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1.
J Invest Dermatol ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32920024

RESUMO

Despite growing public awareness on adverse consequences of excessive sun exposure, modifying sun-seeking behaviour is challenging as it appears to be driven by addictive mechanisms. This can have effects on health since sun exposure, although beneficial, when prolonged and repeated shows a causal relationship with skin cancer risk. Using data from 2,500 UK twins, we observed sun-seeking to be significantly heritable (h2≥58%). In a GWAS meta-analysis of sun-seeking behaviour in 261,915 subjects of European ancestry, we identified five GWAS-significant loci, previously associated with addiction, behavioural and personality traits, cognitive function and educational attainment, and enriched for central nervous system gene expression: MIR2113 (P=2.08×10-11), FAM76B/MTMR2/CEP57 (P=3.70×10-9), CADM2 (P=9.36×10-9), TMEM182 (P=1.64×10-8), and PLCL1/LINC01923/SATB2 (P=3.93×10-8). These findings imply that the behaviour concerning ultraviolet exposure is complicated by a genetic predisposition shared with neuropsychological traits. This should be taken into consideration when designing awareness campaigns and may help improving people's attitude toward sun exposure.

2.
BMJ ; 370: m2942, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878860

RESUMO

OBJECTIVE: To evaluate the associations between personal use of permanent hair dyes and cancer risk and mortality. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: 117 200 women enrolled in the Nurses' Health Study, an ongoing prospective cohort study of female nurses in the United States. The women were free of cancer at baseline, reported information on personal use of permanent hair dyes, and were followed for 36 years. EXPOSURE: Status, duration, frequency, and integral use (cumulative dose calculated from duration and frequency) of permanent hair dyes. Age at first use and time since first use of permanent hair dyes. MAIN OUTCOME MEASURES: Associations of personal use of permanent hair dyes with risk of overall cancer and specific cancers, and cancer related death. Age and multivariable adjusted hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazard models. RESULTS: Ever users of permanent hair dyes had no significant increases in risk of solid cancers (n=20 805, excluding non-melanoma skin cancers; hazard ratio 0.98, 95% confidence interval 0.96 to 1.01) or hematopoietic cancers overall (n=1807; 1.00, 0.91 to 1.10) compared with non-users. Additionally, ever users did not have an increased risk of most specific cancers (cutaneous squamous cell carcinoma, bladder cancer, melanoma, estrogen receptor positive breast cancer, progesterone receptor positive breast cancer, hormone receptor positive breast cancer, brain cancer, colorectal cancer, kidney cancer, lung cancer, and most of the major subclasses and histological subtypes of hematopoietic cancer) or cancer related death (n=4860; 0.96, 0.91 to 1.02). Basal cell carcinoma risk was slightly increased for ever users (n=22 560; 1.05, 1.02 to 1.08). Cumulative dose was positively associated with risk of estrogen receptor negative breast cancer, progesterone receptor negative breast cancer, hormone receptor negative breast cancer, and ovarian cancer. An increased risk of Hodgkin lymphoma was observed only for women with naturally dark hair (based on 70 women, 24 with dark hair), and a higher risk of basal cell carcinoma was observed for women with naturally light hair. CONCLUSION: No positive association was found between personal use of permanent hair dye and risk of most cancers and cancer related mortality. The increased risk of basal cell carcinoma, breast cancer (estrogen receptor negative, progesterone receptor negative, hormone receptor negative) and ovarian cancer, and the mixed findings in analyses stratified by natural hair color warrant further investigation.


Assuntos
Carcinoma de Células Escamosas/induzido quimicamente , Tinturas para Cabelo/efeitos adversos , Enfermeiras e Enfermeiros/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Adulto , Neoplasias Encefálicas/induzido quimicamente , Neoplasias da Mama/induzido quimicamente , Carcinoma Basocelular/induzido quimicamente , Estudos de Casos e Controles , Neoplasias Colorretais/induzido quimicamente , Feminino , Humanos , Neoplasias Renais/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Pessoa de Meia-Idade , Neoplasias Ovarianas/induzido quimicamente , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/mortalidade , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/induzido quimicamente
3.
Nat Hum Behav ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989287

RESUMO

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.

