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Melanoma

• Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC).
  Agricultural workers may be exposed to potential carcinogens including pesticides, sensitizing agents and solar radiation. Previous studies indicate increased risks of hematopoietic cancers and decreased risks at other sites, possibly due to differences in lifestyle or risk behaviours. Study present findings from CanCHEC (Canadian Census Health and Environment Cohort), the largest national population-based cohort of agricultural workers. Statistics Canada created the cohort using deterministic and probabilistic linkage of the 1991 Canadian Long Form Census to National Cancer Registry records for 1992-2010. A total of 9515 incident cancer cases (7295 in males) occurred in agricultural workers. Among men, increased risks were observed for non-Hodgkin lymphoma (HR = 1.10, 95% CI = 1.00-1.21), prostate (HR = 1.11, 95% CI = 1.06-1.16), melanoma (HR = 1.15, 95% CI = 1.02-1.31), and lip cancer (HR = 2.14, 95% CI = 1.70-2.70). Decreased risks in males were observed for lung, larynx, and liver cancers. Among female agricultural workers there was an increased risk of pancreatic cancer (HR = 1.36, 95% CI = 1.07-1.72). Increased risks of melanoma (HR = 1.79, 95% CI = 1.17-2.73), leukemia (HR = 2.01, 95% CI = 1.24-3.25) and multiple myeloma (HR = 2.25, 95% CI = 1.16-4.37) were observed in a subset of female crop farmers. Exposure to pesticides may have contributed to increased risks of hematopoietic cancers, while increased risks of lip cancer and melanoma may be attributed to sun exposure. The array of decreased risks suggests reduced smoking and alcohol consumption in this occupational group compared to the general population.
  [Kachuri L, Harris MA, MacLeod JS, et al. 2017. BMC Cancer. 17(1):343]
• A Review of the Association Between Parkinson Disease and Malignant Melanoma
  An association between melanoma and Parkinson disease (PD) has been hinted at in the neurology and oncology literature since the 1970s after the initiation of levodopa (L-DOPA) therapy for PD. Given that L-DOPA is a substrate in melanin synthesis, there existed a concern that this therapy might cause melanoma.The objective was to research possible etiological links to explain the connection between PD and melanoma. Patients with PD have an overall decreased risk of cancer diagnoses. However, breast cancer and melanoma have an uncharacteristically high rate of co-occurrence with PD. Family history of melanoma and lighter hair and skin color confer a higher risk of developing PD, and having a first-degree relative with either disease conveys a significantly increased risk of developing the other. Other possible connections that have been explored include pigmentation genes in neural-derived cells, pesticides, MC1R polymorphisms, and abnormal cellular autophagy. Although a link between PD and melanoma exists, the etiology of this link continues to be elusive. Both PD and melanoma are likely multifactorial diseases involving genetic and environmental risk factors.
  [Disse M, Reich H, Lee PK, Schram SS. 2016. Dermatol Surg. 42(2):141-6.]
• Occupational Exposure to Pesticides With Occupational Sun Exposure Increases the Risk for Cutaneous Melanoma.
  The objective of the study was to examine the association between occupational exposure to pesticides and cutaneous melanoma, controlling for all possible confounders.A pooled analysis of two case-control studies was conducted in two different geographic areas (Italy and Brazil). Detailed pesticides exposure histories were obtained. Ever use of any pesticide was associated with a high risk of cutaneous melanoma (odds ratio 2.58; 95% confidence interval 1.18-5.65) in particular exposure to herbicides (glyphosate) and fungicides (mancozeb, maneb), after controlling for confounding factors. When subjects were exposed to both pesticides and occupational sun exposure, the risk increased even more (odds ratio 4.68; 95% confidence interval 1.29-17.0). The study suggests an augmented risk of cutaneous melanoma among subjects with exposure to pesticides, in particular among those exposed to occupational sun exposure.
  [Fortes C, Mastroeni S, Segatto M M, Hohmann C, et al. 2016. J Occup Environ Med. 58(4):370-5. ]
• Residential and occupational exposure to pesticides may increase risk for cutaneous melanoma: a case-control study conducted in the south of Brazil.
  Incidences of primary cutaneous melanoma (CM) have risen over the last few decades, mainly among populations of White European extraction. Some risk factors for melanoma have been clearly established, but other potential risk factors, such as exposure to pesticides, are currently under study.A case-control study on melanoma was conducted during 2012 and 2013 at three dermatological reference centers in Porto Alegre, Brazil. A total of 191 CM patients and sex- and age-matched control subjects were enrolled in the study. Subjects exposed to pesticides had twice the level of risk for melanoma (odds ratio [OR] 2.03). When pesticides were used indoors for >10 years, the risk for CM increased further (OR 2.84). A high frequency of indoor use of pesticides (four or more times per year) was associated with a 44% increase in the risk for melanoma (OR 1.44). The domestic use of pesticides outdoors was not associated with increased risk. Subjects exposed to pesticides at an occupational level were at four times greater risk than subjects who were not occupationally exposed (OR 4.23).These findings indicate that the general use of pesticides, particularly indoor domestic use, frequently and over a long period, may be an independent environmental risk factor for CM.
  [Segatto MM, Bonamigo RR, Hohmann CB, Müller KR, et al. 2015. Int J Dermatol. doi: 10.1111/ijd.12826]
• Specific pesticide-dependent increases in α-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines.
