RESUMO
BACKGROUND AND PURPOSE: Research indicates that patients with myotonic dystrophy type 1 (DM1) are at increased risk of cancer and early death. Family data may provide insights given DM1 phenotypic heterogeneity, the broad range of non-muscular manifestations and the usual delays in the diagnosis of DM1. METHOD: Family history data were collected from 397 genetically and/or clinically confirmed DM1 patients (respondents) enrolled in the US or UK myotonic dystrophy registries. Standardized mortality ratios were calculated for DM1 first-degree relatives (parents, siblings and offspring) by their reported DM1 status (affected, unaffected or unknown). For cancer-related analyses, mixed effects logistic regression models were used to evaluate factors associated with cancer development in DM1 families, including familial clustering. RESULTS: A total of 467 deaths and 337 cancers were reported amongst 1737 first-degree DM1 relatives. Mortality risk amongst relatives reported as DM1-unaffected was comparable to that of the general population [standardized mortality ratio (SMR) 0.82, P = 0.06], whilst significantly higher mortality risks were noted in DM1-affected relatives (SMR = 2.47, P < 0.0001) and in those whose DM1 status was unknown (SMR = 1.60, P < 0.0001). In cancer risk analyses, risk was higher amongst families in which the DM1 respondent had cancer (odds ratio 1.95, P = 0.0001). Unknown DM1 status in the siblings (odds ratio 2.59, P = 0.004) was associated with higher cancer risk. CONCLUSION: There is an increased risk of death, and probably cancer, in relatives with DM1 and in those whose DM1 status is unknown. This suggests a need to perform a careful history and physical examination, supplemented by genetic testing, to identify family members at risk for DM1 and who might benefit from disease-specific clinical care and surveillance.
Assuntos
Distrofia Miotônica/epidemiologia , Neoplasias/epidemiologia , Análise por Conglomerados , Família , Feminino , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/genética , Distrofia Miotônica/mortalidade , Neoplasias/genética , Neoplasias/mortalidade , Exame Físico , Sistema de Registros , Medição de Risco , Inquéritos e Questionários , Análise de Sobrevida , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: Recent studies have suggested a possible excess risk of skin neoplasms in patients with myotonic dystrophy (DM). Risk factors related to this observation have not been defined. METHOD: Information regarding personal history of skin tumors, pigmentation phenotype, and skin reaction to sun exposure were collected from 266 DM patients who were enrolled in the US National Institutes of Health National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members. RESULTS: Seventy-seven subjects reported having skin tumors that were either benign (n = 31), malignant (n = 32) or both (n = 14). Female gender [odds ratio (OR) = 2.27, 95% confidence interval (CI) 1.02-5.05, P = 0.04], older age (OR = 1.10, 95% CI 1.05-1.16, P < 0.001) and DM1 subtype (OR = 3.42, 95% CI 1.27-9.26, P = 0.02) were associated with a malignant skin tumor. The associations between malignant skin tumors and known risk factors [light eye color (OR = 1.62, 95% CI 0.78-3.39, P = 0.20), light skin complexion (OR = 1.31, 95% CI 0.63-2.73, P = 0.48) and moderate/extensive face freckles (OR = 1.47, 95% CI 0.50-4.34, P = 0.49)] were modest. Strong, but not statistically significant, associations were noted with sunburn reactions when exposed to sunlight (OR = 4.28, 95% CI 0.91-19.95, P = 0.06, and OR = 2.19, 95% CI 0.67-7.09, P = 0.19, for sunburn with and without blistering, respectively). CONCLUSIONS: Although our study was limited by small sample size, the risk factors for malignant skin tumors in DM strongly resemble the general population. It is recommended that DM patients adhere to sun exposure protective behavior.
