Our findings support a role for HPV types from the genus beta in the pathogenesis of SCC.

Recent studies in northeastern Pennsylvania report higher concentrations of dissolved methane in domestic water wells associated with proximity to nearby gas-producing wells [ Osborn et al. Proc. Natl. Acad. Sci. U. S. A. 2011 , 108 , 8172 ] and [ Jackson et al. Proc. Natl. Acad. Sci. U. S. A. , 2013 , 110 , 11250 ]. We test this possible association by using Chesapeake Energy's baseline data set of over 11,300 dissolved methane analyses from domestic water wells, densely arrayed in Bradford and nearby counties (Pennsylvania), and near 661 pre-existing oil and gas wells. The majority of these, 92%, were unconventional wells, drilled with horizontal legs and hydraulically fractured. Our data set is hundreds of times larger than data sets used in prior studies. In contrast to prior findings, we found no statistically significant relationship between dissolved methane concentrations in groundwater from domestic water wells and proximity to pre-existing oil or gas wells. Previous analyses used small sample sets compared to the population of domestic wells available, which may explain the difference in prior findings compared to ours.

It is well-known that ultraviolet (UV) light exposure and a sun sensitive phenotype are risk factors for the development of non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In this New Hampshire population-based case-control study, we collected data from 5,072 individuals, including histologically-confirmed cases of BCC and SCC, and controls via a personal interview to investigate possible associations between photosensitizing medication use and NMSC. After adjustment for potentially confounding factors (e.g. lifetime number of painful sunburns), we found a modest increase in risk of SCC (OR = 1.2, 95% CI = 1.0–1.4) and BCC (OR = 1.2, 95% CI = 0.9–1.5), in particular early-onset BCC, (≤ 50 years of age) (OR = 1.5, 95% CI = 1.1–2.1) associated with photosensitizing medication use. For SCC the association was strongest amongst those with tendency to sunburn rather than tan. We also specifically found associations with BCC, and especially early-onset BCC, and photosensitizing antimicrobials. In conclusion, certain commonly prescribed photosensitizing medications may enhance the risk of developing SCC, especially in individuals with a sun sensitive phenotype, and may increase the risk of developing BCC and incidence of BCC at a younger age.

Objective To investigate the association between genus β human papillomaviruses and the incidence of nonmelanocytic skin cancer in the general population. Design Population based case-control study. Setting New Hampshire, USA. Participants 2366 skin cancer cases and controls from the general population aged 25 to 74 years (663 squamous cell carcinoma, 898 basal cell carcinoma, 805 controls), with plasma samples tested for L1 antibodies to 16 genus β human papillomaviruses by multiplex serology. Main outcome measures Odds ratios for squamous cell carcinoma and basal cell carcinoma associated with seropositivity to β human papillomaviruses. Results Squamous cell carcinoma, but not basal cell carcinoma, cases had a higher prevalence of each of the individual β human papillomaviruses assayed compared with controls. The odds ratios for squamous cell carcinoma increased with the number of β types positive (odds ratio for one type positive 0.99 (95% confidence interval 0.74 to 1.33); two to three types positive 1.44 (1.03 to 2.01); four to eight types positive 1.51 (1.03 to 2.20); more than eight types positive 1.71 (1.12 to 2.62); P for trend (categorical)<0.001; P for trend (continuous) =0.003). With limited statistical power, the association was stronger among long term users of systemic glucocorticoids (odds ratio 3.21, 1.22 to 8.44) than among non-users (1.23, 0.97 to 1.55). Conclusions These findings support a relation between genus β human papillomavirus infection and the incidence of squamous cell carcinoma of the skin in the general population, as well as potential enhancement of risk by immunosuppression.

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States.Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population.Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses.Results: In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC.Conclusions: These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association.Citation: Gilbert-Diamond D, Li Z, Perry AE, Spencer SK, Gandolfi AJ, Karagas MR. 2013. A population-based case–control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA. Environ Health Perspect 121:1154–1160; http://dx.doi.org/10.1289/ehp.1206178

Ultraviolet radiation exposure is the dominant environmental determinant of all major forms of skin cancer; however, the nature of the association is incompletely understood. Existing instruments to capture sun exposure history tend to yield reproducible results, but the validity of these responses is unknown. To address this question, the authors examined the relation between responses to a standardized sun exposure instrument and histologic evidence of actinic damage in a population-based study of keratinocyte cancers from New Hampshire diagnosed from July 1, 1997, through March 31, 2000. A single study dermatopathologist histologically reviewed the adjacent skin of 925 skin cancer biopsies for the presence of solar keratoses and the extent of solar elastosis. The authors compared these measures with responses to a personal interview on history of sunburns, sunbathing, and time spent outdoors. Focusing on site-specific exposure, they found variables that estimated cumulative exposure related to histologic evidence of actinic damage. In contrast, measures of acute/intermittent exposure were generally unrelated to solar damage histologically. Findings suggest that cumulative, but not intermittent, measures of sun exposure derived from a personal interview appear to reflect a person's exposure history based on histologic evidence.

