intake is a major source of cadmium exposure, after smoking. We aimed to assess the risk of melanoma in relation to dietary cadmium intake. MethodsUsing a population-based case-control study design, we recruited 380 incident cases of newly-diagnosed cutaneous melanoma and 719 matched controls in the Emilia-Romagna Region, Northern Italy in the years 2005-2006. We evaluated dietary intake using a semi-quantitative food frequency questionnaire. We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) for melanoma according to quintiles of dietary cadmium intake, adjusting for several potential confounders, and we modeled the association non-parametrically, using restricted cubic splines. ResultsMedian energy-adjusted intake of cadmium was 6.11 μg/day (interquartile range 5.38–6.91) among cases and 5.97 μg/day (5.15–6.79) among controls. For each 1 μg/day-increase in cadmium intake, the OR for melanoma was 1.11 (95% CI 1.00–1.24). Melanoma risk generally increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99–2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12–2.75), and 1.65 (95% CI 1.05–2.61) for the second through fifth quintiles, compared with the lowest quintile. Sex-stratified analysis showed ORs per 1 μg/day-increase in cadmium intake of 1.10 (95% CI 0.93-1-29) among men and 1.15 (95% CI 0.99–1.33) among women. Using spline regression analysis, we observed a generally linear increase in melanoma risk up to 6 μg/day of cadmium intake, after which the risk appeared to plateau. ConclusionsWe observed a positive non-linear association between dietary cadmium intake and risk of cutaneous melanoma in a Northern Italy population. However, further studies are needed to elucidate this association, due to concerns about exposure misclassification, unmeasured confounding, and the limited and conflicting evidence from epidemiological findings.

Smoking and Cutaneous Melanoma: Findings from the QSkin Sun and Health Cohort Study.

Background: Previous studies suggest that smokers have lower risks of cutaneous melanoma than nonsmokers, but data from population-based prospective studies are scarce. We investigated associations between smoking and melanoma in a cohort study purpose-designed to investigate skin cancer outcomes.Methods: Participants with no prior history of melanoma (n = 38,697) completed a risk factor survey at baseline (2011). Patients were followed through linkage to the cancer registry. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between smoking (including intensity, duration, time since quitting) and melanoma using multivariate Cox proportional hazards regression, accounting for death as a competing event.Results: During a mean follow-up of 3.5 years, invasive melanomas developed in 247 participants. Compared with never smokers, former smokers (but not current smokers) had lower risks of invasive melanoma (HR 0.76; 95% CI, 0.57-1.01). Among former smokers, risks were lower with greater quantity of cigarettes smoked (HR 0.75; 95% CI, 0.56-0.98 per 10 cigarettes/day). No association was observed with duration of smoking while longer time since quitting was associated with a relative risk of melanoma that was not significantly different from the null (HR 1.18; 95% CI, 0.91-1.51, for every 10 years since quitting).Conclusions: We observed complex associations between smoking and melanoma, with some suggestion that former smokers had lower risks than never or current smokers. The apparent inverse association among former smokers may be due to residual confounding, although surveillance bias or biological effects cannot be excluded entirely.Impact: Smoking does not increase the risk of cutaneous melanoma. Cancer Epidemiol Biomarkers Prev; 27(8); 874-81. ©2018 AACR.

Risk of other Cancers in Families with Melanoma: Novel Familial Links

A family history of cutaneous melanoma (‘melanoma’) is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma.

Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necrosis factor therapy: analysis of the Australian Rheumatology Association Database (ARAD) prospective cohort study.

