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A prospective study of incident squamous cell carcinoma of the skin in the nurses' health study.

BACKGROUND: Few epidemiologic studies are available that quantify the magnitude of the risk of squamous cell carcinoma (SCC) of the skin associated with sun exposure and related factors such as skin type. In addition, several studies have found an association between cigarette smoking and SCC. PURPOSE: We prospectively examined the risk of developing SCC in relation to phenotype and the effects of sun exposure, as well as to cigarette smoking and other factors, during 8 years of follow-up in a cohort of 107,900 predominantly white women aged 30-55 years at base line in 1976. METHODS: Questionnaires regarding medical history and health-related variables were sent to Nurses' Health Study participants every 2 years, beginning in 1976. Information on constitutional factors (natural hair color, childhood and adolescent tendency to sunburn and tan, and lifetime number of severe sunburns), lifestyle factors (regular time spent outdoors in the summer and sunscreen use), the state lived in at birth and at ages 15 and 30 years, and cigarette smoking habits were ascertained by questionnaire. A total of 197 women with first-incident, histologically confirmed, invasive SCCs that were diagnosed from 1982 to 1990 were included in this analysis. Multivariate analysis using proportional hazards models was used to calculate the relative risks (RRs) and corresponding 95% confidence intervals (CIs), with adjustment for confounders. RESULTS: The risk of SCC was increased in women living in California (RR = 1.8; 95% CI = 1.3-2.6) and Florida (RR = 2.1; 95% CI = 1.1-3.9) at base line, compared with those living in the northeastern states. This risk was higher for women living in those states at birth and at 15 years of age (RR = 2.5; 95% CI = 1.4-4.4 for California and RR = 3.0; 95% CI = 0.7-1.2 for Florida). Red (RR = 2.0; 95% CI = 1.1-3.7) and light brown (RR = 1.7; 95% CI = 1.2-2.4) hair colors were associated with an increased risk of SCC, compared with dark brown hair. After adjusting for the number of sunburns, women who tended to burn after 2 or more hours of sun exposure as children had a slightly higher risk of SCC than those who never burned (RR = 1.5; 95% CI = 0.9-2.5 for burn and RR = 1.1; 95% CI = 0.6-2.0 for painful burn), although the actual number of severe burns appeared to be a more important factor (RR = 2.4; 95% CI = 1.5-4.0 for six or more burns). Finally, current cigarette smokers showed a 50% increase in the risk of SCC compared with never smokers (RR = 1.5; 95% CI = 1.1-2.1). CONCLUSION: Exposure to the sun leading to sunburn, particularly at early ages, should be avoided to decrease the risk of incident SCC.

Adult↗

Gestational risk factors for Wilms' tumor: results of a case-control study.

Gestational risk factors for Wilms' tumor were investigated in a pair-matched case-control study. Cases who were under 15 years of age at diagnosis during 1970-1983 were identified through the registries of the three main hospitals treating childhood cancer in the greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date, and telephone area code and exchange. Because of a low participation rate among nonwhites, results are reported only for the 88 white matched pairs whose parents were interviewed by telephone. Of the hypothesized risk factors, maternal use of hair-coloring products in the year prior to the index child's birth (odds ratio, 3.6; P = 0.003) and hypertension or fluid retention during pregnancy (odds ratio, 5.0, P = 0.01) were significantly associated with increased risk of Wilms' tumor. Use of hair-coloring products was strongly associated with cases in which Wilms' tumor was diagnosed before 2 years of age (odds ratio, 15; P = 0.001). For two other gestational factors, tea drinking and vaginal infection, the odds ratios were significantly elevated for all cases and the effects were concentrated among the nongenetic cases. Bilateral cases had a significantly higher mean birth weight than did their controls. Older maternal age was significantly associated with the genetic form of Wilms' tumor. Adjustment for possible confounders and consideration of the time interval between the index pregnancy and the interview did not substantially alter the findings.

Female↗

Beauty product-related exposures and childhood brain tumors in seven countries: results from the SEARCH International Brain Tumor Study.

