Biomedical subjects

Tamar E C Nijsten

Publications and source records attributed to Tamar E C Nijsten.

4 recordsLinked to original sources

PubMed2025

Genome-wide association meta-regression identifies stem cell lineage orchestration as a key driver of acne risk.

Over 85% of the population experience acne at some point in their lives, with its severity spanning a quantitative spectrum, from mild, transient outbreaks to more persistent, severe forms of the condition. Moderate to severe disease poses a substantial global burden arising from both the physical and psychological impacts of this highly visible condition. The analytical approach taken in this study aimed to address the impact of variation in the dichotomisation of acne case control status, driven by ascertainment and study design, on effect size estimates across independent genetic association studies of acne. Through a fixed intercept meta-regression framework, we combined evidence genome-wide for association with acne across studies in which case-control status had been ascertained in different settings, allowing for different severity threshold definitions. Across a combined sample of 73,997 cases and 1,103,940 controls of European, South Asian and African American ancestry we identify genetic variation at 165 genomic loci that influence acne risk. There is evidence for both shared and ancestry specific components to the genetic susceptibility to acne and for sex differences in the magnitude of effect of risk alleles at three loci. We observe that common genetic variation explains 13.4% of acne heritability on the liability scale. Consistent with the hypothesis that genetic risk primarily operates at the level of individual pilosebaceous units, a polygenic score derived from this case-control study of acne susceptibility is associated with both self-reported and clinically assessed acne severity in adolescence, further strengthening the link between genetic risk and disease severity. Prioritisation of causal genes at the identified acne risk loci, provides genetic validation of the targets of established and emerging acne therapies, including retinoid treatments. The identified acne risk loci are enriched for genes encoding downstream effectors of RXRA signalling, including SOX9 and components of the WNT and p53 pathways. Illustrating that the control of stem cell lineage plasticity and cellular fate are important mechanisms through which genetic variation influences acne susceptibility within the pilosebaceous unit.

Journal Article↗

PubMed2006

Testing and reducing skindex-29 using Rasch analysis: Skindex-17.

The Skindex is a well-studied dermatology-specific health-related quality of life (HRQOL) instrument. The objective of this study was to test Skindex-29 using Rasch analysis and, if necessary, to refine it so that it would fit this item response theory based model. The Skindex-29 of 454 Italian dermatological patients was subjected to Rasch analysis to investigate threshold order, differential item functioning (DIF), and item and overall fit to the model. The Skindex-29 did not fit the Rasch model (P<0.001). The 5-point scoring system was re-grouped into three categories and demonstrated logical response order for all but one item. Rasch analyses of a combined emotion and social functioning subscale of Skindex-29 resulted in a 12-item psychosocial subscale. Five of seven items were retained in a symptoms subscale. Both subscales fitted the model (P=0.32 and 0.13, respectively) without significant individual item misfit or DIF (P>0.05). Classical psychometric properties such as response distribution, item-rest correlation, item complexity, and internal consistency of the two subscales of Skindex-17 were at least adequate. The Skindex-17 is a Rasch reduced version of Skindex-29, with two independent scores that can be used in the measurement of HRQOL in dermatological patients.

Adult↗

PubMed2003

The increased risk of skin cancer is persistent after discontinuation of psoralen+ultraviolet A: a cohort study.

Psoralen+ultraviolet A-treated psoriasis patients are at increased risk for nonmelanoma skin cancer. To assess the persistence of cancer risk among patients who have discontinued psoralen+ultraviolet A and the risk of a first tumor with the passage of time, we prospectively studied the incidence in a cohort of 1,380 psoriasis patients treated with psoralen+ultraviolet A. We observed a total of 27,840 person-years of which 59.4% were considered years without psoralen+ultraviolet. No significant decrease in risk was noted during the first 15 years after psoralen+ultraviolet A was discontinued. Subsequently, the risk of squamous cell carcinoma was reduced (incidence rate ratio=0.79; 95%CI=0.62, 1.01 on treatment vs >15 years off). After 25 years, about 7% of patients with < or =200 psoralen+ultraviolet A treatments and more than half of the patients with > or =400 treatments develop at least one squamous cell carcinoma. After 25 years, almost one third of the patients exposed to > or =200 treatments developed at least one basal cell carcinoma. In conclusion, substantial exposure to psoralen+ultraviolet A dramatically increases the risk of nonmelanoma skin cancer and prior exposure to psoralen+ultraviolet A remains an important issue in the management of patients because the cancer risk associated with psoralen+ultraviolet A is persistent.

Basal Cell Carcinoma↗

PubMed2003

Oral retinoid use reduces cutaneous squamous cell carcinoma risk in patients with psoriasis treated with psoralen-UVA: a nested cohort study.

BACKGROUND: Small open studies of patients at high risk for squamous cell carcinoma (SCC) of the skin suggest that oral retinoid use reduces the risk of these tumors. Among patients at lower risk, randomized trials of low doses of retinoids did not demonstrate significant chemopreventive effects. Patients with psoriasis treated with oral psoralen-UVA have a high risk of SCC development. Oral retinoids are used to treat psoriasis. We performed a nested cohort study to assess whether oral retinoids reduce skin cancer risk among patients with psoriasis exposed to psoralen-UVA. METHODS: From 1985 to 2000, 135 patients (11.3% of surviving patients in our cohort) used retinoids for at least 26 weeks in 1 year or more. For these 135 patients, we compared each person's SCC and basal cell carcinoma incidence during years of substantial oral retinoid use and other years. We used Poisson regression models to adjust for potential confounders. RESULTS: In a paired analysis, which compared each patient's own tumor experience while using and not using retinoids, retinoid use was associated with a 30% reduction in SCC incidence (196 SCCs/1000 and 302 SCCs/1000 years of use and no use, respectively; P =.002). After adjusting for other factors associated with SCC risk, the incidence of SCC was significantly decreased during years of substantial retinoid use (incidence rate ratio = 0.79; 95% confidence interval = 0.65, 0.95). Oral retinoid use and basal cell carcinoma incidence were not significantly associated. CONCLUSION: In patients with psoriasis treated with psoralen-UVA, systemic retinoid use reduced SCC risk but did not significantly alter basal cell carcinoma incidence.

Adult↗