Assuntos
Melanose/epidemiologia , Distrofia Miotônica/epidemiologia , Sistema de Registros , Neoplasias Cutâneas/epidemiologia , Pigmentação da Pele/fisiologia , Queimadura Solar/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Patients with myotonic dystrophy (DM) are at high risk of brain cancer. This study describes the spectrum of brain neoplasms in DM patients. METHODS: Data from 1119 DM patients identified from the National Swedish Patient Register between 1987 and 2007 were linked to the National Cancer and the Cause of Death Registers. Standardized incidence ratios (SIRs) and cumulative incidence to quantify the relative and absolute risks of brain neoplasms were calculated and the Kaplan-Meier estimator was used for survival analysis. Patient follow-up started at birth or the age at the start of Swedish cancer registration (1 January 1958) and ended at the age of brain neoplasm diagnosis, death or on 31 December 2007. RESULTS: Twenty patients developed brain neoplasm during follow-up {median age 53, range 2-76 years, accounting for a five-fold excess risk of brain tumors during the patient lifetime [SIR = 5.4, 95% confidence interval (CI) 3.4-8.1, P = 1 × 10(-5) ]}. Astrocytoma was the most common histological subtype (n = 16, 80%), and almost all cases (n = 19) developed after age 20. No statistically significant differences in gender-specific risks (SIR in men 6.3 and in women 3.8, P-heterogeneity 0.46) were observed. After accounting for competing mortality related to DM, the cumulative incidence of brain neoplasms reached 2.9% (95% CI 1.8%-4.7%) by age 70. Five-year survival after brain tumor diagnosis was 52% (95%CI 29%-75%) overall (number at risk 8) and 34% (95% CI 26%-47%) for malignant neoplasms (number at risk 5). CONCLUSION: Despite the high relative risk of DM-related brain tumors, the absolute risk is modest. Nonetheless, careful evaluation of DM patients with new central nervous system symptoms is warranted.
Assuntos
Astrocitoma/epidemiologia , Neoplasias Encefálicas/epidemiologia , Distrofia Miotônica/epidemiologia , Sistema de Registros , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Suécia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown. METHODS: We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry. RESULTS: We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR)=10.5, 95% confidence interval=5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia=4; brain tumour=3; acute lymphoblastic leukaemia=2; rhabdomyosarcoma=2; and neuroblastoma=1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4. CONCLUSIONS: These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours.
Assuntos
Síndrome de Costello/genética , Displasia Ectodérmica/genética , Insuficiência de Crescimento/genética , Cardiopatias Congênitas/genética , Neoplasias/epidemiologia , Síndrome de Noonan/genética , Proteínas ras/genética , Adolescente , Criança , Pré-Escolar , Síndrome de Costello/patologia , Displasia Ectodérmica/patologia , Fácies , Insuficiência de Crescimento/patologia , Feminino , Mutação em Linhagem Germinativa , Alemanha/epidemiologia , Cardiopatias Congênitas/patologia , Humanos , Lactente , Masculino , Neoplasias/etiologia , Neoplasias/patologia , Síndrome de Noonan/patologia , Sistema de Registros , Fatores de Risco , Transdução de SinaisRESUMO
BACKGROUND: The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. METHODS: We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. RESULTS: Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007). CONCLUSION: Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.
Assuntos
Biomarcadores Tumorais/genética , Cromossomos Humanos Par 9/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Metanálise como Assunto , PrognósticoRESUMO
Three genome-wide association studies of testicular cancer have uncovered predisposition alleles in or near KITLG, BAK1, SPRY4, TERT, ATF7IP and DMRT1. We investigated whether testicular cancer-risk alleles can be utilized in the clinical setting. We employed the receiver operating characteristic curves for genetic risk models to measure the discriminatory power of a risk variant-based risk model, and found that the newly discovered variants provided a discriminatory power of 69.2%. This suggested that about 69.2% of the time, a randomly selected patient with testicular cancer had a higher estimated risk than the risk for a randomly selected control subject. Using a multiplicative model, we estimated that white men in the top 1% of genetic risk as defined by eight risk variants had a relative risk that was 10.5-fold greater than that for the general white male population. This risk differential does not appear to be clinically useful, given the relative rarity and highly curable nature of testicular germ cell tumour (TGCT). In the authors' view, a stratified genetic risk assessment strategy might be useful, theoretically, for men who also have independent clinical risk factors for testicular cancer. Several established TGCT risk factors, such as cryptorchidism (RR=4.8) and male infertility (SIR=2.8) might prove useful in that context, but we currently do not know whether these testicular cancer-risk loci are associated with, or independent of, such clinical risk factors. More research is required before we can utilize testicular cancer-risk loci for clinically meaningful risk prediction.
