Skip to main content


Log in

Eye color and the risk of skin cancer

  • Original Paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript


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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

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

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.


  1. Apalla Z, Lallas A, Sotiriou E, Lazaridou E, Ioannides D (2017) Epidemiological trends in skin cancer. Dermatol Pract Concept 7:1–6

    Article  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. CA Cancer J Clin 70:7–30

    Article  Google Scholar 

  3. 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

    Article  Google Scholar 

  4. Leiter U, Eigentler T, Claus G (2014) Epidemiology of skin cancer. Adv Exp Med Biol 810:120–140

    PubMed  Google Scholar 

  5. 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

    Article  Google Scholar 

  6. 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

    Article  Google Scholar 

  7. 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

    Article  Google Scholar 

  8. 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

    Article  CAS  Google Scholar 

  9. 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

    Article  CAS  Google Scholar 

  10. 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

    Article  CAS  Google Scholar 

  11. 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

    Article  Google Scholar 

  12. 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

    Article  Google Scholar 

  13. 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

    Article  CAS  Google Scholar 

  14. 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

    Article  CAS  Google Scholar 

  15. 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

    Article  Google Scholar 

  16. 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

    Article  CAS  Google Scholar 

  17. 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

    Article  CAS  Google Scholar 

  18. Pavan WJ, Sturm RA (2019) The genetics of human skin and hair pigmentation. Annu Rev Genomics Hum Genet 20:41–72

    Article  CAS  Google Scholar 

  19. Sturm RA, Larsson M (2009) Genetics of human iris colour and patterns. Pigment Cell Melanoma Res 22:544–562

    Article  CAS  Google Scholar 

  20. 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

    Article  Google Scholar 

  21. 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

    Article  CAS  Google Scholar 

  22. Parra EJ (2007) Human pigmentation variation: evolution, genetic basis, and implications for public health. Am J Phys Anthropol Suppl 45:85–105

    Article  Google Scholar 

  23. 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

    Article  CAS  Google Scholar 

  24. 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

    CAS  Google Scholar 

  25. 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

    Article  CAS  Google Scholar 

  26. 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

    Article  Google Scholar 

  27. 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

    Article  Google Scholar 

  28. 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

    Article  Google Scholar 

  29. 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.

    Article  PubMed  Google Scholar 

  30. 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

    Article  CAS  Google Scholar 

  31. 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

    Article  CAS  Google Scholar 

  32. 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

    Article  CAS  Google Scholar 

  33. 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

    Article  Google Scholar 

  34. 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

    Article  CAS  Google Scholar 

Download references


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.


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

Correspondence to Eunyoung Cho.

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: