Tattoos and cutaneous squamous cell carcinoma: a population-based case-control study

The popularity of tattoos has increased dramatically over the last few decades. Tattoo ink often contains carcinogenic chemicals, e.g., primary aromatic amines, polycyclic aromatic hydrocarbons, and metals. The tattooing process invokes an immunologic response that causes translocation of tattoo ink from the injection site. Deposition of tattoo pigment in lymph nodes has been confirmed but the long-term health effects remain unexplored. We used Swedish National Authority Registers with full population coverage to investigate the association between tattoo exposure and overall malignant lymphoma as well as lymphoma subtypes. We performed a case-control study where we identified all incident cases of malignant lymphoma diagnosed between 2007 and 2017 in individuals aged 20-60 years in the Swedish National Cancer Register. Three random age- and sex-matched controls per case were sampled from the Total Population Register using incidence density sampling. We assessed exposure through a questionnaire in 2021, and data on potential confounders were retrieved from registers. We used multivariable logistic regression to estimate the incidence rate ratio (IRR) of malignant lymphoma in tattooed individuals. The study population consisted of 11,905 individuals, and the response rate was 54% among cases (n=1398) and 47% among controls (n=4193). The tattoo prevalence was 21% among cases and 18% among controls. Tattooed individuals had a higher adjusted risk of overall lymphoma (IRR=1.21; 95% CI 0.99-1.48). The risk of lymphoma was highest in individuals with less than two years between their first tattoo and the index year (IRR=1.81; 95% CI 1.03-3.20). The risk decreased with intermediate exposure duration (three to ten years) but increased again in individuals who received their first tattoo ≥11 years before the index year (IRR=1.19; 95% CI 0.94-1.50). We found no evidence of increasing risk with a larger area of total tattooed body surface. The risk associated with tattoo exposure seemed to be highest for diffuse large B-cell lymphoma (IRR 1.30; 95% CI 0.99-1.71) and follicular lymphoma (IRR 1.29; 95% CI 0.92-1.82). Our findings suggested that tattoo exposure was associated with an increased risk of malignant lymphoma. More epidemiologic research is urgently needed to establish causality. The Swedish Research Council for Health, Working Life and Welfare.

Intake of Alcohol May Modify the Risk for Non-Melanoma Skin Cancer: Results of a Large Danish Prospective Cohort Study

Recipients of solid organ transplants are at a markedly increased risk of cutaneous squamous cell carcinoma (SCC). We investigated potential associations between post-transplant infections, HLA type, and other transplant-related factors and risk of SCC, taking immuno-suppressive treatment into account. A population-based case-control study was conducted. All patients who developed SCC during follow-up (1970-1997) were eligible as cases (n = 207). Controls (n = 189) were individually matched to the cases on age and calendar period of transplantation. Detailed exposure information was collected through an extensive, blinded review of medical records. Odds ratios were computed with conditional logistic regression. There were no significant associations with any infectious agents, or with number and timing of infections, specific HLA-type, donor characteristics, or other transplant characteristics and risk of post-transplant SCC. These results suggest that risk of post-transplant SCC is neither closely related to specific post-transplant infectious disorders, nor to the infectious load or specific HLA types.

The purpose of this study was to investigate associations between occupation, nonsolar environmental exposures, and risk of squamous cell carcinoma (SCC) of the skin. Data from the Southeastern Arizona Health Study-2 were used. This was a population-based case-controlled study [n = 795) conducted during 1992-1996 in southeastern Arizona to primarily assess the risk of skin SCC in relation to sun exposure. Multivariate logistic regression was used to calculate odd ratios as the estimate of effect. High-risk occupations were identified through literature review. There was evidence of a slightly elevated risk of skin SCC for subjects reporting a history of construction work (OR = 1.38, 95 % CI = 0.61-3.14), and automobile and machine work (OR = 1.21, 95 % CI = 0.48-3.06) Furthermore, there were no statistically significant associations between risk of skin SCC and history of exposure to specific chemical and other nonsolar environmental agents. A slight indication of increased risk for skin SCC was noted for exposure to nonsolar light (OR = 1.33, 95 % CI = 0.92-2.26), construction/machinery materials (OR = 1.12, 95 % CI = 0.76-1.84), fluorescent light (OR = 1.56, 95 % CI = 0.92-2.61), gypsum (OR = 1.84, 95 % CI = 0.68-5.0), coal tar and dandruff shampoos (OR = 1.28, 95 % CI = 0.85-1.9), and cement dust (OR = 1.81, 95 % CI = 0.90-3.62). A large although statistically insignificant risk was seen for exposure to arsenic (OR = 4.21, 95 % CI = 0.40-43.9) and ethylene glycol (OR = 8.46, 95 % CI = 0.77-92.9). Several of the results of this analysis are consistent with literature and conclusions from previous epidemiological studies. However, lack of power and small sample size deem these results as inconclusive until more research and larger studies are conducted.

