Untangling the Most Probable Role for Vitamin D\u3csub\u3e3\u3c/sub\u3e in Autism

Recent studies indicate an important role for vitamin D3 in autism spectrum disorder (ASD), although its mechanism is not completely understood. The most puzzling aspect of ASD is that identical twins, who share identical DNA, do not have 100% concordance rates (∼88% for identical and ∼31% for fraternal twins). These findings provide major clues into the etiology: ASD must involve an environmental factor present in the prenatal milieu that both identical twins are not always exposed to because they do not always share it (i.e., placentas). Combined with the exponential increasing rates of ASD around the world, these observations suggest a contagious disease is probably transferred to the fetus via the placenta becoming infected by a cervical virus. Vitamin D3 boosts immune responses clearing viral infections and increases serotonin and estrogen brain levels. Here we review the different roles and untangle the most probable one vitamin D3 plays in ASD

Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

The incidence of cutaneous malignant melanoma (CMM) has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290–320 nm) exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321–400 nm) passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to ~50°N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide

Worldwide Cutaneous Malignant Melanoma Incidences Analyzed by Sex, Age, and Skin Type Over Time (1955–2007): Is HPV Infection of Androgenic Hair Follicular Melanocytes a Risk Factor for Developing Melanoma Exclusively in People of European-Ancestry?

The cutaneous malignant melanoma (CMM) incidence has been increasing in an exponential manner in certain populations around the world for over 7 decades. To help illuminate the etiology, we performed worldwide temporal (1955–2007) CMM incidence analysis by sex, age (0–14, 15–29, 30–49, 50–69, 70–85+), and skin type on 6 continents using data from the International Agency for Research on Cancer. We observe an exponential increase in the CMM incidence over time and an increase of about 2 orders of magnitude between age groups 0–14 and 15–29 exclusively in European-ancestry populations around the world independent of skin type (I–III or III–IV). Other populations like the Chinese (III-IV) had much lower CMM incidences that either remained stable or temporally decreased but did not display a dramatic increase between the youngest age groups. The dramatic increase in the incidence between the youngest age groups found only in European-ancestry populations suggests one of the most important risk factors for CMM may be developing androgenic hair, the occurrence of which appears to correlate with the distribution of CMM over male and female body sites. Besides that potential new risk factor, the increasing CMM incidence with increasing age, known not to be from cumulative UV doses, may be associated with age-related changes to skin, i.e., thinning epidermis causing lower vitamin D3 levels, and hair, i.e., whitening from higher reactive oxygen species. The temporal exponential increasing CMM incidence in European-ancestry populations may be due to Human Papilloma Virus infection of follicular hair melanocytes, found in CMM biopsies

Pharyngeal and Cervical Cancer Incidences Significantly Correlate with Personal UV Doses Among Whites in the United States

Because we found UV-exposed oral tissue cells have reduced DNA repair and apoptotic cell death compared with skin tissue cells, we asked if a correlation existed between personal UV dose and the incidences of oral and pharyngeal cancer in the United States. We analyzed the International Agency for Research on Cancer\u27s incidence data for oral and pharyngeal cancers by race (white and black) and sex using each state\u27s average annual personal UV dose. We refer to our data as ‘white’ rather than ‘Caucasian,’ which is a specific subgroup of whites, and ‘black’ rather than African-American because blacks from other countries around the world reside in the U.S. Most oropharyngeal carcinomas harboured human papilloma virus (HPV), so we included cervical cancer as a control for direct UV activation. We found significant correlations between increasing UV dose and pharyngeal cancer in white males (p=0.000808) and females (p=0.0031) but not in blacks. Shockingly, we also found cervical cancer in whites to significantly correlate with increasing UV dose (p=0.0154). Thus, because pharyngeal and cervical cancer correlate significantly with increasing personal UV dose in only the white population, both direct (DNA damage) and indirect (soluble factors) effects may increase the risk of HPV-associated cancer

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

Because we observed increasing incidences over time, advancing age, higher estrogen levels, decreasing UVB (290-315 nm) doses, or lower vitamin D3, and Human Papillomavirus hiding in immune-privileged sites of hair follicles play roles in melanoma, we wondered if the majority of cancers might have similar carcinogenic drivers. To investigate this possibility, we performed worldwide analysis of all sites but skin cancer over time (1955-2007), advancing age, and UVB doses for males and females with all skin types and ages (0-85+) and in five age groups using IARC data. To investigate Human Papillomavirus’s role, we analyzed the incidences of breast, prostate, and colon cancers in a developed country with European ancestry (New Zealand) having high amounts of androgenic hair and a developing country with Asian ancestry (India) having low amounts of androgenic hair. To potentially add epidemiology to the already established role of estrogen in cancer, we analyzed males and females in various countries around the world using the incidence of breast cancer (\u3e 70 yr.) as an established indicator of estrogen levels. The analysis reveals cancer incidences are steadily increasing over time in developed but not developing countries regardless of skin type. Only US white, but not black, breast, prostate, and colon cancer incidences in the oldest age group significantly decreased with increasing UVB dose suggesting a role for vitamin D3. The data suggests the carcinogenic drivers in many cancers are estrogen, increasing age (or reactive oxygen species), decreasing vitamin D3 levels, and persistence of Human Papillomavirus infection in immune-privileged sites

Worldwide Cutaneous Malignant Melanoma Incidences Analyzed by Sex, Age, and Skin Type Over Time (1955–2007): Is HPV Infection of Androgenic Hair Follicular Melanocytes a Risk Factor for Developing Melanoma Exclusively in People of European-Ancestry?