Data from 1218 cases of childhood brain tumors (CBT) diagnosed between 1976 and 1994 and 2223 matched controls from the general population were included in an analysis of maternal beauty product exposure and beauty-related employment in 9 centers in 7 countries. A 50% increased odds ratio (OR) [95% confidence interval (CI) = 1.0-2.1] for CBT was observed among children of mothers who were exposed via personal use of and/or possible ambient contact with beauty products during the 5 years preceding the index child's birth compared with children of mothers never exposed to beauty products during this time period. Overall maternal personal use of hair-coloring agents in the month before or during the pregnancy of the index child's birth was not associated with CBT (OR = 1.0, CI = 0.83-1.3) or with astroglial (OR = 1.1, CI = 0.85-1.4), PNET (OR = 1.0, CI = 0.71-1.5) and other glial subtypes (OR = 1.0, CI = 0.62-1.0). Similarly, no statistically increased ORs or discernable pattern of risk estimates were observed for period of use or for number of applications per year for maternal personal use of hair-coloring agents overall or by histologic type. Among children born on or after 1980, increased ORs for CBT were associated with maternal non-work-related exposure to any beauty products (OR = 2.6, CI = 1.2-5.9), hair-dyes (OR = 11, CI = 1.2-90), and hair sprays (OR = 3.4, CI = 1.0-11). No overall increased OR for CBT was observed among children of mothers employed in beauty-related jobs during the 5 years preceding the index child's birth compared with those who reported no beauty-related employment. In general, other specific beauty product-related exposures were not associated with increased ORs for CBT. Data from our study provide little evidence of an increased risk for CBT with mothers' exposures to beauty products.

Adolescent↗

Graying: gerontobiology of the hair follicle pigmentary unit.

The visual appearance of humans derives predominantly from their skin and hair color. The phylogenetically ancient biochemical [corrected] pathway underling this phenomenon is called melanogenesis and results in the production of melanin pigments in neural crest-derived melanocytes, followed by its transfer to epithelial cells. While melanin from epidermal melanocytes clearly protects human skin by screening harmful ultraviolet radiation, the biologic value of hair pigmentation is less clear. In addition to important roles in social/sexual communication, one potential benefit of pigmented scalp hair in humans may be the rapid excretion of heavy metals, chemicals, toxins from the body by their selective binding to melanin. The hair follicle and epidermal melanogenic systems are broadly distinct, though open. The primary distinguishing feature of follicular melanogenesis, compared to the continuous melanogenesis in the epidermis, is the tight coupling of hair follicle melanogenesis to the hair growth cycle. This cycle appears to involve periods of melanocyte proliferation (during early anagen), maturation (mid to late anagen) and melanocyte death via apoptosis (during early catagen). Thus, each hair cycle is associated with the reconstruction of an intact hair follicle pigmentary unit... at least for the first 10 cycles or so. Thereafter, gray and white hairs appear, suggesting an age-related, genetically regulated exhaustion of the pigmentary potential of each individual hair follicle. Melanocyte aging may be associated with reactive oxygen species-mediated damage to nuclear and mitochondrial DNA with resultant accumulation of mutations with age, in addition to dysregulation of anti-oxidant mechanisms or pro/anti-apoptotic factors within the cells. While the perception of "gray hair" derives in large part from the admixture of pigmented and white hair, it is important to note that individual hair follicles can indeed exhibit pigment dilution or true grayness. This dilution is due to a reduction in tyrosinase activity of hair bulbar melanocytes, sub-optimal melanocyte-cortical keratinocyte interactions, and defective migration of melanocytes from a reservoir in the upper outer root sheath to the pigment-permitting microenvironment close to the dermal papilla of the hair bulb. Animal models with mutations in apoptotic survival factors (e.g. bcl-2) and in melanogenic enzymes (TRP-1) are providing valuable insights into the aging hair pigmentary unit. It is from these and other advances, including our ability to grow hair follicle melanocytes in vitro, that the possibility of reversing canities has been raised. Indeed, it is not too uncommon to see spontaneous repigmentation along the same individual hair shaft in early canities. Moreover, melanocytes taken from gray and white hair follicles can be induced to pigment in vitro. One of the surprising results of pigment loss in canities is the alteration in keratinocyte proliferation and differentiation, providing the tantalizing suggestion that melanocytes in the hair follicle contribute far more that packages of melanin alone. Furthermore, there have been some unconfirmed reports in the literature suggesting that canities may link (although not causally) with more systemic alterations in homeostasis e.g. osteoporosis. Here, we review the current state of knowledge of the development, regulation and control of the human hair follicle pigmentary unit during life.

Aging↗

Phenotypical characteristics, lifestyle, social class and uveal melanoma.