Oral tongue cancer incidence has increased among whites in the United States; however, the cause remains unknown. If an infectious agent is implicated, then elevated risk would be expected among immunosuppressed individuals. By using population-based registry linkage information from the US Transplant Cancer Match and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) Cancer Match studies, the authors examined the risk of oral tongue squamous cell carcinoma (SCC) among immunocompromised transplantation recipients and HIV-infected individuals. In addition, the risks of oropharyngeal SCC (strongly related to human papillomavirus infection; modestly affected by immunosuppression), other tobacco/alcohol-related oral cavity SCCs (not thought to be infection/immunosuppression-related), and non-Hodgkin lymphoma of oral cavity/pharynx (strongly related to Epstein-Barr virus; profoundly affected by immunosuppression) were evaluated. Compared with the general population, the risk of non-Hodgkin lymphoma was strongly increased (standardized incidence ratio [SIR] > 8.0). The risk of all SCCs was modestly and similarly elevated among transplantation recipients (SIR range, 2.2-2.7; Pheterogeneity = .2); whereas, among HIV-infected individuals, the risk of oral tongue SCC was higher compared with the risk of other SCCs (SIR, 3.0 vs 1.7 [for oropharyngeal SCCs] and 2.3 [for other oral cavity SCCs]; Pheterogeneity < .001). The risk of SCCs was significantly higher among men, older individuals, and whites; and risk increased with the time since transplantation/AIDS onset. The risk of oral tongue SCC was significantly higher among HIV-infected men who have sex with men compared with the average risk in HIV-infected individuals (adjusted incidence rate ratio = 2.0). Similar modest increases in the risk of oral tongue and other oral cavity SCCs do not suggest that an infectious agent or exposure profoundly affected by immunosuppression underlies the increase in oral tongue cancer. Cancer 2018;124:2515-22. © 2018 American Cancer Society.

Lung transplant recipients (LTR) are at high risk of cutaneous squamous cell carcinoma (SCC). Voriconazole exposure after lung transplant has recently been reported as a risk factor for SCC. We sought to study the relationship between fungal prophylaxis with voriconazole and the risk of SCC in sequential cohorts from a single center. We evaluated 400 adult LTR at UCLA between 7/1/2005 and 12/22/2012. On 7/1/2009, our center instituted a protocol switch from targeted to universal antifungal prophylaxis for at least 6 months post-transplant. Using Cox proportional hazards models, time to SCC was compared between targeted (N = 199) and universal (N = 201) prophylaxis cohorts. Cox models were also used to assess SCC risk as a function of time-dependent cumulative exposure to voriconazole and other antifungal agents. The risk of SCC was greater in the universal prophylaxis cohort (HR 2.02, P < 0.01). Voriconazole exposure was greater in the universal prophylaxis cohort, and the cumulative exposure to voriconazole was associated with SCC (HR 1.75, P < 0.01), even after adjustment for other important SCC risk factors. Voriconazole did not increase the risk of advanced tumors. Exposure to other antifungal agents was not associated with SCC. Voriconazole should be used cautiously in this population.

The risk of cancer is not increased in patients with multiple kidney transplantations

To investigate the pRb expression in a large group of patients with history of chronic exposure to the main risk factors for development of squamous cell carcinoma of the esophagus. One hundred and seventy asymptomatic individuals at high risk for esophageal squamous cell carcinoma (consumption of more than 80 g of ethanol and 10 cigarettes/d for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa. As a control group, specimens of esophageal mucosa obtained from 20 healthy subjects were also studied. Immunohistochemical assessment of the tissues was performed using a monoclonal antibody anti-pRB protein. Absence of the pRB staining, indicating loss of RB function, was observed in 33 (19.4%) of the individuals at risk for esophageal cancer, but in none of the healthy controls (P < 0.02). Loss of pRb expression increased in a stepwise fashion according to the severity of the histological findings (P < 0.005): normal mucosa (11/97 or 11.3%), chronic esophagitis (17/60 or 28.3%), low-grade dysplasia (3/10 or 30%), high-grade dysplasia 1/2 or 50%) and squamous cell carcinoma (1/1 or 100%). Our findings suggest that abnormal expression of the pRB protein may be implicated in the process of esophageal carcinogenesis. Additional studies are warranted to define the role of the pRB protein as a biomarker for development of esophageal squamous cell carcinoma in individuals at high risk for this malignancy.

