Risk Factors for Melanoma by Anatomic Site

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• The authors analyzed data from 2617 first invasive melanomas (975 controls) from two population-based case–control studies in Australia and the UK. They found that the incidence of melanoma was highest on the trunk (35%) and lower limbs (34%) and was lower for the upper extremities (20%) and head and neck sites (11%). Men had a higher frequency of melanoma on the head and neck, whereas women more frequently had disease on the extremities. Melanomas occurred more often on the head and neck than on any other site in patients older than 70 years. Higher density of nevi was associated with higher odds for melanoma across all sites, but a stronger association was seen with many nevi and melanoma on the trunk and extremities. Very fair skin type was associated with melanoma on nontruncal locations.

• This study sheds light on the factors that affect the risk of developing melanoma and how they vary based on the anatomic site of the melanoma. These data support the dual-pathway hypothesis, which holds that truncal melanomas are more strongly related to nevi and intermittent sun exposure, while head and neck melanomas are more related to chronic sun exposure.

– Caroline K. Crabtree, MD

Written by

 

 

Darrell S. Rigel MD, MS

Written by

 

 

Justin W. Marson MD

This study builds on prior work by Day et al1,2 and Sober et al3 that found various risk factors (including the anatomical location of melanomas) affected mortality and outcomes, and it seeks to determine if there are different etiologies for melanomas arising on different anatomic locations. The "dual pathway hypothesis" suggests that melanoma of the trunk (and less sun–exposed areas) is driven by materially different, more intrinsic factors than melanoma of the head and neck (more sun–exposed areas). To do so, the authors of this study investigated the variation between different risk factors (hair/eye color, number of nevi, skin tone, UV exposure, polygenic risk scores) and melanomas found on different anatomical sites (trunk, head and neck, upper limbs, and lower limbs).

The study collected data and DNA samples from 2617 patients, primarily of European descent, with a first-time diagnosis of invasive melanoma and 975 age-, sex-, and geographically matched controls using data obtained from an Australian and UK case–control cohort. Overall, the authors found that an increasing number of nevi corresponded with truncal melanoma and that, after controlling for additional phenotypic differences, weekday UV exposure (a proxy for weekday sun exposure) was only associated with head and neck melanomas. The authors propose that these data support the notion of dual pathways for melanomas of the trunk versus head and neck with potential convergence of these pathways for melanomas of the limbs.

Interestingly, UV exposure was not independently associated with increased risk of melanoma at other anatomic sites. The authors suggest that this may be due to a potential modifying association with skin phenotype. There was also not a significant variation in the association between polygenic risk factors and melanoma across anatomic sites, which, the authors note, may be due to their polygenic risk score only accounting for a limited variety of phenotypes. Additional limitations include the retrospective nature of the study, relatively smaller control cohort, as well as younger age of the Australian cohort.

These findings have the potential to improve patient care and counseling by improving dermatologists' understanding of melanoma pathogenesis. Future studies should endeavor to study additional anatomical sites (palms, soles, nails) across more diverse racial and ethnic populations to improve generalizability of findings and how sun-protective measures and clothing differentially impact melanoma pathogenesis.

References

1. Day CL Jr, Lew RA. Malignant melanoma prognostic factors 2: the subsite concept. J Dermatol Surg Oncol. 1983;9(7):525-526. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1524-4725.1983.tb00848.x
2. Day CL Jr, Mihm MC Jr, Sober AJ, et al. Predictors of late deaths among patients with clinical stage I melanoma who have not had bony or visceral metastases within the first 5 years after diagnosis. J Am Acad Dermatol. 1983;8(6):864-868. https://linkinghub.elsevier.com/retrieve/pii/S0190-9622(83)80018-8
3. Sober AJ, Day CL Jr, Fitzpatrick TB, et al. Factors associated with death from melanoma from 2 to 5 years following diagnosis in clinical stage I patients. J Invest Dermatol. 1983; 80 Suppl:53s-55s.

Abstract 

BACKGROUND

Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops.

OBJECTIVES

We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk.

METHODS

We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls.

RESULTS

When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites.

CONCLUSIONS

We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.

The British Journal of Dermatology

Risk Factors for Melanoma by Anatomical Site: An Evaluation of Aetiological Heterogeneity

Br J Dermatol 2020 Dec 03;[EPub Ahead of Print], R Laskar, A Ferreiro-Iglesias, DT Bishop, MM Iles, PA Kanetsky, BK Armstrong, MH Law, AM Goldstein, JF Aitken, GG Giles, Australian Melanoma Family Study Investigators; Leeds Case-Control Study Investigators; HA Robbins, AE Cust 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
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