RESUMO
BACKGROUND: Prostate cancer (PC) risk increases with African ancestry and a history of sexually transmitted infections (STIs). Also, single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes influence PC risk. This pilot study explores interactions between STIs and TLR-related SNPs in relation to PC risk among Jamaican men. METHODS: This case-control study evaluates two TLR related SNPs in 356 Jamaican men (194 controls and 162 cases) with or without history of STIs using stepwise penalized logistic regression in multivariable analyses. RESULTS: Age (odds ratio [OR] = 1.08; 95% confidence interval [CI]: 1.04-1>.12; p < .001) and IRF3_rs2304206 GG genotype (OR = 0.47; 95% CI: 0.29-0<.78; p = .003) modulated PC risk in people with history of STIs. In the population with no history of STIs, resulting interactions between risk factors did not survive correction for multiple hypothesis testing. CONCLUSION: Overall, an interaction between the IFR3_rs2304206 variant and a history of exposure to STIs leads to greater decrease of PC risk than the presence of polymorphic genotype alone. These findings are suggestive and require further validation. Identification of gene variants along with detection of lifestyle behaviors may contribute to identification of men at a greater risk of PC development in the population.
Assuntos
Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/etiologia , Infecções Sexualmente Transmissíveis/complicações , Receptores Toll-Like/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Jamaica , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de RiscoRESUMO
African ancestry and obesity are associated with higher risk of prostate cancer (PC). In a pilot study, we explored interactions between obesity (as measured by waist to hip ratio (WHR)) and inflammatory SNPs in relation to PC risk among Jamaican men. This study evaluated 87 chemokine and cytokine associated SNPs in obese and normal weight cases (N=109) and controls (N=102) using a stepwise penalized logistic regression approach in multivariable analyses. Upon stratification by WHR (normal weight (WHR<0.90) or obese (WHR≥0.90)), inheritance of CCR6 rs2023305 AG+GG (OR=1.75, p=0.007), CCR9 rs7613548 AG+GG (OR=1.71, p=0.012) and IL10ra rs2229113 AG+GG (OR=1.45, p=0.01) genotypes was associated with increase in overall or low grade (Gleason score<7) PC risk among normal weight men. These odds were elevated among obese men who possessed the CCR5 rs1799987 AG+GG (OR=1.95, p=0.003) and RNASEL rs12135247 CT+TT genotypes (OR=1.59, p=0.05). CCR7 rs3136685 AG+GG (p=0.032) was associated with a 1.52-1.70 fold increase in the risk of high grade cancer (Gleason score≥7) among obese men. CCR7 variant emerged as an important factor associated with high grade PC risk among obese men in our analyses. Overall, genetic loci found significant in normal weight men were not significant in obese men and vice-versa, partially explaining the role of obesity on PC risk among black men. Also, older age was an important risk factor both in normal weight and obese men but only with regard to low grade PC. Associations of inflammatory SNPs with obesity are suggestive and require further validation in larger cohorts to help develop an understanding of PC risk among obese and non-obese men of African descent.
Assuntos
Tamanho Corporal , Obesidade/complicações , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra/genética , Estudos de Casos e Controles , Quimiocinas/genética , Citocinas/genética , Interação Gene-Ambiente , Humanos , Mediadores da Inflamação , Jamaica , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias da Próstata/etiologia , Fatores de RiscoRESUMO
We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1-2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1-2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1-10) and 14 (range 6-37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linfonodos/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Axila/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática/patologia , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fatores de Risco , Biópsia de Linfonodo Sentinela , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: High-risk (HR) HPV genotypes other than 16 and 18 have been detected in a significant proportion of immunocompromised females. We aim to evaluate the frequency of HR HPV genotypes in a population of HIV-positive Caribbean women. METHODS: One hundred sixty-seven consecutive, non-pregnant, HIV-positive females ≥18 years were recruited in this study. Each participant received a vaginal examination, PAP smear, and completed a questionnaire. DNA was extracted for HPV testing in 86 patients. RESULTS: Mean age was 39.1 years for women positive for HR HPV and 43.1 years for women negative for HR HPV (P value â=â0.040). 78% (130/167) of the women had HR HPV infections; the prevalence of abnormal cervical cytology was 38% among women who were HR HPV-positive compared to women who were HR HPV-negative (22%). Fifty-one percent of the 86 women with available genotype carried infections with HPV 16 and/or HPV 18; genotypes of unknown risk were also frequently observed. Women who had a CD4+ count of ≤200 had 7 times increased odds of carrying HR HPV infection in comparison to women with CD4+>200. CONCLUSIONS: HR HPV infections in HIV infected females may consist of more than just HPV 16 and 18, but also HPV 52 and 58. Further studies are needed to determine whether HPV 52 and 58 play a significant role in the development of cervical cytological abnormalities in HIV+ women.
