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1.
J Prof Nurs ; 37(3): 516-520, 2021.
Article in English | MEDLINE | ID: mdl-34016308

ABSTRACT

With the rapid proliferation of Doctor of Nursing Practice (DNP) programs, academic-practice partnerships are critical in the implementation of rigorous and valuable scholarly projects. However, the failure to develop meaningful partnerships can have unintended consequences, particularly when students and practice sites do not have the preparation and support to navigate these partnerships. Four case studies are presented that explore the issues of preserving autonomy, practicing stewardship, imposing unfair burden and maintaining project fidelity. Best practices are presented to promote equitable collaboration and a mutually beneficial experience. Universities must have the resources required to generate expert clinicians able to translate research into practice and support effective academic-practice partnerships.


Subject(s)
Education, Nursing, Graduate , Students, Nursing , Curriculum , Humans , Universities
3.
JAMA Dermatol ; 155(2): 188-195, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30566178

ABSTRACT

Importance: Information on risk factors of subsequent melanomas would be helpful to identify patients at risk after the diagnosis of their first melanomas. Objective: To determine risk factors of subsequent melanomas. Design, Setting, and Participants: In this retrospective case-control study, 1648 participants with histologically verified cutaneous melanoma diagnosed from January 1, 1968, though March 16, 2015, were recruited from a tertiary referral center as part of the Molecular Markers of Melanoma study. CDKN2A was sequenced in 514 and MC1R in 953 participants. Data were analyzed from March 7, 2008, through March 25, 2015. Main Outcomes and Measures: Phenotypic traits and internal and external risk factors for the development of a second, third, or fourth melanoma. Results: In total, 1648 patients (53.6% men; mean [SD] age, 54 [15] years) were enrolled, including 1349 with single and 299 with multiple primary melanoma. Mean (SD) age at recruitment was 57 (15) years for the single-melanoma and 62 (14) years for the multiple-melanoma groups. From the internal risk factors, family history (odds ratio [OR], 1.76; 95% CI, 1.22-2.55; P = .006), CDKN2A high-risk mutations (OR, 4.03; 95% CI, 1.28-12.70; P = .02), and high numbers of nevi as a phenotypic risk factor (ORs, 2.23 [95% CI, 1.56-3.28, P < .001] for 20-30 smaller nevi and 2.56 [95% CI, 1.50-4.36; P = .003] for 20-30 larger nevi) were significantly associated with the risk of developing a subsequent primary melanoma using multivariate logistic regression analysis. Nonmelanoma skin cancer (OR, 2.57; 95% CI, 1.84-3.58; P < .001) and signs of actinic skin damage, particularly on the back (ORs, 1.91 [95% CI, 1.12-3.25; P = .04] for freckling and 1.92 [95% CI, 1.29-3.08; P = .007] for solar lentigines), additionally increased risk of a subsequent melanoma. All those factors were also associated with an earlier development of the second melanoma. Patients with 3 melanomas developed their second melanoma earlier than patients with only 2 melanomas (mean [SD] age, 55 [15] years for those with 2 primary melanomas; 52 [15] years for those with 3 primary melanomas). Time spent outdoors, solarium use, outdoor occupation, and hair color had no significant associations in these models. Conclusions and Relevance: According to the results of this study, internal factors (family history and genetic variants), number of nevi, and actinic damage on the back are more relevant for the development of subsequent melanomas than skin phototype or hair color. Patients with many nevi were younger at the time of the diagnosis of their first melanoma. This finding could help to identify persons at increased risk of developing multiple primary melanomas.


Subject(s)
Genetic Predisposition to Disease/epidemiology , Melanoma/epidemiology , Melanoma/genetics , Neoplasm Recurrence, Local/epidemiology , Skin Neoplasms/epidemiology , Skin Neoplasms/genetics , Age Distribution , Analysis of Variance , Austria , Case-Control Studies , Female , Humans , Logistic Models , Male , Melanoma/pathology , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prevalence , Retrospective Studies , Risk Factors , Sex Distribution , Skin Neoplasms/pathology , Survival Analysis , Melanoma, Cutaneous Malignant
4.
Nurs Educ Perspect ; 40(2): 107-109, 2019.
Article in English | MEDLINE | ID: mdl-29957652

ABSTRACT

Clinical nurses' perceptions of a senior capstone dedicated educational unit (DEU) model to transition to practice was evaluated in a pilot study. Nursing students were placed in the traditional capstone and the DEU senior capstone unit with clinical nurses. Staff nurses completed an online survey to compare and contrast satisfaction and effectiveness of the models. The results of the study revealed no perceived differences in the outcomes of a DEU experience as compared to the traditional preceptor model. However, nursing management reported an improved sense of leadership and teamwork on the unit with the DEU model.