4.
Nat Commun ; 11(1): 820, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041948

RESUMO

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling 19,149 SCC cases and 680,049 controls. We discover eight novel loci associated with SCC, confirm all previously associated loci, and perform fine mapping of causal variants. The novel SNPs occur within skin-specific regulatory elements and implicate loci involved in cancer development, immune regulation, and keratinocyte differentiation in SCC susceptibility.


Assuntos
Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença/genética , Expressão Gênica , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Neoplasias Cutâneas/genética
5.
Pharmacoepidemiol Drug Saf ; 29(2): 161-172, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32017292

RESUMO

PURPOSE: This study aimed to systematically evaluate the association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and pancreatic safety in patients with type 2 diabetes mellitus (T2DM). METHODS: Electronic databases were searched before September 2019 to include randomized controlled trials (RCTs) of SGLT2 inhibitors that reported any event on pancreatitis or pancreatic cancer among patients with T2DM. Peto odds ratio (OR) with 95% confidence interval (CI) was used to pool the data. The GRADE framework was introduced to assess the quality of evidence. RESULTS: Of the 35 trials involving 44 912 patients with T2DM included, 41 events of acute pancreatitis (19 trials; 32 932 patients), 72 events of overall pancreatitis (including acute pancreatitis, chronic pancreatitis, or nonspecific pancreatitis; 26 trials; 36 688 patients), and 40 events of pancreatic cancer (18 trials; 27 806 patients) were reported during a median follow-up of 52 weeks. SGLT2 inhibitors were not associated with an increased risk of acute pancreatitis compared to controls (placebo or other active drugs; Peto OR, 1.13; 95% CI, 0.60-2.13; moderate quality evidence). A similar result was found for risk of overall pancreatitis (Peto OR, 1.08; 95% CI, 0.67-1.75; moderate quality evidence) and pancreatic cancer (Peto OR, 1.34; 95% CI, 0.71-2.54; very low-quality evidence). CONCLUSIONS: Moderate quality evidence from RCTs shows no significantly increased risk of acute pancreatitis associated with SGLT2 inhibitors, while there is very low-quality evidence suggesting no significant association between SGLT2 inhibitors and pancreatic cancer among patients with T2DM.

6.
Int J Cancer ; 146(9): 2394-2405, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

7.
Int J Cancer ; 147(1): 14-20, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593602

RESUMO

Elevated cutaneous nevus number has been linked to longer telomeres. Recently, a large systematic Mendelian randomization study identified a significant positive association between telomere length and risk of cancer. Here, we hypothesized that higher nevus count, as a phenotypic marker of longer telomere, may be associated with increased risk of internal cancer, and prospectively examined the association between nevus count and total as well as site-specific cancer risk among participants in the Nurses' Health Study (NHS, 1986-2012) and the Nurses' Health Study 2 (NHS2, 1989-2013) using Cox proportional hazards models. During 3,900,264 person-years of follow-up, we documented a total of 23,004 internal cancer cases (15,484 in the NHS and 7,520 in the NHS2). Compared to participants who had no nevi, the multivariate hazard ratios of total cancer (excluding skin cancer) were 1.06 (95% confidence interval [CI], 1.03-1.09) for women with 1-5 nevi, 1.08 (95% CI, 1.03-1.15) for those who had 6-14 nevi and 1.19 (95% CI, 1.05-1.35) for those with 15 or more nevi (p trend <0.0001). Moreover, because nevus count has been associated with risk of breast cancer previously, we conducted a secondary analysis by excluding breast cancer from the outcomes of interest. The results were very similar to those of our primary analysis. For individual cancer, most of the associations with nevus count were positive but not statistically significant. In conclusion, we identified the number of cutaneous nevi as a phenotypic marker associated with internal cancer risk, which may be explained by telomere biology.

