The Laterality of Skin Cancer

J Clin Aesthet Dermatol. 2022;15(12):38–39.

by Jacob M. Hands, BA; Lawrence S. Moy, MD; and Paul K. Shitabata, MD

Mr. Hands is with The George Washington University School of Medicine and Health Sciences in Washington, D.C. Dr. Moy is with South Bay Institute of Clinical Research in Manhattan Beach, California. Dr. Shitabata is with Harbor-UCLA Dermatology, David Geffen School of Medicine at UCLA in Los Angeles, California. 

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.

The finding of a laterality bias in skin cancer incidence remains unresolved in the current literature. Currently, it is thought that there exists a left-sided bias in skin cancer incidence, and that this phenomenon arises from various risk factors, chief among them being driver’s side exposure to ultraviolet irradiation.^1–2 However, the validity of this finding has been debated. We report results from a cohort of 397 subjects presenting to a primary dermatology clinic in Los Angeles, California, for evaluation of a suspected skin malignancy. All subjects that were included (N=397) received a diagnosis (664) of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), or melanoma. 

The laterality of suspicious lesions were recorded (Table 1). A multivariate regression was generated adjusted for age, sex, and site of the lesion to evaluate the significance of laterality in the pathogenesis of cutaneous malignancy. Our findings revealed that neither BCC (-0.045, 95% CI [-0.12 to 0.03]; p=0.25, Table 2), nor SCC (-0.02, 95% CI [-0.10-0.06]; p=0.65, Table 3) were significantly more likely to appear on the subject’s left or right relative to melanoma. Melanoma, however, was significantly more likely to appear on the subject’s right side with respect to BCC and SCC (0.19, 95% CI [0.07 to 0.32]; p=0.003, Table 2). Subsequent one sample t-testing confirmed that Melanoma was significantly more likely to be diagnosed on the subject’s right side (Mean=1.64 + 0.06, t-value=2.25, p=0.03, Table 3). Though BCC did not achieve lateral significance when male and female subjects were evaluated jointly, when isolated to male subjects, BCC appeared significantly more likely to present on the subject’s left side (mean=1.4 + 0.3, t-value =-2.21, p=0.03, Table 4). Similarly, melanoma’s highly significant bias towards right-sided presentation was driven by its right-sided appearance in male subjects (mean= 1.68 + 0.07, t-value=2.41, p=0.02).

The significance of increased left-sided incidence in the presentation of skin cancer is, in fact, a contested finding, with several authors reporting contradictory results.^1-5 Our findings contrast with those of previous authors who have document marked left-sided incidence with respect to BCC and SCC, and melanoma incidence.^1,2 BCC and SCC were not significantly more likely to appear on the subject’s left or right side when controlling for sex, age, and the site of malignant presentation. However, in males, BCC appeared more likely to appear on the subject’s left side. We observed a right-sided bias in cases of melanoma, especially among male subjects which appears to be novel. It is unlikely that this result is due to chance; standard errors were robust, random effects were employed. 

Explanations for the increased incidence of left-sided cases of skin cancer tend to invoke automotive driving behaviors^3,4 and constitutional factors such as sex-specific differences in nevus colonization.^3,5 It is assumed that seating (driver’s versus passenger’s side) significantly contributes to disparate ultraviolet exposure in drivers and passengers alike, though analyses are sparse and, notably, many have failed to demonstrate left-sided excess in countries with inverse driver’s seating arrangements.⁵ Sex-specific differences in nevus colonization are reliable and first appear in the course of early adolescence and puberty, with men reporting greater numbers of nevi on the torso and females reporting greater numbers of nevi on the legs.^3,6,7 While behavioral and genetic risk factors have been proposed as contributory, a recent analysis of 1,512 subjects concluded that approximately 70 percent of the variability in nevi distribution in females could be attributed to genetic factors.^6,7 In particular, the effect of sex chromosomes on the genesis and distribution of nevi is pronounced with certain groups, such as those with Turner’s syndrome, reporting greater numbers of nevi than unaffected controls.^6,7 We remark that sex-specific differences in neural crest function may also be considered in the context of laterality bias and site in the presentation of skin cancer. Neural crest cells that arise from embryonic germ layers control the proliferation and subsequent distribution of melanocytes—a pattern that appears stable into adulthood. Accordingly, identical sex-dependent mutations in the neural crest (termed neurocristopathies) impact melanoma incidence in males and females differently.^6,7 Sex-specific differences in neural crest function is a heretofore unexplored hypothesis that we advocate should be tested alongside suspicion of laterality bias in skin cancer, especially melanoma.

Of note, while an overall finding of a right-sided bias in the presentation of melanoma is novel, others have specifically demonstrated that invasive cases of melanoma exhibit right-sided predominance as well as melanoma among certain sub-groups, such as women over 50.⁴ In fact, this cohort featured a substantial share of invasive to in-situ cases–(approximately 41% invasive cases of melanoma). The possibility invasion may be related to laterality is a finding that merits further attention. Thus, we speculate that this particular result may be explained by the composition of our cohort and the severity of cases upon presentation.

Central limitations of our findings include the absence of information pertaining to family skin cancer history, race, sun-related behaviors, the location of the cohort, and limited sample size. 

Acknowledgments

The authors would like to thank Grace Miller, for data gathering, preliminary data analysis, and records formatting, as well as Rahmi Çemen, PhD, for statistical oversight and design suggestion. 

References

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