Subject(s)
Education, Nursing, Baccalaureate , Students, Nursing , Humans , Models, Educational , Pilot Projects
5.
J Nurs Educ ; 57(10): 620-623, 2018 Oct 01.
Article in English | MEDLINE | ID: mdl-30277548

ABSTRACT

BACKGROUND: The Northeast Region VA Nursing Alliance is an academic-practice partnership founded in 2007 between the Veteran's Administration (VA) Boston/Bedford HealthCare Systems and six schools of nursing. METHOD: The purpose of this retrospective review was to examine the outcomes of the Northeast Region VA Nursing Alliance in accordance with the mission, goals, and sustainability of the alliance. RESULTS: The review confirmed that the alliance has successfully accomplished the mission and goals and continues to be a leader in academic-practice partnerships. CONCLUSION: Since inception, the academic-practice partnership has increased the number of clinical rotations and clinical faculty, educated nursing students on the care of Veterans, developed dedicated educational nursing units, increased Veteran-centered research, and provided a plethora of educational programs to increase knowledge related to Veteran health care issues. [J Nurs Educ. 2018;57(10):620-623.].


Subject(s)
Cooperative Behavior , Education, Nursing/organization & administration , Hospitals, Veterans/organization & administration , Interprofessional Relations , Patient Care Team/organization & administration , Veterans , Humans , Students, Nursing , United States , United States Department of Veterans Affairs
6.
JAMA Dermatol ; 154(7): 789-795, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29898205

ABSTRACT

Importance: Recently, the red hair variants of MC1R were found to contribute differently to pigmentation phenotype in males and females. Objective: To investigate the role of these variants in melanoma risk in males and females separately because carriers of the red hair variants of MC1R are at increased risk of melanoma. Design, Setting, and Participants: In this hospital-based, case-control study, we evaluated the effect of MC1R and melanoma risk for males and females separately by performing multivariate logistic regression analyses. Main Outcomes and Measures: Association of MC1R variants and melanoma risk in males and females. Results: A total of 905 females (473 melanoma cases, 432 controls) and 886 males (518 melanoma cases, 368 controls) were included in the analyses. The mean (SD) age of the study population was 59.2 (15.6). In females, carrying any MC1R red hair variants remained an independent risk factor of melanoma in a multivariable analysis (adjusted odds ratio [OR], 2.19 [95% CI, 1.60-2.99]), whereas in males, only signs of actinic skin damage (lentigines on the back [OR, 2.56; 95% CI, 1.47-4.45; P = .001] and the hands [OR, 2.31; 95% CI, 1.24-4.29; P = .008] and wrinkling on the neck [OR, 2.17; 95% CI, 1.23-3.82; P = .007]) and sunburns (OR, 1.65; 95% CI, 1.12-2.42; P = .01) remained significant risk factors. Conclusions and Relevance: MC1R variants contribute differently to melanoma risk in males and females. This could be helpful to better classify melanoma risk factors between the sexes.


Subject(s)
Melanoma/epidemiology , Melanoma/genetics , Receptor, Melanocortin, Type 1/genetics , Skin Neoplasms/epidemiology , Skin Neoplasms/genetics , Adult , Aged , Austria/epidemiology , Case-Control Studies , Female , Genetic Variation , Hair Color/genetics , Humans , Lentigo/epidemiology , Male , Middle Aged , Neck , Phenotype , Risk Factors , Sex Factors , Skin Aging , Skin Pigmentation/genetics , Sunburn/epidemiology
7.
G3 (Bethesda) ; 8(5): 1475-1480, 2018 05 04.
Article in English | MEDLINE | ID: mdl-29523635