8.
iScience ; 22: 423-429, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31816529

RESUMO

The gain bandwidth of a single-mode fiber is limited by the atomic transitions of one rare earth gain element. Here we overcome this long-standing challenge by designing a new single-mode fiber with multi-section core, where each section is doped with different gain element. We theoretically propose and experimentally demonstrate that this configuration provides a gain bandwidth well beyond the capability of conventional design, whereas the inclusion of multiple sections does not compromise single-mode operation or the quality of the transverse modal profile. This new fiber will be beneficial in realizing all fiber laser systems with few-cycle pulse duration or octave tunability.

9.
Epidemiology ; 30 Suppl 2: S10-S16, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31569148

RESUMO

BACKGROUND: Short telomere length (TL), an indicator of cellular aging and oxidative stress, has been implicated in glucose homeostasis. Additionally, studies have illustrated that the association of TL with health outcomes may vary by age. Yet, data on the association between TL and gestational diabetes mellitus (GDM) are sparse and the potential effect modification by age remains unknown. METHODS: We prospectively investigated TL in early pregnancy in relation to the subsequent GDM risk in a case-control study of 93 women with GDM and 186 randomly selected controls matched on age, race/ethnicity, and gestational weeks at blood collection. TL was measured using blood samples collected at 10-14 gestational weeks and reported as the T/S ratio, a ratio of telomere repeat length T to copy number of a single copy gene S. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusted for major risk factors. RESULTS: Overall, TL was not significantly associated with GDM risk. The TL-GDM association was significantly modified by age (Pinteraction = 0.02). Shorter TL in early pregnancy was associated with an increased GDM risk among women <30 years old (adjusted OR comparing the shortest vs. longest tertile: 3.1, 95% CI = 1.2, 8.1), but not associated with GDM risk among women ≥30 years. CONCLUSION: Our findings suggest that TL in early pregnancy may be implicated in GDM development, particularly among younger women.

10.
Oncotarget ; 10(19): 1760-1774, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30956756

RESUMO

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.

12.
BMJ ; 364: k4981, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606716

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Grandes/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Fumar/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Ex-Fumantes/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Razão de Chances , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Adulto Jovem
13.
JAMA Dermatol ; 155(3): 353-357, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30586131

RESUMO

Importance: Detection bias may influence the results of epidemiologic studies of skin cancer risk. An individual's degree of contact with the health care system, and, specifically, undergoing routine screening practices, may be a source of such bias. More intensive screening practices may be associated with increased diagnoses of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Objective: To assess a possible association between health care screening practices and skin cancer risk. Design, Setting, and Participants: The cohort of participants for this study was drawn from the Nurses' Health Study (121 700 women) and Health Professionals Follow-up Study (51 529 men). Participants in the Nurses' Health Study were followed up from June 1, 1990, to June 1, 2012, and participants in the Health Professionals Follow-up Study were followed up from January 1, 1990, to January 1, 2012. Statistical analysis was performed from April 4, 2017, to May 16, 2018. Exposures: During cohort follow-up, Nurses' Health Study and Health Professionals Follow-up Study participants were asked whether they had undergone various health care screening practices including physical examination by a physician, sigmoidoscopy or colonoscopy, eye examination, serum cholesterol test, mammography, breast examination and pelvic examination, and prostate-specific antigen test and rectal examination. Main Outcomes and Measures: Incident BCC, SCC, and invasive melanoma. Cases of SCC and melanoma were confirmed with histopathologic findings. Hazard ratios (HRs) with 95% CIs were calculated for the association between screening practices and the various types of skin cancer. Results: This study included 77 736 women from the Nurses' Health Study (mean [SD] age at baseline, 56 [7] years) who were followed up for 1 388 523 person-years and 39 756 men from the Health Professionals Follow-up Study (mean [SD] age at baseline, 58 [10] years) who were followed up for 635 319 person-years. A total of 14 319 incident BCCs, 1517 SCCs, and 506 melanomas were identified in the Nurses' Health Study cohort and 8741 incident BCCs, 1191 SCCs, and 469 melanomas were identified in the Health Professionals Follow-up Study cohort. Positive associations were seen between various screening practices and diagnoses of BCC and SCC, with similar directions of associations seen with melanoma for some screening practices. In the Nurses' Health Study, the multivariable HR associated with undergoing a physical examination was 1.46 (95% CI, 1.30-1.64) for BCC, 2.32 (95% CI, 1.41-3.80) for SCC, and 1.66 (95% CI, 0.85-3.22) for melanoma. Similar results were seen in the Health Professionals Follow-up Study, with a multivariable HR associated with undergoing a physical examination of 1.43 (95% CI, 1.26-1.63) for BCC and 1.85 (95% CI, 1.17-2.92) for SCC, with an attenuated HR for melanoma of 1.04 (95% CI, 0.64-1.69). Conclusions and Relevance: Undergoing health care screening practices increases the likelihood of being diagnosed with skin cancer. Researchers should be aware of this association and, where appropriate and possible, condition analyses of skin cancer risk on measures of health care use, including screening, to address confounding associated with detection bias.