BackgroundMalignancy risk with tumour necrosis factor inhibitor (TNFi) therapy remains unclear. Our primary aim was to assess malignancy risk with TNFi therapy in a cohort of Australian patients with rheumatoid arthritis (RA). We also assessed risk in a biologic-naïve group.MethodsDemographic data of all RA patients enrolled in the Australian Rheumatology Association Database before 25 October 2010 were matched to national cancer records in July 2010 (linkage complete to 2007). Verified self-reported malignancies occurring between 1 January 2008 and 25 October 2010 were also included in the analysis. Standardised incidence ratios (SIRs) were used to compare malignancy incidence in biologic-naïve and TNFi-exposed ARAD participants to the general population using site-, age- and sex-specific rates by calendar year. Rate ratios (RRs) were used to compare malignancy incidence in TNFi-exposed participants to biologic-naïve RA patients, and a composite RA cohort that included pre-TNFi person years, both adjusted for age, gender, smoking, methotrexate use and prior malignancy.ResultsForty-four malignancies were reported after 5752 person-years in the TNFi-exposed group (N = 2145) and 32 malignancies were reported after 1682 person-years in the biologic-naïve group (N = 803). No overall increased risk of malignancy in TNFi-treated RA patients was found when compared with the general population or with biologic-naïve RA patients. Compared to the biologic naïve group, without the inclusion of pre-TNFi years in the comparator group, the relative risk of female breast cancer was reduced in TNFi-treated patients (RR 0.17 (95 % CI 0.03 to 0.95)). It was no longer significant when adding pre-TNFi years in the comparator group. The risk of melanoma was increased for both biologic naïve and TNFi-treated patients when compared with the general population (SIR 2.72 (95 % CI 1.13 to 6.53) and SIR 2.03 (95 % CI 1.09 to 3.78) respectively). The relative risk of melanoma was not increased in the TNFi-exposed group compared with biologic naïve patients (RR 0.54, 95 % CI 0.12, 2.40). Inclusion of pre-TNFi person years in the comparator group did not change these results.ConclusionsMalignancy incidence was low in this RA cohort and biologic exposure did not increase the risk of malignancy. Melanoma risk was increased in both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status, and possibly methotrexate exposure, may be responsible.

Serum Fatty Acids and Risk of Cutaneous Melanoma: A Population-Based Case-Control Study

Background. Some observational studies have suggested that excess dietary intake of polyunsaturated fatty acids such as linoleic acid increases cutaneous melanoma risk. We aimed at examining the association between serum fatty acids and melanoma risk by conducting a population-based case-control study in a northern Italy community. Methods. The percentage composition of 12 fatty acids was determined in 51 newly diagnosed melanoma patients and 51 age- and sex-matched population controls by extracting total lipids from serum samples using thin layer and gas chromatography. Conditional logistic regression was used to estimate the relative risk of melanoma associated with tertiles of percentage composition of each fatty acid as well as groupings including saturated, monounsaturated, and polyunsaturated fatty acids. Results. We found a slightly increased melanoma risk for stearic and arachidic acids proportion, with and without adjustment for potential confounders. For an n-3 polyunsaturated fatty acid, docosapentaenoic acid, we found a male-specific direct association with melanoma risk. No other associations emerged for the other saturated, monounsaturated, and polyunsaturated fatty acids, individually or grouped by type. Conclusions. These findings do not suggest a major role of fatty acids, including linoleic acid, on risk of cutaneous melanoma, though their evaluation is limited by the small sample size.

Melanoma and rheumatoid arthritis (brief report)

The aim of this study is to assess melanoma risk in rheumatoid arthritis (RA). A literature review was performed, retrieving observational studies over 1990-2010 that provided estimates of relative risk of melanoma associated with RA, compared to the general population. We generated standardized incidence ratio (SIR) estimates across all studies, first pooling the data and then performing a random-effects model to generate the SIRs. We retrieved 713 citations; after reviewing the titles and abstracts, 124 were further reviewed, and of these, 11 met our inclusion criteria for analysis. Pooling the data, there were a total of 601 melanomas that were observed over 1,351,061 patient-years of follow-up, or 4.4 cases per 10,000years. The expected number of melanomas over this interval was 596.2 for a pooled SIR of 1.01 [95% confidence interval (CI), 0.93, 1.09]. Excluding the two patient groups that were known to be exposed to biologics, the SIR estimate was unchanged (1.01; 95 CI, 0.93, 1.10). Our random-effects model similarly indicated an SIR for melanoma of 0.95 [95% credible interval (CrI), 0.86, 1.03] overall and 0.95 (95% CrI, 0.86, 1.04) excluding the two patient groups that were known to be exposed to biologics. These results do not highlight an important increased risk for melanoma in RA patients over-all, compared to the general population. It is not clear whether the risk is different for patients specifically exposed to biologic agents, although data are relatively few. Further study, especially of RA patients with a past history of melanoma, is warranted.

