In a recent study, reviewed in this issue of The ASCO Post, Li et al present data from two long- term prospective studies—the Physicians Health Study (PHS, from 1982 to 1998), and the Health Professionals’ Follow-up Study (HPFS, from 1986 to 2010)—both of which suggest a strong association between prostate cancer and risk of melanoma.1
Both studies sought to monitor medical history and lifestyle practices. The PHS was a randomized, double-blind, placebo-controlled trial with annual follow-up for the prevention of cancer and cardiovascular disease. The HPFS used self-reported questionnaires biennially, whereas the PHS incorporated self-reporting of prostate cancer, at which time immediate medical records and pathology reports were requested.
Androgens and Acne
The Li et al study introduces and attempts to support the hypothesis that not only is there a strong association between prostate cancer and the development of melanoma, but there is also an underlying association between androgens and acne as a precursor of prostate cancer. The authors’ prior work has suggested that severe teenage acne, which may be a surrogate for high androgen activation, could indirectly be a risk factor for melanoma, thereby leading to an association between melanoma and prostate cancer.
Analyses of prostatectomy specimens have shown chronic inflammatory changes that may serve as a precursor for the development of prostate cancer. The inflammatory changes have been associated with infiltration by intraprostatic Propionibacterium acnes and subsequently may have led to the development of acne vulgaris in youth.
Questionnaires that indicated the self-reported use of tetracycline for the treatment of acne for 4 or more years provided data that an association of chronic tetracycline use for acne could lead to a higher risk of prostate cancer. This incorporated a constellation of lifestyles that included increased risk of sun exposure with blistering facial sunburns, increased alcohol consumption, less calcium consumption, and greater alcohol consumption in youth. While not deemed an epiphenomenon, the strength of this association has never been conclusively borne out.
Ironies and Uncertainties
The current study reviews multiple aspects of the HPFS and PHS participants including the personal history of prostate cancer. In the 747,176 person-years reported, 5,091 prostate cancers and 539 melanomas were identified, suggesting that a personal history of prostate cancer was significantly associated with risk of melanoma (hazard ratio = 1.83, 95% confidence interval = 1.32–2.54).
While the studies presented were prospective, and suggested a strong association of melanoma with prostate cancer, there is still concern that other factors may play a pivotal role in the association. Among the driving forces in prostate cancer growth is the androgen receptor, while melanoma has BRAF mutations as its main focus for therapeutic targeting.
Melanoma is deemed a disease of chronic and severe sun exposure. It is of interest that patients from Scandinavia who experienced markedly fewer months of sunlight were found to be vitamin D deficient and therefore believed to be at higher risk for prostate cancer. In a study by Moan et al,2 people living in southern latitudes and who made more vitamin D from sun exposure were less likely to die from those cancers than were the northern latitude residents. Ironically, many men who retire often do so in sunny climes where the sun exposure is high, often promoting near-normal to normal vitamin D levels, but these men still develop prostate cancer in addition to melanoma.
It remains unclear as to the stage of the prostate cancer during which melanoma developed in the Li et al report, whether these men were at castrate levels of testosterone for their prostate cancer treatment, what stage the melanoma was at diagnosis, and how many of these patients died of their melanoma rather than of their prostate cancer. The authors acknowledge limitations in the detail of the prostate cancer treatment.
Another point of interest is the fact that the PHS revealed that more than two-thirds of the nearly 15,000 study participants had suboptimal blood levels of vitamin D in the winter and spring. Among men who developed prostate cancer, those with low levels of vitamin D (aged ≥ 65 years) were more likely to have an aggressive form of the disease.
Broad Implications
The authors provide strong statistical data based on two large, well-established, long-term cohorts. The speculation that androgens can play a potential role in melanoma and may contribute to its association with prostate cancer is tantalizing.3
The authors point toward the fact that patients with an androgen imbalance during prostate carcinogenesis might be at greater risk for melanoma development. While there exists an increased risk of melanoma in patients with prostate cancer, the converse association did not appear to hold true.
The implications for this study are broad and certainly have potential public health impact. Further characterization of genetic characteristics in these cases will likely help determine whether there is a commonality between the two diseases. Even if these observations are not confirmed, it nevertheless brings awareness of how these associations can impact lifestyle, health maintenance, and treatments. ■
Disclosure: Dr. Slovin reported no potential conflicts of interest.
References
1. Li W-Q, Qureshi AA, Ma J, et al: Personal history of prostate cancer and increased risk of incident melanoma in the United States. J Clin Oncol 31:4394-4399, 2013.
2. Moan J, Porojnicu AC, Dahlback A, et al: Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure. Proc Natl Acad Sci USA 105:668-673, 2008.
3. Rampen FH, Mulder JH: Malignant melanoma: An androgen-dependent tumour? Lancet 1(8168 pt 1):562-564, 1980.
