PCa & Melanoma.

[pjoshea13]

Interesting new study below. [1]

I would not have expected a PCa/Melanoma association. The diseases have opposite associations with lattitude (i.e. with sun / vitamin D exposure.)

There are 88 PubMed hits for <prostate[title] melanoma[title]>.

There are a surprising number for metastatic melanoma to the prostate, dating from 1953. But, ignoring those, an association was observed in the Health Professionals' Follow-Up Study [HPFS] [2] in 2013. The rationale for the study was:

"Personal history of severe acne, a surrogate for higher androgen activity, has been associated with an increased risk of prostate cancer (PCa), and one recent study indicated that severe teenage acne was a novel risk factor for melanoma."

The study found "that patients with PCa had a significantly increased risk of melanoma" - twice the risk.

There are three overdiagnosed cancers in men: prostate, thyroid & melanoma. i.e. where 'overdiagnosed' means 'histologically malignant but biologically benign'. However, the authors state that the association could not be explained by greater medical scrutiny.

It didn't take long before testosterone became the smoking gun [3]:

"the possibility of high levels of endogenous androgens promoting not only prostate cancer, but also increased risk of melanoma"

But now, in the new study from Cedars-Sinai [1], we have a more plausible explanation - loss of testosterone:

"In men, the incidence of melanoma rises rapidly after age 50, and nearly two thirds of melanoma deaths are male. The immune system is known to play a key role in controlling the growth and spread of malignancies, but whether age- and sex-dependent changes in immune cell function account for this effect remains unknown. Here, we show that in castrated male mice, neutrophil maturation and function are impaired, leading to elevated metastatic burden in two models of melanoma. Replacement of testosterone effectively normalized the tumor burden in castrated male mice. Further, the aberrant neutrophil phenotype was also observed in prostate cancer patients receiving androgen deprivation therapy, highlighting the evolutionary conservation and clinical relevance of the phenotype. Taken together, these results provide a better understanding of the role of androgen signaling in neutrophil function and the impact of this biology on immune control of malignancies."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/322...

[2] ncbi.nlm.nih.gov/pmc/articl...

[3] pubmed.ncbi.nlm.nih.gov/245...

[noahware]

"Replacement of testosterone effectively normalized the tumor burden in castrated male mice. "

A question would be, if the more plausible explanation is loss of testosterone, is the mechanism of action related to the actual loss of testosterone, or could it be the loss of estrogen that is a direct effect of a loss of testosterone? Would replacing estrogen alone normalize the tumor burden?

(Do male mice aromatize testosterone into estrogen the way men do?)

[Hidden]

I cringe when doctors jump to testosterone causation. I have this image of sickly little guys snickering at the thought of removing testosterone from a normal man.

Rant over (for now). I wonder if lack of testosterone or high testosterone is the root. Or if it DHT or estrogen (as noahware points out), or higher cholesterol or prolactin or.... So, is testosterone simply a victim of correlation? Or is it real causation and does changing other hormones have no affect?

[j-o-h-n]

I know this info is old news.... but I do have a lung melanoma........ (from a melanoma on my neck).... Fighting it with Keytruda... that's working (at MSKcc)...

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 04/04/2020 12:07 AM DST

[timotur]

Thanks for posting this study, I’ve noticed a few aberrant dark spots showing up recently in different odd places— leg, chest, neck, after one year on ADT. Need to see a Derm.

[2dee]

I'm BRCA2 mutated.

Melanoma removed in 1984 and 2019.

Had Basil Cell and Squamous removed a few times before APCa Dx stage4 in 2018.

On Lupron since 2018.

I don't think one caused the other, rather I was just at a much greater genetic risk. Luck of the draw.

2Dee

[EdBar]

I was dx with melanoma about a year after being dx with PCa. Fortunately it was in-situ meaning it hadn’t spread yet.

Turns out I have a CHEK 2 mutation that makes me more inclined to get both.

Ed

[Hidden]

I recall reading that there was a correlation between skin cancer of any type and the propensity to develop prostate cancer. I've had plenty of basal and squamous cell cancers treated, mostly on my face. Of course that leads to another thought. Black men seem most prone to prostate cancer and I would think that they are least prone to skin cancers.

[pjoshea13 in reply to Hidden]

The higher incidence of PCa in African-Americans might be explained by lower levels of vitamin D:

"A high percentage of American blacks have suboptimal blood levels of 25(OH)D and levels that are well below those of American whites. Poor vitamin D status may increase the risk of blacks as well as others for osteoporosis, cardiovascular disease, cancer, diabetes, and other serious chronic conditions."

academic.oup.com/jn/article...

"Skin cancer is rare in blacks compared with whites in the United States. The most common form is squamous-cell carcinoma, not basal-cell carcinoma, as it is in whites. Sunlight does not appear to be an important etiologic factor in skin cancer in blacks, as most lesions occur on covered areas."

pubmed.ncbi.nlm.nih.gov/304...

-Patrick

[lewicki in reply to pjoshea13]

This is very interesting. I have had numerous basil cell cancer removed from face and chest Had melanoma on right leg and left forearm three and 7 years ago. Blamed it on red blond hair and north Europe parents. Prostate cancer 21 years ago at age 59. So will a huge testosterone treatment work in killing the prostate cancer? who knows. Perhaps the farmers juicing the cows for more milk in the 40,s and 50,s caused all of this.