PURPOSE: To investigate potential risk factors of uveal melanoma, including phenotypical characteristics, eye burns, social class, smoking and alcohol consumption. METHODS: A hospital-based and population-based case-control study of uveal melanoma was carried out from 1995 through 1998 and the results pooled. A total of 118 patients (59 men and 59 women) with uveal melanoma and 475 controls matching on sex, age and study regions were interviewed. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: There was an elevated risk for blue or grey iris color (OR = 3.0, 95% CI 1.5-6.0). Red or blond hair color at age 20 was slightly associated with an increased risk for uveal melanoma (OR = 1.5, 95% CI 0.9-2.4). There was no elevated risk for a history of eye burns (OR = 1.1, 95% CI 0.5-2.4). CONCLUSIONS: Among the potential risk factors studied, only the phenotypical characteristics showed an association with the risk of uveal melanoma.

Adult↗

Epidemiologic study of ocular/adnexal squamous cell carcinoma in horses.

Proportional hospital accession ratios for equine ocular/adnexal squamous cell carcinoma (SCC) were determined for 14 colleges of veterinary medicine participating in the Veterinary Medical Data Program between January 1978 and December 1986. Comparison of the ratios with their respective geographical, physical data has shown an increased prevalence of SCC with an increase in longitude, altitude, or mean annual solar radiation. In contrast, prevalence of SCC increased with a decrease in latitude. Between January 1978 and December 1988, 147 horses with ocular/adnexal SCC were admitted to the Colorado State University Veterinary Teaching Hospital. Diagnosis was confirmed by histologic examination of appropriate tissue specimens. Medical records provided information regarding month and year of admission and diagnosis, age at diagnosis, breed, gender, and hair color. Comparison with a randomly selected hospital control population revealed an increased prevalence of ocular/adnexal SCC with an increase in age (P less than 0.001). Compared with Quarter Horses, draft breeds (Belgian, Clydesdale, and Shire) and Appaloosas had a significantly (P less than 0.001) greater prevalence of ocular/adnexal SCC. Sexually intact males and females were significantly (P less than 0.001) less likely (5 and 2 times, respectively) to have ocular/adnexal SCC when compared with castrated males. The prevalence of ocular/adnexal SCC was significantly greater for all hair colors when compared with bay, brown, or black (P less than 0.01).

Age Factors↗

Mahogany/attractin: en route from phenotype to function.

The mouse mahogany mutation affects melanocortin signaling pathways that regulate energy homeostasis and hair color. The gene mutated in mahogany mice encodes attractin, a large transmembrane protein that is broadly expressed and conserved among multicellular animals. Mouse attractin is likely to have additional roles outside melanocortin signaling, and cloning of the gene provides information that can be used to form testable hypotheses about its biochemical function.

Animals↗

The Chediak-Higashi syndrome of cats.

Initial clinical, genetic, cytochemical and ultrastructural studies have characterized the Chediak-Higashi syndrome in cats. Three cats with Chediak-Higashi syndrome were found in a single line of 27 Persian cats, and three additional affected cats were produced from two prospective breedings of the original line. The disorder was characterized genetically as an autosomal recessive condition. All cats in the line with the combination of yellow eye color and "blue smoke" hair color exhibited the disorder. Four of the five cats examined had bilateral nuclear cataracts as early in life as 3 months of age. No increased susceptibility to infectious disease was observed. A bleeding tendency was noted. Abnormally large eosinophilic, sudanophilic, peroxidase-containing granules were observed in the neutrophils of the granulocytic series of blood and bone marrow by electron and light microscopy. Granules of eosinophils and basophils were also enlarged. Light microscopic studies of hair and skin revealed enlarged melanin granules. These manifestations were similar to those in man, mink, cattle, mice, and the killer whale with Chediak-Higashi syndrome. Cats are the sixth species in which this genetic disease has been reported.

Animals↗

Risk factors for squamous cell carcinoma of the skin in Saskatchewan, Canada.

Completed questionnaires regarding suspected risk factors for skin cancer were completed by 178 cases of SCC of the skin in Saskatchewan, Canada, and 284 age- sex- and location-matched controls. Significant risk factors identified using chi2 analyses were: farming, family history of skin cancer, light eye color, blond or red hair color, skin types I or II, obvious freckles in childhood, history of severe sunburn, and the use of the herbicide 2,4-Dichlorophenoxy acetic acid. The following relative risks were identified: (1) All cases of SCC of the skin and matched controls: agricultural occupation 1.49, history of severe sunburn 1.49. (2) All men with SCC of the skin and matched controls: history of severe sunburn 1.36 (3) All women with SCC of the skin and matched controls: agricultural occupation 1.83, and skin types I or II 1.48. No association was noted on our study between a history of psoriasis and development of SCC. Neither was an association between smoking and SCC found.

