Melanoma predilection for the lower limbs of women compared with men

The lower limb is a common site for melanoma in women, but the reason for this is not fully understood. To investigate this phenomenon in more detail, we assessed the specific subsites of primary melanoma occurring on the lower limbs of females compared with males across age groups. In a records-based study at an oncology hospital in north-west of England, among an unselected sample of patients with primary invasive melanoma treated between 2002-2015, information was collected on patient age at diagnosis, sex, and co-morbidities, and the tumor thickness and anatomical subsite (thigh, lower leg, foot for lower limb). Of a total sample of 1,522 patients, 316 (227, 72% female) had lower limb melanoma. The most common subsite was lower leg (142 cases with F:M ratio =3.74), followed by thigh (55 cases with F:M = 1.83) and feet (30 cases with F:M = 1.15). At ages <40 years the odds of thigh to foot melanoma was 20 times higher in females than in males (OR 20.0, 95% CI 2.6-152.6) and 7.5 times higher on the lower limb (OR 7.5, 95% CI 1.1-49.2). For ages 40+ years, the odds of females developing thigh melanoma compared to foot melanoma was similar in males versus females (OR 0.8), while the corresponding odds of lower leg melanoma in females versus males remained significantly increased at ages 40-59 and 60+ (OR 4.2 and 2.8 respectively). Our study demonstrates the female predilection for lower limb melanoma persists over most but not all subsites.However, there is heterogeneity in the female to male occurence of lower limb melanoma across subsites and at different ages, which may be linked to relative influence of genetic and environmental risk factors.