An increasing number of studies report that genus beta human papillomaviruses (HPVs) are associated with skin cancer, with suggestions of specificity for squamous cell carcinoma (SCC) of the skin. We have conducted a systematic examination of HPV DNA in tumors from immunocompetent hosts, including SCC and basal cell carcinoma (BCC), using a highly sensitive methodology and population-based samples to test the hypothesis that a differential prevalence of beta-HPVs exists between SCC (n=101) and BCC (n=101) tumors. When testing for all known beta-HPV types, we found no significant difference in HPV prevalence between the two histologies. However, SCC lesions were significantly more likely to be infected with HPV genus beta-species 1 (includes types 5 and 8), than BCC samples (P=0.01); this difference was not observed for any other species. A histologic difference was also observed for those HPV types previously reported to be important in skin cancer (P=0.003). SCC samples showed a higher rate of infectivity (that is, were positive for multiple types) than BCC tumors (P=0.02). These data highlight the potential importance of various genus beta-HPV types, in particular genus beta-species 1 in SCC, and support the hypothesis of a behavioral difference of the virus within the two major histological skin cancers.

Although benign and atypical moles are considered key melanoma risk factors, previous studies of their influence were small and/or institution-based. We conducted a population-based case-control study in the state of New Hampshire. Individuals of ages 20-69 with an incident diagnosis of first primary cutaneous melanoma were ascertained through the New Hampshire State Cancer Registry. Controls were identified through New Hampshire driver's license lists and frequency-matched by age and gender to cases. We interviewed 423 eligible cases and 678 eligible controls. Host characteristics, including mole counts, were evaluated using logistic regression analyses. Our results showed that pigmentary factors, including eye color (OR = 1.57 for blue eyes compared to brown), hair color (OR = 1.85 for blonde/red hair color compared to brown/black), freckles before age 15 (OR = 2.39 for freckles present compared to absent) and sun sensitivity (OR = 2.25 for peeling sunburn followed by no tan or a light tan and 2.42 for sunburn followed by tan compared to tanning immediately), were related to melanoma risk; these associations held after adjustment for sun-related factors and for moles. In analyses confined to skin examination participants, the covariate-adjusted effects of benign and atypical moles were moderately strong. Compared to 0-4 benign moles, risk increased steadily for 5-14 moles (OR = 1.71), 15-24 moles (OR = 3.55) and 25 moles (OR = 4.33). Risk also increased with the number of atypical moles; compared to none, the ORs for having 1, 2-3, or 4 atypical moles were 2.08, 1.84 and 3.80, respectively. Although risk was highest for those with multiple benign and atypical moles, the interaction was not of statistical significance. Our findings, arising from the first population-and incidence-based study to evaluate atypical moles in relation to melanoma risk, confirm the importance of host susceptibility, represented by pigmentary factors and the tendency to develop benign or atypical moles, in the etiology of this disease. ' 2005 Wiley-Liss, Inc.Key words: melanoma; moles; atypical moles; pigmentary characteristics; sun sensitivity Numerous epidemiologic studies of melanoma risk have shown a modest to moderate influence of pigmentary factors.1-4 Associations with sunburn or sun exposure are also widely reported, 3,[5][6][7] although findings are inconsistent.8 Over the last 2 decades, in response to clinical reports of multiple benign and atypical moles occurring in nonfamilial melanoma patients, 9 epidemiologic studies have sought to quantify the relationship between these lesions and melanoma risk. Research results have demonstrated strong associations between melanoma risk and benign mole counts, whether self-counted 1 or assessed by examiners. 3,10-20 Although several studies have also shown strong associations between atypical moles, the putative melanoma precursors and melanoma risk, these efforts were wholly or in part institution-based and/or involved small numbers of cases. [11][12][13][14][15][16][19][20][21][22...