Assuntos
Predisposição Genética para Doença , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/genética , Mapeamento Cromossômico , Criptorquidismo , Estudo de Associação Genômica Ampla , Humanos , Infertilidade , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias Testiculares/patologiaRESUMO
BACKGROUND: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. METHODS: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. RESULTS: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P = 0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P = 0.5) mutation carriers. CONCLUSION: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.
Assuntos
Proteínas de Ligação a DNA/genética , Genes BRCA1 , Genes BRCA2 , Heterozigoto , Mutação , Polimorfismo de Nucleotídeo Único , Estudos de Coortes , Feminino , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: The TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. METHODS: To investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. RESULTS: No association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93-1.10, P(trend)=0.77; MDM2: HR=0.96, 95%CI: 0.84-1.09, P(trend)=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87-1.12, P(trend)=0.83; MDM2: HR=0.98, 95%CI: 0.80-1.21, P(trend)=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. CONCLUSION: There was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers.
Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Genes p53 , Predisposição Genética para Doença , Mutação , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-mdm2/genética , Neoplasias da Mama/etiologia , Feminino , Heterozigoto , Humanos , Fatores de RiscoRESUMO
Testicular germ cell tumors are comprised of two histologic groups, seminomas and non-seminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable levels of net endogenous DNA damage. To test our hypothesis, we conducted a case-case analysis of 51 seminoma and 61 non-seminoma patients using data and specimens from the Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort. A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modelled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with non-seminoma compared with seminoma (OR(50th percentile) = 3.31, 95% CI: 1.00, 10.98; OR(75th percentile) = 3.71, 95% CI: 1.04, 13.20; p for trend = 0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR(50th percentile) = 2.27, 95% CI: 0.75, 6.87; OR(75th percentile) = 2.40, 95% CI: 0.75, 7.71; p for trend = 0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that net endogenous levels are higher in patients who develop non-seminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.
Assuntos
Dano ao DNA , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Ensaio Cometa/métodos , Intervalos de Confiança , DNA , Dano ao DNA/genética , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Seminoma/genéticaRESUMO
Testicular germ cell tumours (TGCT) cluster in families, but responsible genes remain unidentified. The association between testicular microlithiasis (TM) and testicular carcinoma in situ (CIS) suggests that TM may be a TC risk factor. We report testicular ultrasound findings in men with familial TGCT (FTGCT) and their unaffected relatives. A total of 81 men (48 affected and 33 unaffected) from 31 families with > or =2 TC cases underwent testicular ultrasound. Testicular microlithiasis was defined as either 'classic' (> or =5 microliths) or 'limited' (<5 microliths). Statistical analyses used Fisher's exact test and permutation testing. Testicular microlithiasis was more frequent in the contralateral testicles of men with a history of TGCT (affected men) than in unaffected men (48 vs 24%, P=0.04). The association appeared stronger for classic TM (21 vs 9%) than for limited TM (27 vs 15%). Testicular microlithiases were bilateral in six out of seven (87%) unaffected men. Among affected men, TM was not associated with histology, age at diagnosis or cancer treatment. Of the 31 families, 10 accounted for a majority (61%) of the TM cases identified (P=0.11). Testicular microlithiasis was more prevalent among FTGCT family members than described previously in the general population, and was more common among FTGCT cases vs unaffected blood relatives. Testicular microlithiasis appeared to cluster in certain families. These findings suggest both a familial predisposition to TM and an association between TM and FTGCT. If proven, this could be clinically important to men in FTGCT families, and may be useful in identifying specific genes involved in FTGCT.