Assuntos
Carcinoma Basocelular/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Programas de Rastreamento/métodos , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Viés , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia
14.
J Am Acad Dermatol ; 80(2): 500-507.e10, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30130598

RESUMO

BACKGROUND: Current evidence about the association between voriconazole and risk of cutaneous squamous cell carcinoma (SCC) remains inconsistent. OBJECTIVE: To assess the association between voriconazole use and risk of SCC. METHODS: We systematically searched PubMed and Embase and performed a random effects model meta-analysis to calculate the pooled relative risk (RR) with a 95% confidence interval (CI). RESULTS: Of the 8 studies involving a total of 3710 individuals with a lung transplant or hematopoietic cell transplant that were included in the qualitative analysis, 5 were included in the meta-analysis. Use of voriconazole was significantly associated with increased risk of SCC (RR, 1.86; 95% CI, 1.36-2.55). The increased risk did not differ according to type of transplantation or adjustment for sun exposure. Longer duration of voriconazole use was found to be positively associated with risk of SCC (RR, 1.72; 95% CI, 1.09-2.72). Voriconazole use was not associated with increased risk of basal cell carcinoma (RR, 0.84; 95% CI, 0.41-1.71). LIMITATIONS: There were some heterogeneities in the retrospective observational studies. CONCLUSIONS: Our findings support an increased risk of SCC associated with voriconazole in individuals with a lung transplant or hematopoietic cell transplant. Routine dermatologic surveillance should be performed, especially among individuals at high risk of developing SCC.


Assuntos
Antifúngicos/efeitos adversos , Carcinoma de Células Escamosas/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Pulmão/efeitos adversos , Neoplasias Cutâneas/induzido quimicamente , Voriconazol/efeitos adversos , Antifúngicos/uso terapêutico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/fisiopatologia , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Transplante de Pulmão/métodos , Masculino , Estudos Observacionais como Assunto , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/fisiopatologia , Voriconazol/uso terapêutico
15.
Cancer ; 125(7): 1133-1142, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30548236

