PLOS Medicine has simultaneously published two new studies finding that moles – or cutaneous nevi – may be a predictor of breast cancer. The two teams – from the US and France – find that women with a greater number of moles are more at risk of developing breast cancer.
Moles are benign skin tumors that occur more frequently in light- than dark-skinned people. Individuals can be born with moles or they may acquire them throughout life. Twin studies have shown that there is a 40-80% genetic influence over the extent to which people develop moles, and childhood sun exposure is also thought to be a contributing factor.
Some studies have shown that women with a greater number of moles are more at risk from hormone-influenced conditions such as endometriosis, leiomyoma and thyroid diseases.
The number of moles that a person might acquire – as well as melanoma risk – has also been associated with the CDKN2A gene. Inactivation of this gene – which is implicated in cell cycle regulation – is associated with breast cancer.
Therefore, the team of French researchers – from the Institut National de la Santé et de la Recherche Médicale (INSERM) – decided to investigate whether number of moles is associated with breast cancer risk.
To do this, they analyzed data from the E3N Teachers’ Study Cohort in France, which followed 89,902 women for 18 years. The women were asked to report whether they had no, a few, many or very many moles.
Women reporting having “very many” moles were found to have a 13% higher risk of breast cancer than women reporting having no moles. However, when the results were adjusted for known breast cancer risk factors, the association was no longer statistically significant. These confounding risk factors – such as benign breast disease or family history of breast cancer – are themselves associated with mole number.
In their study, the authors write that “a causal relationship between number of nevi and breast disease risk seems unlikely.” However, the researchers speculate that the same genetic factors could contribute to development of both breast cancer and moles. Alternatively, the researchers suggest that levels of sex hormones may influence both development of moles and breast cancer.
The hormonal influence on moles and breast cancer was further explored by the American team. The authors – from Indiana University and Harvard University – observed that moles usually become bigger or darker during pregnancy, which suggests a possible link between moles and hormones.
This team analyzed data from the US Nurses’ Health Study – a cohort of 74,523 female nurses, followed for 24 years. Participants were asked to report the number of moles greater than 3 mm on their left arm.
The researchers found that women reporting 15 or more moles were 35% more likely to be diagnosed with breast cancer than those reporting no moles. From this, they calculated that women with 15 or more moles had an absolute risk of 11.4% of developing breast cancer, compared with an absolute risk of 8.48% in women with no moles.
Within a subgroup, the team also tested a possible association between elevated hormone levels and moles and breast cancer. They write:
“We further found that postmenopausal women with more cutaneous nevi had higher levels of plasma total and free testosterone and estradiol, and that the number of cutaneous nevi was associated with increased risk of breast cancer only among [estrogen receptor]-positive tumors, suggesting that a hormonal effect underlies this association.”
Although both studies find an association between breast cancer and number of moles, neither study is able to clearly identify the mechanism that drives this association. The studies do raise the possibility of number of moles being used to predict breast cancer risk, but they are unable to give an indication of how reliable this test would be.
Also, as the studies mainly observed white participants, it may not be possible to generalize the findings of the studies to non-white women.