  Epidemiological studies indicate a role of genetic and environmental factors in Parkinson's disease involving alterations of the neuronal α-synuclein (α-syn) protein. Objective was to precisely assess changes in α-syn levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines following acute exposure to pesticides (rotenone, paraquat, maneb, and glyphosate). These human cell lines express α-syn endogenously, and overexpression of α-syn (wild type or mutated A53T) can be obtained following recombinant adenoviral transduction. Study found that endogenous α-syn levels in the SH-SY5Y neuroblastoma cell line were markedly increased by paraquat, and to a lesser extent by rotenone and maneb, but not by glyphosate. Rotenone also clearly increased endogenous α-syn levels in the SK-MEL-2 melanoma cell line. In the SH-SY5Y cell line, similar differences were observed in the α-syn adenovirus-transduced cells, with a higher increase of the A53T mutated protein. Paraquat markedly increased α-syn in the SK-MEL-2 adenovirus-transduced cell line, similarly for the wild-type or A53T proteins. Data support the hypothesis that pesticides can trigger some molecular events involve malignant melanoma that consistently shows a significant but still unexplained association with Parkinson's disease.
  [Chorfa A, Bétemps D, Morignat E, Lazizzera C, et al. 2013. Toxicol Sci. 133(2):289-97.]
• Plasma levels of polychlorinated biphenyls and risk of cutaneous malignant melanoma: a preliminary study.
  This preliminary study examined the relationship between organochlorine compounds(OCC) residues in plasma and risk of cutaneous malignant melanoma (CMM) adjusting for sun sensitivity and sun exposure. A case-control study of 80 CMM patients and 310 control subjects was conducted. Lifetime sun exposure information, along with data on pigmentation variables and sun sensitivity data was collected, along with a blood sample. Strong associations were seen between risk of CMM and plasma levels of non-dioxin-like PCBs (Adjusted OR = 7.02) and several PCB congeners, organochlorine pesticides or metabolites. These associations persisted after control for sun sensitivity and sun exposure. Results from this investigation require independent confirmation in larger studies. However, they suggest that environmental factors other than UV radiation may play a role in genesis of CMM, and indicate that it may be productive to search for further agents which might increase risk.
  [Gallagher RP, Macarthur AC, Lee TK, Weber JP, et al. 2011. Int J Cancer. 128(8):1872-80]
• Pesticide Use and Cutaneous Melanoma in Pesticide Applicators in the Agricultural Heath Study
  Research finds found significant associations between cutaneous melanoma and maneb/mancozeb (>or= 63 exposure days: OR = 2.4), parathion (>or= 56 exposure days: OR = 2.4), and carbaryl (>or= 56 exposure days: OR = 1.7). Other associations with benomyl and ever use of arsenical pesticides are also suggested.
  [Dennis LK, et al. 2010. Environ Health Perspect. 118(6):812-7. Epub 2010 Feb 17.]
• Risk of childhood cancers associated with residence in agriculturally intense areas in the United States
  An ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for malignant bone tumors (OR 2.3) and for subtype osteosarcoma (OR 2.7) at high agricultural activity (greater than 60% of county acreage devoted to farming). Also linked to Ewing’s sarcoma (OR 4.3) and HL (OR 2.1) at high agricultural activity (greater than 60% of county acreage devoted to farming), and for oat crop acreage and Ewing’s (OR 2.3).
  [Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]
• Carbaryl exposure and incident cancer in the Agricultural Health Study
  Carbaryl is a carbamate insecticide with a broad spectrum of uses in agricultural, commercial and household settings. It has previously been linked with non-Hodgkin lymphoma (NHL) but studies of cancer risk in humans are limited. We examined occupational carbaryl use and risk of all cancers in the Agricultural Health Study, a prospective study of a cohort of pesticide applicators in North Carolina and Iowa. This analysis included 21,416 subjects (1,291 cases) enrolled from 1993-1997 and followed for cancer incidence through 2003. Pesticide exposure and other data were collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs) while controlling for potential confounders. Carbaryl was not associated with cancer risk overall. Relative to subjects who never used carbaryl, melanoma risk was elevated with >175 lifetime exposure-days (RR = 4.11; 95%CI, 1.33-12.75; p-trend = 0.07), >10 years of use (RR = 3.19; 95%CI, 1.28-7.92; p-trend = 0.04), or >or=10 days of use per year (RR = 5.50; 95%CI, 2.19-13.84; p-trend < 0.001). Risk remained after adjusting for sunlight exposure. Although not significant, there appeared to be a trend of decreasing prostate cancer risk with increasing level of exposure. A small increase in NHL risk was observed using some, but not all, exposure measures. No associations were observed with other examined cancer sites. Because the observed results were not hypothesized a priori and because of limited study of their biological plausibility, they should be interpreted with caution.
  [Mahajan, R., et al. 2007. Int J Cancer 121(8):1799-1805.]
• The association between residential pesticide use and cutaneous melanoma
  A case-control study of cutaneous melanoma finds an increased risk for indoor pesticide use four times a year (OR 2.18) compared to one time a year and for those exposed for 10 years or more an almost two and half times the risk as those exposed for less than 10 years indicating residential pesticide exposure may be a factor for cutaneous melanoma.
  [Fortes, C., et al. 2007. Eur J Cancer 43(6):1066-1075.]
• Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure
  A study in Costa Rica finds heavy pesticide use in rural counties is associated with an increase risk for skin melanoma cancer in males (OR 1.77).
  [Wesseling, C., et al. 1999. International Journal of Epidemiology 28:365-374.]