Int J Cancer: Does the number of pigmented moles correlate with cancer risk?

Melanocytic nevi are benign skin tumors composed of localized overgrowths of melanin-forming cells
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The tendency for moles to develop is genetically determined, although childhood sun exposure clearly plays a role

Several large cohort studies have reported positive associations between higher mole counts and cancers including breast and thyroid
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A recent study found an overall association between mole number and medical cancer (HR for 15 or more moles vs.

Despite hypotheses linking moles and other cancers, whether the association between moles and cancer reported in observational studies represents a true relationship, or is due to factors associated with mole count and cancer (eg, clinical surveillance) due to bias or confusion remains unclear
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Genome-wide association studies have successfully identified numerous genomic regions, including variants in CDKN2A and phospholipase A2 group VI (PLA2G6)

We calculated polygenic risk scores (PRs) for mole counts using individual-level data from the UK Biobank (n=394306) and the QSkin cohort (n=17427)
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Logistic regression analysis was performed on the effects of age, sex, and the top five principal components, evaluating the association between moles, PR, and each tumor site

Table 1 Number of cancer cases and their prevalence in the UK Biobank and QSkin cohorts

 

Figure 1 Association between genetically predicted mole counts and individual or overall cancer risk, according to the quartile of mole count, polygenic risk score (PRS), using individual-level data from the UK Biobank
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Any cancer excludes skin cancer; blood diseases includes leukemia and lymphoma; head and neck excludes lip cancer; basal cell carcinoma; squamous cell carcinoma, squamous cell carcinoma of the skin

Figure 2 Association of genetically predicted mole counts with individual or overall cancer risk according to mole count quartile polygenic risk score (PRS) using individual-level data from the QSkin cohort
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Any cancer excludes skin cancer; blood cancer includes leukemia and lymphoma; head and neck excludes lip cancer; BCC, basal cell carcinoma; SCC, squamous cell carcinoma of the skin

In conclusion, we found a significant association between high genetic risk of moles and skin cancer, but no evidence of an association between high genetic risk moles and cancer risk
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We reasoned that the association between freckles count and cancer reported in earlier observational studies is unlikely to be causal

Source: Dusingize JC, Law MH, Pandeya N, Genetically determined cutaneous nevi and risk of cancer.

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