RESUMO

BACKGROUND: The incidence of nonmelanoma skin cancer (NMSC) exceeds the incidence of all other types of cancers combined. Cumulative sun exposure and intermittent sun exposure are known risk factors for the development of NMSC. Because obesity has been shown to decrease the risk of NMSC incidence, this study investigated whether the risk of NMSC with sun exposure was consistent across different levels of body size. METHODS: Body size was assessed with the body mass index (BMI) and the waist-to-hip ratio (WHR). Sun exposure was assessed in watts and langleys and by the amount of time spent outdoors per day in the summer during a person's 30s. RESULTS: Among 71,645 postmenopausal women eligible for inclusion in this study, 13,351 participants (18.6%) developed NMSC. A BMI ≥ 25 kg/m2 or a WHR ≥ 0.80 was associated with lower NMSC hazard rates (hazard ratio for BMI, 0.78; hazard ratio for WHR, 0.89); however, the association between higher levels of sun exposure and a higher risk of NMSC was more apparent among women with a BMI ≥ 25 kg/m2 or a WHR ≥ 0.80 in comparison with those of a normal weight (P for interaction for BMI < .001; P for interaction for WHR = .022). CONCLUSIONS: Although most studies have considered sun exposure as a covariate, none have addressed the potential interaction of body size with sun exposure; therefore, the effect size of being overweight or obese may have been overestimated. In comparison to the normal-weight group, those in the overweight group had increasingly higher hazard rates with increasing sun exposure. Further studies are warranted to investigate how increased weight interacts with sun exposure to influence skin cancer pathogenesis.


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Obesidade/epidemiologia , Neoplasias Cutâneas/epidemiologia , Luz Solar , Idoso , Índice de Massa Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Sobrepeso/epidemiologia , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia , Relação Cintura-Quadril
16.
Nat Commun ; 9(1): 4774, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30429480

RESUMO

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.


Assuntos
Grupo com Ancestrais do Continente Europeu/genética , Pleiotropia Genética/genética , Melanoma/genética , Nevo Pigmentado/genética , Neoplasias Cutâneas/genética , Proteínas de Transporte/genética , Citocromo P-450 CYP1B1/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Fosfolipases A2 do Grupo VI/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Histona Desacetilases/genética , Humanos , Fatores Reguladores de Interferon/genética , MicroRNAs/genética , Proteínas dos Microfilamentos/genética , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , RNA/genética , Proteínas de Ligação a RNA , Receptores Acoplados a Proteínas-G/genética , Proteínas Repressoras/genética , Fator de Células-Tronco/genética , Telomerase/genética , Proteínas de Ligação a Telômeros/genética
17.
Diabetes Obes Metab ; 20(12): 2919-2924, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30039616

RESUMO

A slight increase in melanoma risk was observed among sodium-glucose co-transporter-2 (SGLT-2) inhibitor users in the regular reports. However, the association remains uncertain. To address this issue, we performed a systematic search of electronic databases up to May 2, 2018 and a meta-analysis of 21 randomized controlled trials (RCTs) involving 20 308 patients. We did not find a significant increase in risk of melanoma among SGLT-2 inhibitor users (Peto odds ratio [OR], 2.17; 95% confidence interval [CI], 0.80-5.89; I2 , 0%). Similar results were observed in the subgroup analyses according to the type of SGLT-2 inhibitor, type of control, ages of patients, race/ethnicity, and trial durations. For non-melanoma skin cancer risk, no significant difference was observed when all trials were combined (Peto OR, 0.70; 95% CI, 0.47-1.07; I2 , 0%), while a significantly decreased risk was observed among trials with duration <52 weeks (Peto OR, 0.12; 95% CI, 0.02-0.59; I2 , 0%). No evidence of publication bias was detected in the analyses. Current evidence from RCTs did not support a significantly increased risk of skin cancer associated with SGLT-2 inhibitors.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Melanoma/etiologia , Neoplasias Cutâneas/etiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Neoplasias Cutâneas/epidemiologia
18.
Genet Epidemiol ; 42(6): 571-586, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29968341