Background: We previously reported that cutaneous human papillomavirus (HPV) infection was associated with significantly increased risk of cutaneous squamous cell carcinoma (SCC), while longer telomeres were associated with significantly reduced risk of SCC. We conducted further research to evaluate the interaction between cutaneous HPV and telomere length in association with SCC. Methods: Previously, a clinic based case-control (173 SCC cases and 300 controls) study was conducted, between 2007-2008, at the University of South Florida and Moffitt Cancer Center. HPV seropositivity (33 types) and DNA positivity (25 beta-HPV types) in eyebrow hairs (EB) and SCC tumors were measured using multiplex assays. Using quantitative PCR, relative telomere length was measured in peripheral blood leukocytes by determining the ratio of telomere repeat copy number to a single-copy gene copy number for each sample. For the present analyses, subjects with available data on telomere length and a) HPV serology (135 cases and 201 controls), b) HPV DNA in EB (130 SCC cases and 195 controls) and c) HPV DNA in SCC tumors (117 cases), were included. Association between telomere length and SCC was examined after stratification by HPV serostatus and HPV DNA status in EB, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age and gender. Results: Telomere length did not differ significantly between beta-HPV seronegative (mean = 1.16, standard deviation (SD) = 0.57) and seropositive controls [mean (SD) = 1.24(0.75), P value = 0.56], or by tumor HPV DNA status (P value = 0.93). Longer telomere length was associated with significantly reduced risk of SCC among subjects seronegative to all HPV types or seropositive to a single beta1 HPV type (OR = 0.01, 95% CI = 0.001-0.10), while no association was observed among those seropositive to &amp;gt;1 beta1 HPV types (OR = 1.01, 95% CI = 0.95-1.07, Pinteraction = &amp;lt;0.0001). A significant interaction (Pinteraction = 0.0004) was also observed between telomere length and DNA positivity for &amp;gt; = 1 beta-HPV types in EB in association with SCC (OREB DNA negative = 0.003, 95% CI = &amp;lt;0.001-0.09; OREB DNA positive = 1.02, 95% CI = 0.98-1.06). Further, longer telomere length was associated with 62% (OR = 0.38, 95% CI = 0.19-0.75, Pinteraction = 0.004) and 55% (OR = 0.45, 95% CI = 0.23-0.90, Pinteraction = 0.01) reduced risk of SCC among subjects DNA negative for all beta-HPV types or positive for a single beta1 or beta2 type, respectively, while no associations were observed among those with EB DNA positivity for &amp;gt;1 beta1 or beta2 types (OR = 1.02, 95% CI = 0.98-1.07 for both groups). In summary, multiple beta-HPV infections showed significant statistical interaction with telomere length in association with SCC. Conclusion: Presence of cutaneous HPV infection may attenuate the protective effect of longer telomeres on the risk of SCC. Citation Format: Shalaka S. Hampras, Michael Pawlita, Massimo Tommasino, Jong Park, Pearlie K. Burnette, Neil A. Fenske, Basil A. Cherpelis, Dana E. Rollison. Interaction between cutaneous human papillomavirus infection and telomere length in association with cutaneous squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3439.