Carcinoma, Squamous Cell↗

Has the butcher on the bus dyed his hair? When color changes modulate ERP correlates of familiarity and recollection.

Recognition memory is usually thought of as comprising two distinct memory processes, namely familiarity and recollection. This distinction is reflected in specific event-related potential (ERP) components associated with both subprocesses. A mid-frontal attenuated negativity for correctly recognized old items relative to new ones around 400 ms has been typically linked to familiarity, whereas a parietally accentuated, more pronounced positivity for old items from 500 to 800 ms has been connected with recollection. Recently, this classification has been challenged by relating the mid-frontal old/new effect to conceptual priming mechanisms. Moreover, the perceptual sensitivity of both old/new effects is still under debate. The present study used a recognition memory task for visual objects and nonsense figures in order to investigate the functional significance of both ERP old/new effects. With respect to study presentation, all items were either presented in a perceptually identical or a color-modified version at test. Old nonsense figures, despite being meaningless, elicited a reliable mid-frontal old/new effect, thereby strongly suggesting a close relationship to familiarity processes rather than conceptual priming. Additionally, both the mid-frontal and the parietal old/new effect for real objects were graded with respect to the perceptual similarity between study and test. We argue that not only recollection, but also familiarity processes can provide information about perceptual atttributes, which is used in the course of recognition memory decisions.

Adult↗

Hair zinc concentrations not subject to seasonal variation in adults in New Zealand.

The analysis of recently grown hair for zinc provides a biomarker of recent zinc status. Seasonal variation of zinc in hair has been demonstrated in children. The aim of this study was to investigate whether on a month-by- month basis there is a seasonal variation in hair zinc concentration in an apparently well-nourished adult population in New Zealand. It was hypothesized that increased hours of daylight would be associated with an increase in zinc concentration in hair. Thirty-four subjects (20 F, 14 M) aged 18-54 yr had occipital hair sampled at monthly intervals between June and December. Food variety was assessed by questionnaire. After thorough washing of the hair followed by nitric acid digestion, zinc was determined by flame atomic absorption spectrometry (FAAS) with special attention to the inclusion of blanks, internal and international standards, and reduction of contamination in each sample run. Analyses between two laboratories confirmed that two FAAS instruments were giving the same reading. No seasonal variation in hair zinc concentration was found. Reported dietary variety, ethnicity, gender, and hair color were unrelated to hair zinc concentrations in this population. This study adds to evidence that will help define the role of hair zinc in determining recent zinc status.

Adult↗

Risk factors for ocular melanoma: Western Canada Melanoma Study.

Between April 1, 1979, and March 31, 1981, 90 individuals in the four western provinces of Canada were diagnosed as having ocular melanomas. Of 87 age-eligible cases (age 20-79 yr), 65 (75%) were interviewed along with age- and sex-matched controls chosen at random from the provincial populations. Individuals with blue eyes had a significantly greater crude risk of ocular melanoma than those with brown eyes [odds ratio (OR)=3.0, P=.04]. Subjects with red or blonde hair were at higher risk of having ocular melanoma than those with black or dark-brown hair (OR=7.7, P=.03). Indoor workers appeared to be at elevated risk for ocular melanoma even after controlling for eye and hair color (OR=3.5, P=.006).

Adult↗

In vitro binding studies of drugs to hair: influence of melanin and lipids on cocaine binding to Caucasoid and Africoid hair.

Although the mechanism(s) of drug deposition in hair are unknown, there is evidence that suggests that the amount and type of melanin present are major factors in determining how much drug enters hair after exposure. The role of other hair components, such as lipids, has received less attention. We used in vitro binding techniques to evaluate the binding of radiolabeled cocaine to different types of treated and untreated hair specimens. Divided male and female Caucasoid (black/brown and blond colored) and Africoid (black colored) hair specimens (N = 7) were exhaustively extracted to remove lipid components (lipid-extracted hair). Separate portions were bleached to denature or alter melanin content. Experiments with radiolabeled cocaine were performed on untreated, lipid-extracted, and bleached portions of hair from different groups. Cocaine binding was significantly higher (p < .01) to male Africoid hair compared with other groups. The amount of drug binding was similar among female Africoid and male and female, black/brown Caucasoid specimens. The lowest amount of binding was observed with blond, female Caucasoid specimens. Binding experiments also revealed that specific cocaine binding generally did not differ significantly between lipid-extracted hair and untreated hair, but bleaching of most hair specimens resulted in significant (p < .01) decreases in specific binding compared with untreated hair. In separate experiments with cocaine-treated hair specimens, digested samples were evaluated to determine if removal of the insoluble melanin fraction from soluble hair components provided a means of normalization of drug content and elimination of color bias. Removal of the insoluble melanin fraction was not effective in removal of significant amounts of cocaine, which indicated that the digestion process released bound cocaine into the digest solution. Overall, these experiments suggested that lipids in hair play a minor role in drug binding, whereas melanin functions as a major binding site for cocaine. Natural (ethnic) or artificial (bleaching) differences in melanin content may determine the extent of cocaine entrapment in hair after drug exposure. Further, digestion of hair samples and removal of insoluble melanin failed to be effective in removal of hair color bias.

