Abstract
Melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin cancers. The incidence rates of all three types of skin cancers have increased in the past three decades. Light pigmentary traits have been recognized as one of the host risk factors for skin cancer, but findings on associations between eye colors and risk of skin cancers have been inconsistent.
We performed a prospective analysis to examine the association between eye colors and risk of skin cancers using the Health Professionals Follow-up Study (HPFS). Cox proportional hazard models were applied to estimate relative risks (RRs) and their 95% confidence intervals (CIs). Effect modifications due to hair color and skin reaction to sun were also examined.
The HPFS included 35,662 males. During a median follow-up of 19 years (1988–2012), 445 melanoma, 1123 SCC, and 7198 BCC cases were documented. Compared to those whose eye colors were dark or brown, participants with hazel/green/medium and blue/light colors had a 24% (RR = 1.24, 95% CI: 1.06–1.45) and a 19% (RR = 1.19, 95% CI: 1.01–1.41) higher risk of SCC, respectively. Similarly, a higher risk of BCC was observed in participants with hazel/green/medium eye colors (RR = 1.16, 95% CI: 1.09–1.23) and blue/light eye colors (RR = 1.17, 95% CI: 1.10–1.25). We did not find significant associations between eye color and risk of melanoma. Lighter eye color was associated with increased risks of SCC and BCC among those with dark hair colors (p for interaction ≤ 0.02).
In conclusion, in this large prospective study of men, we found that light eye colors were associated with higher risks of SCC and BCC, but not melanoma. Further studies are needed to confirm this association in other populations.
Similar content being viewed by others
Data availability
(data transparency): Information including the procedures to obtain and access data from the Health Professionals Follow-up Study is described at https://sites.sph.harvard.edu/hpfs/for-collaborators/.
Code availability
(software application or custom code): SAS software was used for all the data analyses in this study. The SAS code used in the current study is not publicly available due to the aforementioned data restrictions but will be available from the corresponding author upon request.
References
Apalla Z, Lallas A, Sotiriou E, Lazaridou E, Ioannides D (2017) Epidemiological trends in skin cancer. Dermatol Pract Concept 7:1–6
Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. CA Cancer J Clin 70:7–30
Housman TS, Feldman SR, Williford PM et al (2003) Skin cancer is among the most costly of all cancers to treat for the medicare population. J Am Acad Dermatol 48:425–429
Leiter U, Eigentler T, Claus G (2014) Epidemiology of skin cancer. Adv Exp Med Biol 810:120–140
Gandini S, Sera F, Cattaruzza MS et al (2005) Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur J Cancer 41:2040–2059
Walls AC, Han J, Li T, Qureshi AA (2013) Host risk factors, ultraviolet index of residence, and incident malignant melanoma in situ among US women and men. Am J Epidemiol 177:997–1005
Qureshi AA, Zhang M, Han J (2011) Heterogeneity in host risk factors for incident melanoma and non-melanoma skin cancer in a cohort of US women. J Epidemiol 21:197–203
Rosso S, Joris F, Zanetti R (1999) Risk of basal and squamous cell carcinomas of the skin in Sion, Switzerland: a case-control study. Tumori 85:435–442
Laino AM, Berry EG, Jagirdar K et al (2018) Iris pigmented lesions as a marker of cutaneous melanoma risk: an Australian case-control study. Br J Dermatol 178:1119–1127
Bliss J, Ford D, Swerdlow A et al (1995) Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: systematic overview of 10 case-control studies. The international melanoma analysis group (IMAGE). Int J Cancer 62:367–376
van Dam R, Huang Z, Rimm E et al (1999) Risk factors for basal cell carcinoma of the skin in men: results from the health professionals follow-up study. Am J Epidemiol 150:459–468
Khalesi M, Whiteman DC, Tran B, Kimlin MG, Olsen CM, Neale RE (2013) A meta-analysis of pigmentary characteristics, sun sensitivity, freckling and melanocytic nevi and risk of basal cell carcinoma of the skin. Cancer Epidemiol 37:534–543
Ferrucci LM, Cartmel B, Molinaro AM et al (2012) Host phenotype characteristics and MC1R in relation to early-onset basal cell carcinoma. J Invest Dermatol 132:1272–1279