Few epidemiologic studies are available that quantify the magnitude of the risk of squamous cell carcinoma (SCC) of the skin associated with sun exposure and related factors such as skin type. In addition, several studies have found an association between cigarette smoking and SCC. We prospectively examined the risk of developing SCC in relation to phenotype and the effects of sun exposure, as well as to cigarette smoking and other factors, during 8 years of follow-up in a cohort of 107,900 predominantly white women aged 30-55 years at base line in 1976. Questionnaires regarding medical history and health-related variables were sent to Nurses' Health Study participants every 2 years, beginning in 1976. Information on constitutional factors (natural hair color, childhood and adolescent tendency to sunburn and tan, and lifetime number of severe sunburns), lifestyle factors (regular time spent outdoors in the summer and sunscreen use), the state lived in at birth and at ages 15 and 30 years, and cigarette smoking habits were ascertained by questionnaire. A total of 197 women with first-incident, histologically confirmed, invasive SCCs that were diagnosed from 1982 to 1990 were included in this analysis. Multivariate analysis using proportional hazards models was used to calculate the relative risks (RRs) and corresponding 95% confidence intervals (CIs), with adjustment for confounders. The risk of SCC was increased in women living in California (RR = 1.8; 95% CI = 1.3-2.6) and Florida (RR = 2.1; 95% CI = 1.1-3.9) at base line, compared with those living in the northeastern states. This risk was higher for women living in those states at birth and at 15 years of age (RR = 2.5; 95% CI = 1.4-4.4 for California and RR = 3.0; 95% CI = 0.7-1.2 for Florida). Red (RR = 2.0; 95% CI = 1.1-3.7) and light brown (RR = 1.7; 95% CI = 1.2-2.4) hair colors were associated with an increased risk of SCC, compared with dark brown hair. After adjusting for the number of sunburns, women who tended to burn after 2 or more hours of sun exposure as children had a slightly higher risk of SCC than those who never burned (RR = 1.5; 95% CI = 0.9-2.5 for burn and RR = 1.1; 95% CI = 0.6-2.0 for painful burn), although the actual number of severe burns appeared to be a more important factor (RR = 2.4; 95% CI = 1.5-4.0 for six or more burns). Finally, current cigarette smokers showed a 50% increase in the risk of SCC compared with never smokers (RR = 1.5; 95% CI = 1.1-2.1). Exposure to the sun leading to sunburn, particularly at early ages, should be avoided to decrease the risk of incident SCC.

Current evidence about the association between voriconazole and risk of cutaneous squamous cell carcinoma (SCC) remains inconsistent. To assess the association between voriconazole use and risk of SCC. We systematically searched PubMed and Embase and performed a random effects model meta-analysis to calculate the pooled relative risk (RR) with a 95% confidence interval (CI). Of the 8 studiesinvolving a total of 3710 individuals with a lung transplant or hematopoietic cell transplant that were included in the qualitative analysis, 5 were included in the meta-analysis. Use of voriconazole was significantly associated with increased risk of SCC (RR, 1.86; 95% CI, 1.36-2.55). The increased risk did not differ according to type of transplantation or adjustment for sun exposure. Longer duration of voriconazole use was found to be positively associated with risk of SCC (RR, 1.72; 95% CI, 1.09-2.72). Voriconazole use was not associated with increased risk of basal cell carcinoma (RR, 0.84; 95% CI, 0.41-1.71). There were some heterogeneities in the retrospective observational studies. Our findings support an increased risk of SCC associated with voriconazole in individuals with a lung transplant or hematopoietic cell transplant. Routine dermatologic surveillance should be performed, especially among individuals at high risk of developing SCC.

The risk of cutaneous squamous cell carcinoma (CSCC) is found to be substantially increased after organ transplantation. The association with specific immunosuppressive regimens has been previously investigated, but results are not concordant. We aimed to clarify the relationship between separate immunosuppressive drugs, drug load, timing and risk of post-transplant CSCC. A population-based nested case-control study was performed in the Swedish organ transplantation cohort (n = 5931). All patients who developed CSCC during the follow-up (1970-97) were eligible as cases (n = 207). Controls (n = 189) were randomly selected from the cohort and individually matched to the cases on follow-up time, age at and calendar period of transplantation. Exposure information was collected through extensive and standardized review of medical records. The median time to CSCC was 6.7 years. Post-transplant azathioprine (Aza) treatment considerably increased the risk of CSCC during all time periods analysed, and the risk augmented with increasing dose and duration. Patients who after the entire follow-up period had received a high accumulated dose of Aza had an 8.8-fold increased risk of CSCC in multivariate analysis (P < 0.0001), compared to patients never treated with Aza. Additionally, a high accumulated dose of corticosteroids during the same period conferred a 3.9-fold elevated risk of CSCC (P = 0.09), compared to the lowest accumulated dose of corticosteroids. Cyclosporine treatment was not associated with the risk of CSCC post-transplantation. This study provides evidence that Aza treatment, but not cyclosporine treatment, is strongly associated with post-transplant CSCC risk. The results suggest that the risk of CSCC after organ transplantation is not only an effect of the immunosuppressive load per se.