Risk of skin cancer in the drug treatment of rheumatoid arthritis

Background: It is well established that rheumatoid arthritis (RA) is associated with an increased risk of lymphoproliferative disorders when compared to the general population. It remains unclear whether this risk is owing to underlying inflammation and immune dysregulation, effects of disease modifying medications or a combination of the two. With increasing use of targeted biologic therapies, including those that may theoretically interfere with innate tumor surveillance, there is increasing concern about the development of other malignancies. Methods: The English language literature was searched to identify observational studies and clinical trials reporting incidence and relative risk of melanoma and non-melanoma skin cancer (NMSC) among RA patients. Results/conclusions: The numbers of melanomas reported were too small to draw conclusions regarding increased or decreased risk with underlying RA or commonly used medications. Relative incidence of NMSCs is difficult to assess given the lack of standardized reporting in the general population. No safety signal concerning skin cancer with RA or its therapies is at present identified.

The Prevalence of CDKN2A Germ-Line Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study

Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which "cases" have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and "controls" have incident first primary melanoma [single primary melanoma (SPM)]. Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma.

Risk of cutaneous malignant melanoma in patients with nonfamilial atypical nevi from a pigmented lesions clinic

Background: Atypical nevi (AN) are regarded as a major risk factor for occurrence of malignant melanoma. Few studies report an increase in relative risk for melanoma in patients with nonfamilial AN. Objective: We measured the risk of melanoma in 195 patients with nonfamilial AN. Methods: In a retrospective follow-up study the number of newly diagnosed melanomas during follow-up were inventoried. Included patients were invited for skin screening and nevus count. Results: On the basis of our calculations, the relative risk for invasive melanoma in patients with nonfamilial AN, including those patients with a history of melanoma, is 41. For individuals with AN without a previously diagnosed melanoma, the relative risk was 37. Multivariate analysis did not reveal a specific risk factor for the occurrence of melanoma (including number of AN) because of small numbers. Invasive melanomas occurred in persons having 1, 5, 12, and 172 AN, respectively. Conclusion: An increased risk for invasive cutaneous malignant melanoma in patients with nonfamilial AN was established.(J Am Acad Dermatol 1999;40:686-93.)

Hormonal and reproductive influences and risk of melanoma in women.

Evidence linking female hormones to the development of malignant melanoma has been contradictory. The purpose of this study was to examine the risk of melanoma in relation to exogenous and endogenous hormonal variables in women, including oral contraceptives, replacement oestrogens, pregnancy, and menopause. Hormonal and reproductive factors were evaluated using data from a personal-interview population-based case-control study of melanoma in women conducted in Connecticut during 1987-1989. Caucasian female incident invasive melanoma cases (n = 308) were confirmed by standardized histopathological review. Caucasian female controls (n = 233) were selected by random digit dialling and frequency-matched on age. Data were analysed using multivariate logistic regression. Ever being pregnant, age at first pregnancy, current use of replacement oestrogens, ever use of oral contraceptives, duration of use of oral contraceptives, and age at first use of oral contraceptives were not associated with melanoma. Among other variables, cases were more than twice as likely as controls to report a single pregnancy lasting >6 months, but this association lacked a dose-response relationship. Menopause and body mass index were not independently associated with risk of melanoma. However, this analysis did suggest that menopause and body mass index may be interactive risk factors. Melanoma cases were three times more likely than controls to be obese and report natural menopause when compared to thin/acceptable premenopausal women (OR = 3.00, 95% CI: 1.03-8.73). These data do not provide strong evidence that hormonal and reproductive factors are associated with risk of melanoma in women, although the few positive results should be explored further.