Analysis of Variance↗

Melanocortin-1 receptor: loss of function mutations and skin cancer.

We present a red-haired patient who came to our clinic seeking information regarding his predisposition to skin cancer. We discuss the receptor involved in hair color and the allelic variants that lead to red hair. These variants are often characterized by loss of function mutations, which lead to a predisposition to non-melanoma skin cancers, with relative risks reaching as high as a 6.7 in one study. Most concerning, however, is that some of these loss of function mutations may act synergistically with genetic mutations that cause familial melanomas. Thus, red haired patients with familial melanoma syndromes have a greater risk of melanoma than those patients with familial melanoma syndromes alone.

Adult↗

Red hair--a desirable mutation?

Red hair is one of the most striking variants of human hair coloration and has historically been of profound social importance. Red hair in man is due to certain loss of function mutations of one of the peptide products of the pro-opiomelanocortin (POMC) gene, the melanocortin-1 receptor (MC1R, MIM 155555). Such functional mutations enable the melanocyte to produce red-yellow pheomelanin in preference to the default, black-brown eumelanin. This paper reviews the path of discovery of the MC1R in control of animal coat colour, the subsequent role of MC1R in human physiology and possibly wider role of MC1R in human skin carcinogenesis and human development through history.

Animals↗

A MERRF/PEO overlap syndrome associated with the mitochondrial DNA 3243 mutation.

We describe a two-generation family with combined clinical features of myoclonic epilepsy, progressive external ophthalmoplegia (PEO), proximal myopathy, pigmentary retinopathy, progressive deafness, basal ganglia calcification, and ragged-red fibers in a muscle biopsy specimen. One family member died unexpectedly at age 22 years. The molecular tests revealed an A-to-G transition at nucleotide position 3243 of the mitochondrial tRNA(Leu(UUR)) gene. No one in this family had stroke-like episodes. Although the propositus (a 28-year-old woman) had a significant number of white hairs, the percentage of mutant mtDNA in white-hair roots was not different from that in the colored-hair roots. Our findings suggest that the 3243 mutation can be associated with mixed clinical features of myoclonic epilepsy with ragged-red fibers (MERRF) and PEO and that a preferential increase in the levels of the mutant mtDNA is not related to graying of hair, and hence to the hypothesized production of premature aging of cells.

Adult↗

Polyester but not cotton or wool textiles inhibit hair growth.

The effect of different types of textile fabrics on hair growth was investigated in 40 mongrel dogs divided into 5 groups. An area of 10 x 20 cm on the dog's back was shaved; half of this area was covered by a textile patch of 100% polyester material in the 1st group, 100% cotton in the 2nd group, 100% wool in the 3rd group and a 50%/50% polyester/cotton blend in the 4th group. The remaining half of the shaved area in the 4 groups as well as the whole area in the 5th group (control) were left uncovered. The textile patch was worn for 2 months. The polyester-covered hair grew at a significantly lower rate and density than in the uncovered area of the same animal and the controls (p < 0.01). The hair color was similar to that of the surrounding uncovered hair. This is in contrast to cotton- and wool-covered skin area which showed nonsignificant differences in hair density, growth rate and color (p > 0.05) against the uncovered area and controls. In the polyester-covered skin, a thinning of the epidermis of the skin was noted microscopically with fragmentation and vacuolation of the hair follicle pulp. The study has shown that the polyester material generated electrostatic potentials, which may have inhibited hair growth, whereas cotton and woolen textiles did not. Friction between the polyester textile and the skin generates electrostatic charges which are suggested to create an 'electrostatic field' that seems to be responsible for the inhibited hair growth.

Animals↗