ABSTRACT

Risk of melanoma is in part determined by genetic factors. Currently the only established high penetrance familial melanoma genes are CDKN2A and CDK4. Recent studies reported germline variants in POT1 in melanoma families. In the present study, we sequenced the entire POT1 gene in 694 patients from the M3-study. Patients with multiple primary melanomas (n = 163) or with a positive family history (n = 133) were classified as high-risk melanoma patients. Additionally, 200 single primary melanoma patients and 198 non-melanoma controls were sequenced. For prediction analysis 10 different tools were used.In total 53 different variants were found, of which 8 were detected in high-risk melanoma patients, only. Two out of these 8 variants were located in exons and were non-synonymous: g.124510982 G>A (p.R80C) and g.124491977 T>G (p.N300H). While g.124491977 T>G was predicted to be neutral, 80% of the prediction tools classified g.124510982 G>A as deleterious. The variant, g.124467236 T>C, which possibly causes a change in the splice site was identified in a case with a positive family history in the present study. Another variant in the 5-UTR, g.124537261 A>G, was found in 2 high-risk patients. So, in conclusion, melanoma associated POT1 germline variants seem to be rare. Further studies are required to evaluate the role of POT1 for genetic counseling.


Subject(s)
Genetic Predisposition to Disease , Germ-Line Mutation/genetics , Melanoma/genetics , Telomere-Binding Proteins/genetics , Aged , Austria , Cyclin-Dependent Kinase Inhibitor p16 , Cyclin-Dependent Kinase Inhibitor p18/genetics , Female , Humans , Male , Middle Aged , Risk Factors , Shelterin Complex
8.
Nurse Educ ; 43(6): 322-325, 2018.
Article in English | MEDLINE | ID: mdl-29438194

ABSTRACT

Determining the best ways to teach military culture and the veteran experience to nursing students and new nurses is an essential component in developing a culturally sensitive nursing workforce. The purpose of this article is to describe a theory-driven, experiential learning approach to integrating the Veterans History Project into the curricula for a postbaccalaureate nurse residency program. Participants acknowledged that this educational project better prepared them to care for the veteran population.


Subject(s)
Education, Nursing, Graduate/organization & administration , Patient-Centered Care , Students, Nursing/psychology , Teaching , Veterans Health/education , Curriculum , Humans , Nursing Education Research , Nursing Evaluation Research , Nursing Methodology Research
9.
MedEdPORTAL ; 14: 10766, 2018 10 19.
Article in English | MEDLINE | ID: mdl-30800966

ABSTRACT

Introduction: Health care is increasingly being provided by interprofessional teams. Academic medical centers (AMCs) need to offer educational experiences for trainees to work on these teams. Few resources exist to guide educational leaders in developing and implementing these experiences to meet the unique needs of their AMC. A commonly used planning tool is the strengths, weaknesses, opportunities, and threats (SWOT) analysis, which can help organizations identify issues and develop strategies that overcome barriers to program implementation. Methods: This workshop focuses on teaching participants to use a SWOT analysis to develop interprofessional learning activities. The workshop contains both a didactic component and an experiential component. The workshop was offered as a 60-minute webinar and a 120-minute in-person presentation. The additional hour during the in-person presentation was used for experiential learning activities. Eighty-four educators from a number of health professions attended the webinar, and approximately 50 medical educators attended the in-person presentation. Results: Participants reported satisfaction with the workshop and found its content met stated learning objectives. Participants believed they gained both the knowledge to develop a strategic plan to implement interprofessional educational programming and the ability to apply this knowledge at their AMC. Participants reported that their confidence in using strategic planning increased due to workshop participation. Discussion: This workshop represents a first step in helping educational leaders learn and use strategies to develop and implement interprofessional educational programming unique to their AMC. This programming is important for training future health care providers to work on interprofessional health care teams.


