ABSTRACT
To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide association study of 38.5 million single nucleotide polymorphisms (SNPs) and small indels identified through whole-genome sequencing of 2230 Icelanders. We imputed genotypes for 4208 BCC patients and 109 408 controls using Illumina SNP chip typing data, carried out association tests and replicated the findings in independent population samples. We found new BCC susceptibility loci at TGM3 (rs214782[G], P = 5.5 × 10(-17), OR = 1.29) and RGS22 (rs7006527[C], P = 8.7 × 10(-13), OR = 0.77). TGM3 encodes transglutaminase type 3, which plays a key role in production of the cornified envelope during epidermal differentiation.
Subject(s)
Antigens, Surface/genetics , Carcinoma, Basal Cell/genetics , GTP-Binding Protein Regulators/genetics , Genetic Variation , Germ-Line Mutation , Transglutaminases/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Germ Cells/metabolism , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Skin Neoplasms/genetics , Young AdultABSTRACT
Bicalutamide is a selective androgen receptor antagonist. To date, it has been used orally with good efficacy results, but not in mesotherapy. In our center, we assessed whether patients undergoing bicalutamide mesotherapy showed positive responses and tolerated the local administration of bicalutamide. Six premenopausal women, with a mean age of 35.7 years and clinical diagnosis of Olsen Grade II or III female androgenetic alopecia accompanied by significant seborrhea were treated with 1 ml bicalutamide 0.5% mesotherapy. Three monthly sessions were performed. A subtle improvement in hair density was described after the third session. The overall satisfaction of the patients with the treatment was 6.3, on a scale of 1-10. Premenopausal women require several therapeutic approaches to combat severe androgenetic alopecia. Our data showed that bicalutamide mesotherapy was well tolerated and welcomed by the patients; we, therefore, provide a new tool for the management of this pathology.
ABSTRACT
Introduction: Refractory cases of alopecia areata (AA) may be considered a therapeutic challenge. Intralesional methotrexate (IL-MTX) has been used in other dermatological diseases rather than AA. Likewise, its topical use as an immunosuppressant drug may be of interest for the control of the lymphoid infiltrate in AA. On the other hand, the use of fractional ablative laser is supported in literature as an alternative or complementary treatment in AA, whilst the generation of columns of thermal damage may favour the migration of cells and cytokines that are beneficial. Case Presentation: In this paper, we present 2 cases in which IL-MTX and ablative fractional CO2 laser were combined with excellent outcomes. Conclusion: Previous research encompasses a total of 23 patients. Most patients presented with patchy AA. The doses administered ranged from 2.5 to 50 mg with an average frequency of 3 weeks. On average, most patients required a minimum of 3 sessions. One case employed 1% topical methotrexate ointment. Adverse local events were mild and transient. In conclusion, the concomitant application of these treatments has not been reported previously. Specific recommendations relating to the appropriate dosing of the drug, frequency of administration, and requirements for analytical control studies should be determined in further studies.
ABSTRACT
We report a girl with lipophagic lobular panniculitis of unknown origin located on her ankles leading to circumferential fat atrophy of the ankles, a condition usually referred to as "annular lipoatrophy of the ankles." According to our patient's features and five additional cases reported so far, we conclude that this condition is actually an end-stage manifestation of an idiopathic lobular panniculitis of children localized to the lower part of the lower limbs. An association with some autoimmune manifestations is highlighted.
Subject(s)
Ankle , Connective Tissue Diseases/pathology , Panniculitis/pathology , Subcutaneous Fat/pathology , Adolescent , Atrophy , Biopsy , Female , HumansABSTRACT
In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.
Subject(s)
Carcinoma, Basal Cell/genetics , Caspase 8/genetics , GATA3 Transcription Factor/genetics , Homeodomain Proteins/genetics , Nuclear Proteins/genetics , Oncogene Proteins/genetics , Proteins/genetics , Skin Neoplasms/genetics , Transcription Factors/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Iceland , Male , Membrane Proteins , Middle Aged , N-Myc Proto-Oncogene Protein , White People/genetics , Young AdultABSTRACT
To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
Subject(s)
Genetic Predisposition to Disease , Germ-Line Mutation , Neoplasms/genetics , Tumor Suppressor Protein p53/metabolism , Humans , Polymorphism, Single Nucleotide , Tumor Suppressor Protein p53/geneticsABSTRACT
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.