The cutaneous malignant melanoma (CMM) incidence has been increasing in an exponential manner in certain populations around the world for over 7 decades. To help illuminate the etiology, we performed worldwide temporal (1955–2007) CMM incidence analysis by sex, age (0–14, 15–29, 30–49, 50–69, 70–85+), and skin type on 6 continents using data from the International Agency for Research on Cancer. We observe an exponential increase in the CMM incidence over time and an increase of about 2 orders of magnitude between age groups 0–14 and 15–29 exclusively in European-ancestry populations around the world independent of skin type (I–III or III–IV). Other populations like the Chinese (III-IV) had much lower CMM incidences that either remained stable or temporally decreased but did not display a dramatic increase between the youngest age groups. The dramatic increase in the incidence between the youngest age groups found only in European-ancestry populations suggests one of the most important risk factors for CMM may be developing androgenic hair, the occurrence of which appears to correlate with the distribution of CMM over male and female body sites. Besides that potential new risk factor, the increasing CMM incidence with increasing age, known not to be from cumulative UV doses, may be associated with age-related changes to skin, i.e., thinning epidermis causing lower vitamin D3 levels, and hair, i.e., whitening from higher reactive oxygen species. The temporal exponential increasing CMM incidence in European-ancestry populations may be due to Human Papilloma Virus infection of follicular hair melanocytes, found in CMM biopsies

Cutaneous Malignant Melanoma Incidences Analyzed Worldwide by Skin Type over Advancing Age of Males and Females: Evidence Estrogen and Androgenic Hair are Risk Factors

We previously analyzed cutaneous malignant melanoma (CMM) incidences worldwide by sex, age, and Fitzpatrick skin type over time (1955-2007) and found only European-ancestry populations have exponential increasing incidences and about a 2-log increase in the risk between the youngest age groups (0-14 and 15-29 yr). We proposed the increasing incidence over time may be from the spread of Human Papilloma Virus (HPV) found in CMM biopsies, and that the 2-log incidence increase between the youngest age groups might be from developing androgenic hair. The increasing incidence with age may be from white hairs transmitting UV radiation to follicular melanocytes. Here we analyzed CMM incidences over the advancing age of males and females of every skin type (I-VI) worldwide. We found only European-ancestry females have a linear increase in their CMM risk while males of all races have a power function increase in their risk with advancing age. We propose the gradual loss of HPV-infected androgenic follicles with advancing age of only European-ancestry females during and after menopause significantly reduces their CMM risk compared to all males who do not have significant estrogen loss and consequent loss of androgenic hair with advancing age. All other races have females with significantly lower amounts of androgenic body hair so that its loss with advancing age is not significant. These results combined with those in the literature and our previous findings showing CMM has been increasing over time, suggests estrogen synergizes HPV infection of androgenic follicular melanocytes significantly increasing the risk for getting CMM

Cutaneous Malignant Melanoma Incidences Analyzed Worldwide by Sex, Age, and Skin Type over Personal Ultraviolet-B Dose Shows No Role for Sunburn but Implies One for Vitamin D\u3csub\u3e3\u3c/sub\u3e

Because the incidence of cutaneous malignant melanoma (CMM) was reported to increase with increasing terrestrial UVR (290–400 nm) doses in the US back in 1975 and a recent publication showed no association exists with UVR exposure at all, we set out to fully elucidate the role of UVR in CMM. To achieve this goal, we analyzed the CMM incidences over latitude and estimated the average personal UVR dose in the US and numerous countries (\u3e 50) on 5 continents around the world. Using data from the International Agency for Research on Cancer in 2005, we performed worldwide analysis of CMM over UVR dose by sex, age group (0–14, 15–29, 30–49, 50–69, 70–85+) and Fitzpatrick skin types I-VI. Surprisingly, increasing UVR doses, which represent erythemally-weighted doses comprised primarily of UVB (290–315 nm) radiation, did not significantly correlate with increasing CMM incidence for people with any skin type anywhere in the world. Paradoxically, we found significant correlations between increasing CMM and decreasing UVB dose in Europeans with skin types I-IV. Both Europeans and Americans in some age groups have significant increasing CMM incidences with decreasing UVB dose, which shows UVB is not the main driver in CMM and suggests a possible role for lower cutaneous vitamin D3 levels and UVA (315–400 nm) radiation. CMM may be initiated or promoted by UVA radiation because people are exposed to it indoors through windows and outdoors through some sunscreen formulations. Thus, our findings may explain why some broad-spectrum sunscreen formulations do not protect against getting CM