Grigore M, Furtunescu F, Minca D, Costache M, Garbe C, Simionescu O (2018) The iris signal: blue periphery, tan collaret and freckles pattern - strong indicators for epidermal skin cancer in South-Eastern Europe. J Eur Acad Dermatol Venereol 32:1662–1667
Veierod MB, Weiderpass E, Thorn M et al (2003) A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst 95:1530–1538
Cust AE, Drummond M, Bishop DT et al (2019) Associations of pigmentary and naevus phenotype with melanoma risk in two populations with comparable ancestry but contrasting levels of ambient sun exposure. J Eur Acad Dermatol Venereol 33:1874–1885
Eiberg H, Mohr J (1996) Assignment of genes coding for brown eye colour (BEY2) and brown hair colour (HCL3) on chromosome 15q. Eur J Hum Genet 4:237–241
Pavan WJ, Sturm RA (2019) The genetics of human skin and hair pigmentation. Annu Rev Genomics Hum Genet 20:41–72
Sturm RA, Larsson M (2009) Genetics of human iris colour and patterns. Pigment Cell Melanoma Res 22:544–562
Han J, Kraft P, Nan H et al (2008) A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genet 4:e1000074
Lock-Andersen J, Drzewiecki K, Wulf H (1999) Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study. Acta Derm Venereol 79:74–80
Parra EJ (2007) Human pigmentation variation: evolution, genetic basis, and implications for public health. Am J Phys Anthropol Suppl 45:85–105
Duffy DL, Lee KJ, Jagirdar K et al (2019) High naevus count and MC1R red hair alleles contribute synergistically to increased melanoma risk. Br J Dermatol 181:1009–1016
Rebbeck T, Kanetsky P, Walker A et al (2002) gene as an inherited biomarker of human eye color. Cancer Epidemiol Biomark Prev 11:782–784
Fung TT, Spiegelman D, Egan KM, Giovannucci E, Hunter DJ, Willett WC (2003) Vitamin and carotenoid intake and risk of squamous cell carcinoma of the skin. Int J Cancer 103:110–115
van Dam R, Huang Z, Giovannucci E et al (2000) Diet and basal cell carcinoma of the skin in a prospective cohort of men. Am J Clin Nutr 71:135–141
VoPham T, Hart JE, Bertrand KA, Sun Z, Tamimi RM, Laden F (2016) Spatiotemporal exposure modeling of ambient erythemal ultraviolet radiation. Environ Health 15:111
Li WQ, Cho E, Weinstock MA, Li S, Stampfer MJ, Qureshi AA (2019) Cutaneous nevi and risk of melanoma death in women and men: a prospective study. J Am Acad Dermatol 80:1284–1291
Shaikh WR, Dusza SW, Weinstock MA, Oliveria SA, Geller AC, Halpern AC (2016) Melanoma thickness and survival trends in the United States, 1989 to 2009. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djv294
Graf J, Hodgson R, van Daal A (2005) Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation. Hum Mutat 25:278–284
Sturm RA, Duffy DL, Zhao ZZ et al (2008) A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet 82:424–431
Akey JM, Wang H, Xiong M et al (2001) Interaction between the melanocortin-1 receptor and P genes contributes to inter-individual variation in skin pigmentation phenotypes in a Tibetan population. Hum Genet 108:516–520
Johanson HC, Chen W, Wicking C, Sturm RA (2010) Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community. J Hum Genet 55:103–111
Duffy DL, Montgomery GW, Chen W et al (2007) A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet 80:241–252
Acknowledgments
We would like to thank the participants and staff of the Health Professionals Follow-up Study for their valuable contributions, as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.
Funding
The work was supported by the Health Professionals Follow-up Study (U01 CA167552). No funding supported study design and conduct; in the collection, management, analysis, and interpretation of data; in the preparation, review, or approval of the report; or in the decision to submit the article for publication.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare no potential conflicts of interest.
Ethical approval
The present study used secondary data from the Health Professionals Follow-up Study in which no participant identifying information was included.
Consent for publication
All authors of the current study consent for publication.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Li, Y., Li, WQ., Li, T. et al. Eye color and the risk of skin cancer. Cancer Causes Control 33, 109–116 (2022). https://doi.org/10.1007/s10552-021-01508-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-021-01508-z