Non-melanoma skin cancer is the most common cancer in humans and the most important risk factors are thought to be age, skin type, and exposure to ultraviolet radiation. Lifestyle factors may also play a part. To date no systematic review has been performed to collate evidence of the effects of smoking, alcohol or body mass index. We performed a systematic review and meta-analysis to assess the effects of smoking, alcohol and body mass index on the risk of non-melanoma skin cancer and its subtypes. Adults (18+ years old) of either sex from any ethnicitySmoking, alcohol, or body mass index (including other anthropometric measurements, such as weight, waist to hip ratio, and the percentage body fat)Non-melanoma skin cancer, cutaneous squamous cell carcinoma, or basal cell carcinomaComparative observational epidemiological studies SEARCH STRATEGY: We performed a comprehensive search of MEDLINE, EMBASE, CINAHL, Cochrane Library and CAB Abstracts from inception to October 2010. We also scanned reference lists to identify further eligible studies. Data from eligible studies were extracted and quality assessed using the Newcastle Ottawa Scale independently by two reviewers. The titles, abstracts and full text identified from the search were assessed independently by two reviewers against pre-specified inclusion/exclusion criteria. Disagreements were resolved through discussion with a third reviewer. For studies with similar exposures, a meta-analysis was performed using a random effects model and results were expressed as pooled odds ratio with 95% confidence intervals. Heterogeneity was assessed using I. Publication bias was assessed using funnel plots. Data were analysed using Review Manager. Thirty studies were included of which 22 used a case control design and the remaining used a cohort design. The overall quality of the studies was variable with a Newcastle Ottawa Scale median score of 6 out of 9 stars. No evidence of asymmetry was detected in the funnel plots. Smoking was not significantly related to increased risks of non-melanoma skin cancer (Odds Ratio 0.62, 95% CI 0.21 to 1.79, I=34%, 2 studies) or basal cell carcinoma (Odds Ratio 0.95, 95% CI 0.82 to 1.09; I=59%, 14 studies). However, smoking was significantly associated with a 52% increase in the risk of cutaneous squamous cell carcinoma (95% CI 1.15 to 2.01; I=64%; 6 studies). Subgroup analysis found no significant difference in results based on the definition of smoking (current, former, or ever smoker) for basal cell carcinoma, cutaneous squamous cell carcinoma or non-melanoma skin cancer. Alcohol was not significantly related to increased risks of non-melanoma skin cancer (1 study), basal cell carcinoma (Odds Ratio 1.03, 95% CI 0.94 to 1.13, I=0%, 9 studies) or cutaneous squamous cell carcinoma (1 study). Similar results were found irrespective of the type of alcohol assessed (beer, wine, or spirits) for basal cell carcinoma and cutaneous squamous cell carcinoma. A pooled analysis of five studies found a non-significant decrease in the risk of basal cell carcinoma associated with a higher body mass index (Odds Ratio 0.94, 95% CI 0.84 to 1.04, I=40%). In a subgroup analysis based on sex, the potential reduction in risk of basal cell carcinoma appeared to be confined to males (Males: Odds Ratio 0.90, 95% CI 0.78 to 1.04, I=45%, 4 studies; Females: Odds Ratio 1.01, 95% CI 0.85 to 1.19, I=14%, 3 studies). It is unclear at present if smoking modifies the risk of basal cell carcinoma; however, smoking clearly increases the risk of cutaneous squamous cell carcinoma. Limited evidence has been published about the risk of non-melanoma skin cancer with alcohol and body mass index; however there is some suggestion a high body mass index may be slightly protective of basal cell carcinoma, particularly in males.This study highlights the importance for clinicians to actively survey high risk patients, including current smokers.The majority of studies included in this systematic review assessed the associations between basal cell carcinoma and smoking, alcohol or body mass index. However, more evidence is needed before conclusive recommendations can be formed regarding the relationship between cutaneous squamous cell carcinoma and alcohol or body mass index.