RESUMO

The human MC1R gene is highly polymorphic among lightly pigmented populations, and several variants in the MC1R gene have been associated with increased risk of both melanoma and nonmelanoma skin cancers. The functional consequences of MC1R gene variants have been studied in vitro and in vivo in postulated causal pathways, such as G-protein-coupled signaling transduction, pigmentation, immune response, inflammatory response, cell proliferation, and extracellular matrix adhesion. In a case-control study nested within the Nurses' Health Study, we utilized hierarchical modeling approaches, incorporating quantitative information from these functional studies, to examine the association between particular MC1R alleles and the risk of skin cancers. Different prior matrices were constructed according to the phenotypic associations in controls, cell surface expression, and enzymatic kinetics. Our results showed the parameter variance estimates of each single nucleotide polymorphism (SNP) were smaller when using a hierarchical modeling approach compared to standard multivariable regression. Estimates of second-level parameters gave information about the relative importance of MC1R effects on different pathways, and odds ratio estimates changed depending on prior models (e.g., the change ranged from -21% to 7% for melanoma risk assessment). In addition, the estimates of prior model hyperparameters in the hierarchical modeling approach allow us to determine the relevance of individual pathways on the risk of each of the skin cancer types. In conclusion, hierarchical modeling provides a useful analytic approach in addition to the widely used conventional models in genetic association studies that can incorporate measures of allelic function.


Assuntos
Predisposição Genética para Doença , Modelos Genéticos , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 1 de Melanocortina/genética , Neoplasias Cutâneas/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
19.
Cancer Manag Res ; 10: 1143-1154, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29795986

RESUMO

Purpose: Melanoma represents an important public health problem, due to its high case-fatality rate. Identification of individuals at high risk would be of major interest to improve early diagnosis and ultimately survival. The aim of this study was to evaluate whether MC1R variants predicted melanoma risk independently of at-risk phenotypic characteristics. Materials and methods: Data were collected within an international collaboration - the M-SKIP project. The present pooled analysis included data on 3,830 single, primary, sporadic, cutaneous melanoma cases and 2,619 controls from seven previously published case-control studies. All the studies had information on MC1R gene variants by sequencing analysis and on hair color, skin phototype, and freckles, ie, the phenotypic characteristics used to define the red hair phenotype. Results: The presence of any MC1R variant was associated with melanoma risk independently of phenotypic characteristics (OR 1.60; 95% CI 1.36-1.88). Inclusion of MC1R variants in a risk prediction model increased melanoma predictive accuracy (area under the receiver-operating characteristic curve) by 0.7% over a base clinical model (P=0.002), and 24% of participants were better assessed (net reclassification index 95% CI 20%-30%). Subgroup analysis suggested a possibly stronger role of MC1R in melanoma prediction for participants without the red hair phenotype (net reclassification index: 28%) compared to paler skinned participants (15%). Conclusion: The authors suggest that measuring the MC1R genotype might result in a benefit for melanoma prediction. The results could be a valid starting point to guide the development of scientific protocols assessing melanoma risk prediction tools incorporating the MC1R genotype.

20.
Cancer Med ; 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29761859

RESUMO

Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a crucial role in predicting survival for Hepatocellular carcinoma (HCC) patients. This study aims to capture the current research hotspots of HCC, based on the analysis of publications related to HCC research from 2013 to 2017, and to identify a novel lncRNA signature for HCC prognosis through the data mining in The Cancer Genome Atlas (TCGA). "Prognosis" and "biomarker" were located in the core of the HCC research hotspot. Moreover, long noncoding RNA was the top one research frontier in HCC research. The associations between survival outcome and the expression of lncRNAs were evaluated by the univariate and multivariate Cox proportional hazards regression analyses. Four lncRNAs (LINC00261, TRELM3P, GBP1P1, and CDKN2B-AS1) were identified as significantly correlated with overall survival (OS). These four lncRNAs were gathered as a single prognostic signature. There was a significant positive correlation between HCC patients with low-risk scores and overall survival (HR = 1.802, 95%CI [1.224-2.652], P = .003). Further analysis suggested that the prognostic value of this four-lncRNA signature was independent in clinical features. The enrichment analysis of prognostic lncRNA-related gene was performed to find out the related pathways. Our study indicates that this novel lncRNA expression signature may be a useful biomarker of the prognosis for HCC patients, based on bioinformatics analysis.

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