Assuntos
Coinfecção/virologia , Infecções por HIV/virologia , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Infecções por Papillomavirus/virologia , Adulto , Idoso , Bahamas/epidemiologia , Colo do Útero/patologia , Colo do Útero/virologia , Coinfecção/epidemiologia , Feminino , Genótipo , Infecções por HIV/epidemiologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Prevalência , Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
OBJECTIVES: We evaluated whether pancreatic main duct fluid can provide protein biomarkers with prognostic value. METHODS: Mass spectrometry proteomics was applied to as little as 20µL of fluid collected at the time of tumor surgical resection. Biomarker proteins identified for 27 patients were correlated with clinical outcomes. RESULTS: Thirteen patients had pancreatic ductal adenocarcinomas, 4 had intraductal papillary mucinous neoplasm with in situ adenocarcinoma, 5 had ampullary adenocarcinomas, 2 had intraductal papillary mucinous neoplasms, and 3 had benign diseases. In pathologic stage II or higher pancreatic ductal adenocarcinoma, moderate or high expression of S100A8 or S100A9 proteins was associated with a median disease recurrence-free survival of 5.8 months compared with 17.3 months in patients with low expression (P = 0.002). Median overall survival was 12.6 versus 27 months for patients with moderate to high versus low S100A8 and A9 expression (P = 0.02). CONCLUSIONS: This analysis suggests distinct proteomic signatures for pancreatic cancer. Patients in our study with elevated levels of S100A8 or A9 in the ductal fluid, a near absence of pancreatic enzymes, and high levels of mucins were found to have significantly worse prognosis. Although further validation is needed to corroborate these findings, analysis of pancreatic ductal fluid is a promising tool for identifying biomarkers of interest.
Assuntos
Biomarcadores Tumorais/metabolismo , Calgranulina A/metabolismo , Calgranulina B/metabolismo , Mucinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Humanos , Estimativa de Kaplan-Meier , Espectrometria de Massas/métodos , Recidiva Local de Neoplasia , Suco Pancreático/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Proteoma/metabolismo , Proteômica/métodosRESUMO
BACKGROUND: Free tissue transfer from an abdominal donor site has become a popular method for postmastectomy breast reconstruction. The detrimental effects of adjuvant chemotherapy on healing and the resulting clinical impact on patient outcome remains somewhat unclear for abdominal bulges and hernias resulting after free tissue transfer from the abdominal donor site. METHODS: An institutional review board-approved retrospective review of 155 free muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps performed for breast reconstruction was undertaken to evaluate the effect of adjuvant chemotherapy on abdominal donor-site morbidity. The primary outcome studied was the development of hernias and bulges. Statistical analysis was performed using univariate and multivariate classification and regression tree (CART) analysis. RESULTS: Of the 155 patients, 51 underwent bilateral MS-TRAM flaps and 104 underwent unilateral MS-TRAM flap reconstruction. Thirty-nine patients underwent adjuvant chemotherapy. A statistically significant association was seen between chemotherapy treatment and the incidence of hernias alone (P < 0.05; odds ratio, 6.42; 95% confidence interval, 0.88-73.58). Multivariable CART analyses corroborated these findings and revealed that presence of diabetes mellitus (DM), bilaterality, and receiving chemotherapy treatment were related to increased incidence of hernias (P = 0.011, 0.005, and 0.017, respectively) after controlling for clinical variables such as smoking status, chronic obstructive pulmonary disease, and type of closure. Univariate analyses also revealed a statistically significant association between bilaterality in conjunction with chemotherapy treatment and the incidence of hernias alone (P = 0.0002; odds ratio, 37.56; 95% confidence interval, 4.56-476.35). This highly significant finding is further augmented by multivariable CART analyses, which found that patients who were bilateral and underwent chemotherapy treatment or those with DM were significantly more likely to develop hernias (P < 0.001 and P = 0.016, respectively). CONCLUSIONS: To date, our study is the single largest series of abdominal donor-site complications in patients receiving chemotherapy and free MS-TRAM breast reconstruction. We have demonstrated an increase in the incidence of abdominal donor-site complications, specifically abdominal bulges and hernias, in patients undergoing chemotherapy for advanced stages of breast cancer. This increased complication rate is most pronounced in patients requiring chemotherapy who undergo bilateral reconstruction, and is also a significant risk for patients receiving chemotherapy who have preexisting DM.