Subject(s)
Health Personnel/education , Academic Medical Centers/methods , Academic Medical Centers/organization & administration , Adult , Education/methods , Female , Health Personnel/trends , Humans , Interprofessional Relations , Male , Middle Aged , Surveys and Questionnaires
10.
J Prof Nurs ; 33(2): 108-112, 2017.
Article in English | MEDLINE | ID: mdl-28363384

ABSTRACT

Over the past decade, health care leaders have called for a radical transformation in health care and nursing education. Patient care has become complex, demanding succinct interprofessional communication and collaboration to optimize the care of the patient, and the nurse at the bedside is the optimal leader at the point of care. Assistance with the clinical reasoning and critical thinking with nursing students is pivotal for successful patient outcomes. The expert clinical nurse at the bedside is the premier faculty to guide the young practitioner in the care of the patient. A dedicated educational unit (DEU) is an example of an academic-practice partnership designed to provide students with a positive clinical learning environment. The purpose of this qualitative research study was to identify the role perceptions of staff nurse's participating as clinical instructors on a DEU and the perceived educational learning needs of the experienced staff nurses. After Veterans Affairs Boston Healthcare System Institutional Review Board approval, a total of 8 nurses serving in the role of clinical instructor on a DEU participated in the study. Content analyses were used to code and synthesize common theses from the interviews. The themes that emerged related to role perception were mentoring, ensuring competency with basic skills and tasks, and development of critical thinking in nursing clinical education. The themes related to perceived learning needs of staff nurses related to the role of clinical instructor were the need for clear objectives from the academic affiliate, more coordination and acknowledgement by the academic affiliate, and addition education in dealing with students with diverse learning needs and accommodations.


Subject(s)
Clinical Competence , Mentors , Nurse Clinicians/psychology , Thinking , Education, Nursing, Baccalaureate , Focus Groups , Humans , Interinstitutional Relations , Learning , Nurse's Role , Nursing Education Research , Qualitative Research
11.
JAMA Dermatol ; 152(7): 776-82, 2016 07 01.
Article in English | MEDLINE | ID: mdl-27050141

ABSTRACT

IMPORTANCE: Despite the unquestioned relationship of UV radiation (UVR) exposure and melanoma development, UVR-independent development of melanoma has only recently been described in mice. These findings in mice highlight the importance of the genetic background of the host and could be relevant for preventive measures in humans. OBJECTIVE: To study the role of the melanocortin-1 receptor (MC1R) and melanoma risk independently from UVR in a clinical setting. DESIGN, SETTING, AND PARTICIPANTS: Hospital-based case-control study, including genetic testing, questionnaires, and physical data (Molecular Markers of Melanoma Study data set) including 991 melanoma patients (cases) and 800 controls. MAIN OUTCOMES AND MEASURES: Association of MC1R variants and melanoma risk independent from sun exposure variables. RESULTS: The 1791 participants included 991 with a diagnosis of melanoma and 800 control patients (mean [SD] age, 59.2 [15.6] years; 50.5% male). Compared with wild-type carriers, carriers of MC1R variants were at higher melanoma risk after statistically adjusting for previous UVR exposure (represented by prior sunburns and signs of actinic skin damage identified by dermatologists), age, and sex compared with wild-type carriers (≥2 variants, OR, 2.13 [95% CI, 1.66-2.75], P < .001; P for trend <.001). After adjustment for sex, age, sunburns in the past, and signs of actinic skin damage, the associations remained significant (OR, 1.65 [95% CI, 1.02-2.67] for R/R, OR, 2.63 [95% CI, 1.82-3.81] for R/r; OR, 1.83 [95% CI, 1.36-2.48] for R/0; and OR, 1.50 [95% CI, 1.01-2.21] for r/r, with P values ranging from <.001 to .04 when adjusted for facial actinic skin damage; OR, 2.36 [95% CI, 1.62-3.43] for R/r; and OR, 1.47 [95% CI, 1.08-1.99] for R/0 with P values ranging from <.001 to .01 when adjusted for dorsal actinic skin damage; and OR, 2.54 [95% CI, 1.76-3.67] for R/r, OR, 1.75 [95% CI, 1.30-2.36] for R/0; and OR, 1.50 [95% CI, 1.02-2.20] for r/r with P values ranging from <.001 to .04 when adjusted for actinic skin damage on the hands). CONCLUSIONS AND RELEVANCE: Carriers of MC1R variants were at increased melanoma risk independent of their sun exposure. Further studies are required to elucidate the causes of melanoma development in these individuals.


