Alcohol or tobacco use does not further increase risk of HPV16-associated pharyngeal cancer. HNSCC risk associated with smoking, alcohol, and HPV16 differs by tumor site.

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.

Background Left truncation occurs when subjects who otherwise meet entry criteria do not remain observable for a later start of follow-up. We investigated left truncation in occupational studies due to inclusion of workers hired before the start of follow-up in a simulation study. Methods Using Monte Carlo methods, we simulated null and positive associations between exposure (work duration) and mortality for 500 datasets of 5000 subjects, assuming the absence and presence of heterogeneity in susceptibility to disease and to the effect of exposure. We examined incident hires (followed since hire) and left-truncated prevalent hires (those hired before baseline and remained employed at baseline). We estimated the association ( β^1∗) as the mean slope using Cox proportional hazards with a linear term for exposure, under scenarios with and without susceptibility. Results With homogeneous susceptibility, there were no differences between incident and prevalent hires. Introducing only disease susceptibility did not change results. However, with heterogeneous susceptibility to the effect of exposure, downward bias was observed among prevalent hires under both the true null and positive exposure-response scenarios. The bias increased with time between hire and baseline (null: β^1∗=0.050.16667emfalse[SD=0.08false],0.16667emβ^1∗=-0.080.16667emfalse[SD=0.24false],0.16667emβ^1∗=-0.180.16667emfalse[SD=0.98false] if hired <15, 15 to <30, and ≥30 years before baseline, respectively), coincident with a decreasing percentage of susceptible subjects. Conclusions: Prevalent hires induce downward bias in an occupational cohort. This occurs because subjects who are less susceptible to the exposure remain exposed the longest, thereby underestimating the association.

Despite loss in power and restricted exposure range, decreasing the relative proportion of prevalent to incident hires reduced HWSE bias, resulting in stronger evidence for a dose-response between silica exposure and lung cancer mortality.

The genotoxic effects of ultraviolet (UV) radiation are well-known causes of skin cancers; however, UV radiation also suppresses the immune system, decreasing the body's surveillance for tumor cells. In experimental systems, UV radiation immunosuppression is at least partially mediated through urocanic acid (UCA), an UV radiation-absorbing molecule in the stratum corneum. We tested the hypothesis that genetic variation in the histidase gene (HAL), which catalyzes the formation of UCA in the skin, modifies risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in a population-based study (914 BCC, 702 SCC and 848 controls). We observed no evidence of a main gene effect for the HAL I439V polymorphism (rs7297245) and BCC or SCC. However, we found a HAL genotype-sunburn interaction in association with BCC (P for interaction 5 0.040) and SCC (P for interaction 5 0.018). A HAL genotype-SCC association was observed primarily among women (odds ratio 5 1.5, 95% confidence interval 1.1-2.2), and among women, we found an interaction between HAL genotype and oral contraceptive use on SCC risk (P 5 0.040). The variant HAL allele likewise appeared to modify the SCC risk associated with glucocorticoid steroid usage (P for interaction 5 0.0004). In conclusion, our findings are a first step in determining the genetic underpinnings of UV immune suppression and have identified important new genetic interactions contributing to the etiology of skin cancer.

Overall, caregivers had lower mortality rates than noncaregivers in all analyses. These associations were sensitive to the lagged period, indicating that the timing of leaving caregiving does influence this relationship and should be considered in future investigations.

Background Diagnosed diabetes mellitus (DM) is a consistently documented risk factor for ischemic stroke in patients with atrial fibrillation (AF). Objectives To assess the association between duration of diabetes and elevated HbA1c with risk of stroke among diabetics with AF. Methods We assessed this association in the ATRIA California community-based cohort of AF patients (study years 1996-2003) where all events were clinician adjudicated. We used Cox proportional hazards regression to estimate the rate of ischemic stroke in diabetic patients according to time-varying measures of estimated duration of diabetes (≥3 years compared to <3 years) and HbA1c values (≥9.0% and 7.0-8.9% compared to <7.0%), focusing on periods where patients were not anticoagulated. Results There were 2,101 diabetic patients included in the duration analysis, 40% with duration <3 years and 60% with duration ≥3 years at baseline. Among 1933 diabetic patients included in the HbA1c analysis, 46% had HbA1c <7.0%, 36% between 7.0 and 8.9%, and 19% ≥9.0% at baseline. Duration of diabetes ≥ 3 years was associated with an increased rate of ischemic stroke compared to duration <3 years (adjusted HR: 1.74, 95% CI: 1.10-2.76). The increased stroke rate was observed in older (≥75 years) and younger (<75 years) individuals. Neither poor glycemic control (HbA1c ≥9.0%, adjusted HR: 1.04, 95% CI: 0.57-1.92) or moderately increased HbA1c (7.0-8.9%, adjusted HR: 1.21, 95% CI: 0.77-1.91) were significantly associated with an increased rate of ischemic stroke compared with patients who had HbA1c <7.0%. Conclusions Duration of diabetes is a more important predictor of ischemic stroke than glycemic control in patients who have diabetes and AF.

Although skin tumors are highly immunogenic, exposure to UV radiation is known to suppress immune responses via regulatory T cells. Specifically, the activity of cytotoxic lymphocyte-associated antigen-4 (CTLA-4) is integral in regulating the development of UV-induced tolerance and, concomitantly, skin cancers. Due to the inverse relationship between tumor surveillance and autoimmunity, we hypothesize that the same genetic variant in the CTLA4 locus that increases risk for autoimmune diseases is associated with decreased risk of non-melanoma skin cancer (NMSC). We analyzed whether the polymorphism CT60 or haplotypes of CTLA4 influence odds of developing the major types of NMSC, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), in a population-based case-control study of Caucasians in New Hampshire (849 controls, 930 BCC, and 713 SCC). The CTLA4 CT60 GG genotype was associated with decreased odds for BCC and SCC, controlling for age, sex, lifetime number of severe sunburns, and skin type [BCC: odds ratio (OR), 0.7; 95% confidence interval (95% CI), 0.5-0.9; SCC: OR, 0.7; 95% CI, 0.5-1.0]. For BCC, this decrease was apparent largely among those with a higher lifetime number of severe sunburns (P interaction = 0.0074). There were significantly decreased odds of disease associated with two haplotypes, which possess the CT60 G allele. Additionally, lifetime number of severe sunburns modestly altered the effects of the CTLA4 haplotypes in BCC, and the association seemed driven by the CT60 single nucleotide polymorphism. In conclusion, genetic variation at the CTLA4 locus may be etiologically important in NMSC, the most prevalent malignancy in the United States.