Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors

Abstract

(2015) Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors, Dermato-Endocrinology, 7:1, e1004018, DOI: 10.1080DOI: 10. /19381980.2014 For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find b HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D 3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D 3 and possibly viral infection.

All sites but skin cancer incidences analyzed worldwide by sex, age, and skin type over time (1955-2007), advancing age, and UVB dose reveals important carcinogenic drivers

“…We previously described the Fitzpatrick skin type [58] designations for the populations in the different countries, the latitudes and UVB doses used, and the details of the method of analysis. [12,51,52] Quality control involved an assessment of the validity, completeness, and comparability of the incidence data, the details of which IARC provides online. [57] The IARC cancer incidence data includes all tumor stages, thicknesses, histological subtypes, and body site locations.…”

“…The only country added into this analysis that was not included in our previously published studies [51,52] is Thailand where we analyzed over time, advancing age, and UVB doses for skin type III-IV populations in Bangkok (13. …”

“…[49] Persistent HPV infection is responsible for over 90% of cervical and anal cancers, around 70% of vulvar, vaginal, and oropharynx cancers, and over 60% of penile cancers the rates of which vary by race and ethnicity: Hispanics and blacks > whites > Asian and Pacific Islanders. [50] If a cancer is steadily increasing over time beyond what genetic inheritance predicts, like cutaneous malignant melanoma, [51,52] that may indicate HPV infection is involved because its incidence has been documented to be increasing dramatically over recent decades in Europe [53] and in the United States (US). [7] However, depending on the type of cancer, the increasing incidence over time could be due to the spread of other infectious diseases like herpesviruses (EBV and KSHV), polyomaviruses (SV40, MCV, BK, and JCV), hepadnaviruses (HBV), flaviviruses (HCV), defective viruses (HDV), retroviruses (HTLV-I, HTLV-II, HIV-1, HIV-2, HERV-K, and XMRV), and bacteria, like H. pylori, S. typhi, S. bovis, Bartonella, and C. pneumonia, as well as protozoa, like P. falciparum, and parasites like trematodes, like S. haematobium, S. japonicum, S. mansoni, O. viverrini, O. felineus, and C. sinensis.…”

“…[7] However, depending on the type of cancer, the increasing incidence over time could be due to the spread of other infectious diseases like herpesviruses (EBV and KSHV), polyomaviruses (SV40, MCV, BK, and JCV), hepadnaviruses (HBV), flaviviruses (HCV), defective viruses (HDV), retroviruses (HTLV-I, HTLV-II, HIV-1, HIV-2, HERV-K, and XMRV), and bacteria, like H. pylori, S. typhi, S. bovis, Bartonella, and C. pneumonia, as well as protozoa, like P. falciparum, and parasites like trematodes, like S. haematobium, S. japonicum, S. mansoni, O. viverrini, O. felineus, and C. sinensis. [54] In previous studies, we analyzed cutaneous malignant melanoma over time all over the world [51] and also over personal UVB dose in Europe [52] and found an exponential increase in the incidence from 1955 to 2007 for only people of European ancestry. We speculated a viral infection like HPV might be involved because the rate only began to increase significantly over time, and increased with decreasing personal UVB dose only after 1960, implying increasing time indoors causing low levels of vitamin D 3 may be promoting infection.…”

“…We speculated a viral infection like HPV might be involved because the rate only began to increase significantly over time, and increased with decreasing personal UVB dose only after 1960, implying increasing time indoors causing low levels of vitamin D 3 may be promoting infection. [52] Vitamin D 3 has been gradually decreasing over several decades, as noted by the increasing trend of its inversely related parathyroid hormone. [55] Our recent analysis of melanoma incidences around the world provided evidence that HPV persists in immune privileged androgenic hair follicles where melanocytes, keratinocytes, and stem cells reside.…”