The risk of melanoma in patients with congenital nevi: A cohort study

Background: Giant congenital nevi are associated with a greatly increased risk of melanoma, but this has not been quantified. Smaller congenital nevi are believed by some authors to be associated with increased risk, but this is uncertain and needs to be clarified. Objective: Our purpose was to analyze cause-specific mortality and cancer incidence risks in patients with congenital nevi according to size of the nevi. Methods: We followed up 265 patients with congenital nevi first treated at the Hospital for Sick Children or at St. John's Hospital in London during 1950 to 1984 for mortality to mid-1993 and for cancer incidence from 1971 to 1989. Mortality and cancer incidence rates in the cohort were compared with expectations from national mortality and cancer incidence rates by sex, age, and calendar period. Results: Among the 33 patients with a congenital nevus covering at least 5% of the body area, two melanomas occurred during follow-up; both were fatal. The relative risk of melanoma mortality in these patients was 1046 (95% confidence interval, 127 to 3779). In the remaining 232 patients, 68 of whom had a nevus covering 1% to 4% of the body, and 164 with nevi smaller than 1% of body area, no melanomas occurred (0.18 melanoma deaths expected). The difference in melanoma mortality risk between the group with a nevus covering at least 5% of the body and the group with smaller nevi was significant ( p < 0.05). There was not a significantly increased risk of nonmelanoma mortality or of nonmelanoma cancer incidence overall in the cohort, although two lymphohematopoietic malignancies occurred. Conclusion: The data show the large risk of melanoma in patients with nevi covering more than 5% of the body surface area. The results do not support the hypothesis of greatly increased risk in persons with congenital nevi smaller than this, but because the confidence intervals of the result were wide, the data are compatible with a sizable risk. Much larger studies than those that have so far been undertaken, or combined analysis of data from several studies, are needed to quantify more precisely the risk of melanoma in relation to size of nevi and to determine the appropriate clinical management of these lesions.

Latitude gradients in melanoma incidence and mortality in the non-Maori population of New Zealand

The variation with latitude of incidence and mortality for cutaneous malignant melanoma (CMM) in the non-Maori population of New Zealand was assessed. For those aged 20 to 74 years, the effects of age, time period, birth-cohort, gender, and region (latitude), and some interactions between them were evaluated by log-linear regression methods. Increasing age-standardized incidence and mortality rates with increasing proximity to the equator were found for men and women. These latitude gradients were greater for males than females. The relative risk of melanoma in the most southern part of New Zealand (latitude 44 degrees S) compared with the most northern region (latitude 36 degrees S) was 0.63 (95 percent confidence interval [CI] = 0.60-0.67) for incidence and 0.76 (CI = 0.68-0.86) for mortality, both genders combined. The mean percentage change in CMM rates per degree of latitude for males was greater than those reported in other published studies. Differences between men and women in melanoma risk with latitude suggest that regional sun-behavior patterns or other risk factors may contribute to the latitude gradient observed.

Oral contraceptives and malignant melanoma

The effects if any which oral contraceptive (OC) use has on risk of illness has been widely studied. One such case-control study by Palmer et al. investigated the relationship between OC usage and the risk of developing cutaneous malignant melanoma. It is the Palmer report which serves as the basis of this commentary. The first area addressed the studys grouping criteria. Severe and nonsevere cases were grouped based on tumor thickness and presence of metastases. Palmer et al. concluded that OC use did not increase risk of cutaneous malignant melanoma. This report suggests that a selection bias was evident based on the differences in surveillance methods of OC users and nonusers. The authors then explain that if this bias was present one or both of two explanations must be true. The first explanation states that due to the studys increased level of surveillance many of the detected lesions would not have been diagnosed. The second explanation states that from the population a high proportion of OC users had initiated their own OC use recently and therefore the surveillance level would have been absent. Further they state that the relative risk of melanoma associated with OC use would be unchanged if either explanation was absent due to the lack of early detection efforts. A review of the literature on OC use and melanoma risk indicates that no clear relationship exists between them. The authors believe the Palmer et al. study to be a negative one if the assumption is made regarding the truly nonmalignant nature of some of the lesions being identified as melanoma.