Subject(s)
Melanoma/genetics , Receptor, Melanocortin, Type 1/genetics , Skin Neoplasms/genetics , Ultraviolet Rays/adverse effects , Adult , Aged , Back , Case-Control Studies , Face , Female , Genetic Testing , Genetic Variation , Hand , Humans , Keratosis, Actinic/etiology , Male , Middle Aged , Risk Factors , Sunburn/etiology , Surveys and Questionnaires
12.
Melanoma Res ; 25(5): 412-20, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26225579

ABSTRACT

CDKN2A is the most prominent familial melanoma gene, with mutations occurring in up to 40% of the families. Numerous mutations in the gene are known, several of them representing regional founder mutations. We sought to determine, for the first time, germline mutations in CDKN2A in Austria to identify novel mutations. In total, 700 individuals (136 patients with a positive family history and 164 with at least two primary melanomas as the high-risk groups; 200 with single primary melanomas; and 200 healthy individuals as the control groups) were Sanger sequenced for CDKN2A exon 1α, 1ß, and 2. The 136 patients with affected relatives were also sequenced for CDK4 exon 2. We found the disease-associated mutations p.R24P (8×), p.N71T (1×), p.G101W (1×), and p.V126D (1×) in the group with affected relatives and p.R24P (2×) in the group with several primary melanomas. Furthermore, we discovered four mutations of unknown significance, two of which were novel: p.A34V and c.151-4 G>C, respectively. Computational effect prediction suggested p.A34V as conferring a high risk for melanoma, whereas c.151-4 G>C, although being predicted as a splice site mutation by MutationTaster, could not functionally be confirmed to alter splicing. Moreover, computational effect prediction confirmed accumulation of high-penetrance mutations in high-risk groups, whereas mutations of unknown significance were distributed across all groups. p.R24P is the most common high-risk mutation in Austria. In addition, we discovered two new mutations in Austrian melanoma patients, p.A34V and c.151-4 G>C, respectively.


Subject(s)
Genes, p16 , Germ-Line Mutation , Melanoma/genetics , Skin Neoplasms/genetics , Adult , Aged , Amino Acid Substitution , Austria/epidemiology , Case-Control Studies , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Humans , Male , Melanoma/epidemiology , Middle Aged , Polymorphism, Single Nucleotide , Skin Neoplasms/epidemiology , Melanoma, Cutaneous Malignant
13.
Int J Cancer ; 135(7): 1625-33, 2014 Oct 01.
Article in English | MEDLINE | ID: mdl-24535833

ABSTRACT

We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma-specific survival (MSS). Results were combined using random effects meta-analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin-fixed paraffin-embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval (CI) 1.04-1.28, p = 0.005, eleven cohorts) and MSS (HR = 1.20 per allele, 95% CI 1.01-1.39, p = 0.03, eight cohorts). We report bioinformatic data supportive of a functional effect for rs2249844. Higher levels of PARP1 gene expression in tumors were shown to be associated with tumor ulceration and poorer OS.


Subject(s)
Genetic Predisposition to Disease , Melanoma/genetics , Melanoma/mortality , Poly(ADP-ribose) Polymerases/genetics , Polymorphism, Single Nucleotide/genetics , Quantitative Trait Loci , DNA, Neoplasm/genetics , Follow-Up Studies , Humans , Poly (ADP-Ribose) Polymerase-1 , Polymerase Chain Reaction , Prognosis , Retrospective Studies , Survival Rate
14.
Pigment Cell Melanoma Res ; 27(2): 234-43, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24219834

ABSTRACT

An association between low serum vitamin D levels and poorer melanoma survival has been reported. We have studied inheritance of a polymorphism of the GC gene, rs2282679, coding for the vitamin D-binding protein, which is associated with lower serum levels of vitamin D, in a meta-analysis of 3137 melanoma patients. The aim was to investigate evidence for a causal relationship between vitamin D and outcome (Mendelian randomization). The variant was not associated with reduced overall survival (OS) in the UK cohort, per-allele hazard ratio (HR) for death 1.23 (95% confidence interval (CI) 0.93, 1.64). In the smaller cohorts, HR in OS analysis was 1.07 (95% CI 0.88, 1.3) and for all cohorts combined, HR for OS was 1.09 (95% CI 0.93, 1.29). There was evidence of increased melanoma-specific deaths in the seven cohorts for which these data were available. The lack of unequivocal findings despite the large sample size illustrates the difficulties of implementing Mendelian randomization.