Background: Carcinogens have been observed in many tattoo inks which can form new carcinogenic compounds when exposed to ultraviolet radiation and can accumulate in the lymph nodes and other organs. Tattooing can result in short- and long-term inflammatory and immune responses. At least 38 cases of melanoma have been reported in tattoos. The incidence of melanoma in Utah is the highest in the U.S., and potentially modifiable risk factors are of public health interest. In this study, we evaluated associations between tattooing and melanoma risk. Methods: We utilized a population-based case-control study of 514 incident in situ (284 men and 230 women) and 534 invasive (285 men and 249 women) melanoma cases diagnosed in Utah between 2020-2021. Controls (n=5,240) were selected from respondents to the Utah Behavioral Risk Factor Surveillance System (BRFSS) survey and frequency matched to cases in a 5:1 ratio on sex, age, race, and ethnicity. We fit logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) associating ever tattooing with in situ and invasive melanoma risk, adjusting for age, education level, race, and ethnicity, separately for women and men. We then fit logistic models stratified by education level (&amp;lt; four-year college degree/four-year college degree or more) and models stratified by age (&amp;lt; 50 years/50+ years), separately for women and men. Results: Among men, the prevalence of tattooing was 7% for both in situ and invasive cases, and 11% for controls. Among women, tattooing prevalence was 20% for in situ cases, 15% for invasive cases, and 18% for controls. Ever tattooing was associated with decreased invasive melanoma risk among men (OR=0.62 [95% CI: 0.37-1.02]), particularly among those who had less than a four-year college degree (0.52 [0.28-0.99]), and among ages 50+ (0.36 [0.16-0.84]). Among men, the OR for ever tattooing and in situ melanoma was in the same direction as invasive melanoma, but the estimate was statistically imprecise (0.73 [0.45-1.19]). Among women, we did not observe an association between ever tattooing and invasive melanoma (0.83 [0.56-1.20]), while the association between ever tattooing and in situ melanoma was statistically imprecise (1.25 [0.87-1.80]). However, ever tattooing was associated with a nearly two-fold increased risk of in situ melanoma among women with a four-year college degree (1.98 [1.21-3.26]), but not for those without a college degree (0.89 [0.52-1.50]). Conclusion: These findings do not suggest that there is an association between tattooing and melanoma. Associations between tattooing and health-seeking behaviors, which may vary by sex and other demographic factors, may influence associations with melanoma diagnosis, particularly for in situ melanoma. This study is the first step in investigating whether reported cases of melanoma arising in tattoos are coincidental or whether tattoos may be associated with an increased risk of melanoma. Citation Format: Rachel D. McCarty, Britton Trabert, Morgan M. Millar, David Kriebel, Laurie Grieshober, Mollie E. Barnard, Lindsay J. Collin, Katherine A. Lawson-Michod, Jeffrey A. Gilreath, Douglas Grossman, John Hyngstrom, Paul J. Shami, Jennifer A. Doherty. Tattooing and risk of melanoma: A population-based case-control study in Utah [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2209.

Differential effects of fatty acids on carcinogenesis suggest that fatty acid composition is important in tumor development. Arachidonic acid and its metabolites elicit inflammation and promote tumor formation in mouse skin. Inhibitors of the arachidonic cascade inhibit tumor incidence. A population-based case control study in Southeastern Arizona tested the hypothesis that lower levels of arachidonic acid in RBC membranes were associated with decreased risk of skin squamous cell carcinoma (SCC; n = 335 SCC cases and 321 controls). Extracted and esterified RBC fatty acids were analyzed using capillary gas chromatography. Individual peaks for 14 fatty acids were measured as a percentage of total fatty acids. Logistic regression was used to estimate odds ratios (OR), adjusting for SCC risk factors (age, gender, actinic keratosis history, freckling, and tanning ability). Increased levels of arachidonic acid in RBC membranes were associated with increased risk of SCC [odds ratio (OR), 1.08 per mg/100 mL change; 95% confidence interval (95% CI), 1.02-1.15] and this association remained when controls with actinic keratosis precursor lesions were excluded. SCC risk was highest among the upper quartile of arachidonic acid (OR, 2.38; 95% CI, 1.37-4.12). In contrast, increasing proportions of palmitic acid (OR, 0.94; 95% CI, 0.89-1.00) and palmitoleicacid (OR, 0.49; 95% CI, 0.30-0.81) were associated with reduced SCC risk. More studies are needed to elucidate the function of RBC fatty acids so that recommendations can be made to alter the human diet for cancer prevention.