Independence of dysplastic nevi from total nevi in determining risk for nonfamilial melanoma

In the determination of risk for melanoma, relatively little is known about the possible independence of two important predictors, total nevi and clinically dysplastic nevi. From a study conducted in Sydney, Australia [see J. J. Nordlund et al., Cancer Res. 45, 1855–1861 (1985)], 246 cases of melanoma (excluding 7% of targeted patients with a history of melanoma in a first-degree relative) were compared with 134 nonmelanoma controls. Participants had been examined by a dermatologist and an oncologist. Logistic regression analysis was used and included an age-sex interaction term in computing all estimates of relative risk in this report. Relative risk for melanoma in those with 16+ total nevi was significantly elevated at 1.8 but declined to a statistically nonsignificant level of 1.2 (95% confidence limit (CL): 0.7, 2.0) after adjustment for dysplastic nevi. In contrast, relative risk for melanoma in those with any dysplastic nevi was 7.6 (95% CL: 3.6, 16.0) but was maintained at a similarly elevated and statistically significant level of 7.7 (95% CL: 3.5, 17.1) after adjustment for total nevi. These patterns were even more evident in the younger half of the study population. The analyses suggest that much of the association between TN and nonfamilial melanoma is explained by the presence of dysplastic nevi and, conversely, they imply that dysplastic nevi represent a clinically distinct, qualitative disorder rather than simply a quantitative disorder wherein dysplastic nevi stem merely from an increase in total nevi. The dysplastic nevus syndrome accounts for 32% of all nonfamilial melanomas.

Melanocytic naevi and melanoma: an epidemiological perspective.

There is growing evidence that individuals at high risk of cutaneous melanoma can be identified by the use of simple measures of benign melanocytic naevi--raised risk occurring in persons who have large numbers of naevi, or naevi with atypical clinical features. Very high risk of melanoma appears to exist in two rare groups: persons with dysplastic naevi whose families include at least two individuals who have had melanoma, and persons with giant congenital naevi. Risks of melanoma in other individuals with dysplastic naevi and in persons with small congenital naevi have not yet been quantified. Much of the published work on risk of melanoma in relation to naevi has been based on clinical series or assemblage of case reports, with great potential for bias. In such studies, naevi have often been classified into dichotomies or syndromes originally defined for pathological or clinical purposes, frequently using poorly reproducible criteria. Case-control and cohort studies of the relationship of naevi to melanoma are needed, which use reproducible criteria and designs minimizing bias, and which examine risk in relation to graded clinical and histological measures of naevi.

Hormonal factors and melanoma in women.

The effect of exogenous hormones and reproductive factors on the risk of melanoma in women was investigated in a case-control study. Data from 91 women, aged from 15 to 81 years, and 91 matched controls were analysed in relation to use of oral contraceptives (OC), parity, age at the birth of the first child, and calculated length of ovulatory life. When potential confounding factors (including pigmentary characteristics and the lifetime exposure to sunlight were taken into account, there was no increase in risk of melanoma in relation to OC use, parity, or age at the birth of the first child. An unexplained association between melanoma and ovulatory life of greater length than 20 years was observed. The general findings of this study suggest that neither hormonal nor reproductive factors increase the risk of melanoma in women.

Pigmentary Traits, Ethnic Origin, Benign Nevi, and Family History as Risk Factors for Cutaneous Malignant Melanoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

The roles of constitutional factors and benign nevi in causation of malignant melanoma were examined in a case-control study of 511 patients and 511 matched controls in Western Australia. The strongest risk factor was the number of palpable benign nevi on a subject's arms. Compared to the risk of melanomas for persons having no palpable nevi on the arms, the relative risk of melanoma was 2.0 for persons with 1-4 nevi, 4.0 for persons with 5-9 nevi, and 11.3 for persons with 10 or more nevi (P less than .0001). Of the several pigmentary traits known to have associations with melanoma, inability to tan was the most important. Susceptibility to sunburn and hair color also had significant effects that were independent of tanning ability; however, after these traits were controlled, measured skin color and eye color had no additional effects. A reduced risk of melanoma was observed in persons having two or more Southern European grandparents [odds ratio (OR) = 0.39; P = .025]. Persons of Celtic origin did not have a significantly increased risk (OR = 1.18). Possession of one or more affected blood relatives was related to an increased risk of melanoma (OR = 2.69; P less than .0001). The effects of pigmentary traits, benign nevi, ethnic origin, and family history as risk factors were largely independent of one another.