Subject(s)
Genetic Predisposition to Disease , Inheritance Patterns/genetics , Melanoma/genetics , Vitamin D-Binding Protein/genetics , Adolescent , Adult , Aged , Alleles , Cohort Studies , Genetic Association Studies , Haplotypes/genetics , Humans , Kaplan-Meier Estimate , Melanoma/blood , Meta-Analysis as Topic , Middle Aged , Polymorphism, Single Nucleotide/genetics , Skin Neoplasms , Sun Protection Factor , Treatment Outcome , Vitamin D/blood , Young Adult , Melanoma, Cutaneous Malignant
15.
Pigment Cell Melanoma Res ; 25(3): 384-94, 2012 May.
Article in English | MEDLINE | ID: mdl-22325793

ABSTRACT

Inherited MC1R variants modulate MITF transcription factor signaling, which in turn affects tumor cell proliferation, apoptosis, and DNA repair. The aim of this BioGenoMEL collaborative study in 10 melanoma cohorts was to test the hypothesis that inherited variants thereby moderate survival expectation. A survival analysis in the largest cohort (Leeds) was carried out adjusting for factors known to impact on survival. The results were then compared with data from nine smaller cohorts. The absence of any consensus MC1R alleles was associated with a significantly lower risk of death in the Leeds set (HR, 0.64; 95% CI, 0.46-0.89) and overall in the 10 data sets (HR, 0.78; 95% CI, 0.65-0.94) with some support from the nine smaller data sets considered together (HR, 0.83; 95% CI, 0.67-1.04). The data are suggestive of a survival benefit for inherited MC1R variants in melanoma patients.


Subject(s)
Genetic Variation , Melanoma/genetics , Melanoma/mortality , Receptor, Melanocortin, Type 1/genetics , Skin Neoplasms/genetics , Skin Neoplasms/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Follow-Up Studies , Genetic Predisposition to Disease , Hair Color/genetics , Humans , Inheritance Patterns/genetics , Male , Middle Aged , Survival Analysis , Young Adult
16.
Pigment Cell Melanoma Res ; 25(2): 234-42, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22145962

ABSTRACT

Sun exposure is causal for melanoma but is subject to bias of recall so that it is difficult to dissect the role of particular patterns of sun exposure. In this hospital-based case-control study (n = 1991), we aimed to analyze pigmentation traits and signs of actinic damage at different anatomic locations as markers of melanoma risk in central European patients. Although all signs of actinic damage (freckling, wrinkling and solar lentigos) were significantly associated with melanoma risk in multivariate logistic regression models adjusting for age and sex, the strongest associations were observed for the dorsal parts of the body: adjusted odds ratios [OR] were 4.22 for wrinkling on the neck, 3.43 for solar lentigos and 3.37 for freckling on the back (all P < 0.001), respectively. These associations were independent of age, sex and pigmentation traits. Our results indicate that signs of actinic damage are predictors of melanoma risk, particularly on the back.


Subject(s)
Melanoma/pathology , Organ Specificity/radiation effects , Skin Neoplasms/pathology , Skin/pathology , Skin/radiation effects , Ultraviolet Rays/adverse effects , White People , Case-Control Studies , Female , Humans , Male , Melanoma/classification , Middle Aged , Observer Variation , Odds Ratio , Phenotype , Pigmentation/radiation effects , Risk Factors , Skin Neoplasms/classification
17.
Nat Genet ; 41(8): 909-14, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19578363

ABSTRACT

In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 x 10(-10)). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.


Subject(s)
Carcinoma, Basal Cell/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Skin Neoplasms/genetics , Carcinoma, Basal Cell/complications , Carcinoma, Squamous Cell/genetics , Chromosomes, Human, Pair 7/genetics , Chromosomes, Human, Pair 9/genetics , Coronary Artery Disease/complications , Coronary Artery Disease/genetics , Genome-Wide Association Study , Humans , Keratin-5/genetics , Linkage Disequilibrium/genetics , Melanoma/pathology , Membrane Proteins/genetics , Molecular Sequence Data , Neoplasm Proteins/genetics , Skin Neoplasms/complications
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