Assuntos
Litíase/epidemiologia , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Doenças Testiculares/epidemiologia , Neoplasias Testiculares/epidemiologia , Adulto , Comorbidade , Família , Humanos , Masculino , PrevalênciaRESUMO
BACKGROUND: Clinically relevant genetics knowledge is essential for appropriate assessment and management of inherited cancer risk, and for effective communication with patients. This national physician survey assessed knowledge regarding basic cancer genetics concepts early in the process of introduction of predictive genetic testing for breast/ovarian and hereditary non-polyposis colorectal cancer (HNPCC) syndromes. METHODS: A stratified random sample was selected from the American Medical Association Masterfile of all licensed physicians. In total, 1251 physicians (820 in primary care, 431 in selected subspecialties) responded to a 15 minute questionnaire (response rate 71%) in 1999-2000. Multivariate logistic regression analyses were conducted to identify demographic and practice characteristics associated with accurate response to three knowledge questions. RESULTS: Of the study population, 37.5% was aware of paternal inheritance of BRCA1/2 mutations, and 33.8% recognised that these mutations occur in <10% of breast cancer patients. Only 13.1% accurately identified HNPCC gene penetrance as >or=50%. Obstetrics/gynaecology physicians, oncologists, and general surgeons were significantly more likely than general and family practitioners to respond accurately to the breast/ovarian questions, as were gastroenterologists to the HNPCC question. CONCLUSIONS: These nationally representative data indicate limited physician knowledge about key cancer genetics concepts in 1999-2000, particularly among general primary care physicians. Specialists were more knowledgeable about syndromes they might treat or refer elsewhere. Recent dissemination of practice guidelines and continued expansion of relevant clinical literature may enhance knowledge over time. In addition to educational efforts to assist physicians with the growing knowledge base, more research is needed to characterise the organisational changes required within the healthcare system to provide effective cancer genetics services.
Assuntos
Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias Ovarianas/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , MédicosRESUMO
Traditionally, cisplatin has not been regarded among chemotherapeutic drugs as a carcinogenic risk to humans because it is not a classical alkylating agent. A review of recently published experimental data indicates that cisplatin is mutagenic, clastogenic, capable of inducing cell transformation, able to act as an initiator in classical mouse skin initiation/promotion experiments, and carcinogenic in laboratory animals. Notably, it causes myeloid leukemia in BD IX rats. These observations demonstrate that cisplatin should be considered a potent carcinogen in experimental settings. A review of the literature identified 65 instances of subsequent cancer in patients receiving cisplatin-based chemotherapy for an initial malignancy. The majority of second cancers were acute nonlymphocytic leukemias or myelodysplasia. In only one instance was cisplatin the sole antineoplastic drug given to patients. The routine use of cisplatin in conjunction with other known or suspected human carcinogens makes it impossible to use these anecdotal reports as a basis for assessing cisplatin's carcinogenicity in humans. Two quantitative epidemiologic studies have addressed this question: One suggested that the combination of cisplatin and doxorubicin is leukemogenic in humans, while the other implicated etoposide rather than cisplatin as the leukemogen. Formal epidemiologic studies of appropriate cohorts of cisplatin-treated patients are needed to resolve the question of its carcinogenicity in humans.
Assuntos
Cisplatino/efeitos adversos , Neoplasias/induzido quimicamente , Animais , Carcinógenos/toxicidade , Cromossomos/efeitos dos fármacos , Cisplatino/toxicidade , DNA/efeitos dos fármacos , Humanos , Mutagênicos/toxicidade , Neoplasias/genética , Segunda Neoplasia Primária/induzido quimicamenteRESUMO
U. S. mortality and incidence statistics for nasopharyngeal cancer showed a fourfold excess risk of sarcomas in white children under age 10, and a fourfold to sevenfold excess of carcinomas in teen-age blacks. Mortality from nasopharyngeal carcinomas in young people was greater in the South than in the North, with the excess mortality in blacks linked to rural residence and low socioeconomic status. These and other characteristics of nasopharyngeal carcinoma in young persons suggested that environmental (perhaps infectious) agents are involved in this age group. These patterns contrasted with nasopharyngeal carcinomas developing after age 25, when the rates predominated in Chinese Americans. Nasopharyngeal cancer in the United States had three age peaks, with racial and epidemiologic distinctions that seemed to reflect different etiologies.
Assuntos
Carcinoma/epidemiologia , Neoplasias Nasofaríngeas/epidemiologia , Grupos Raciais , Sarcoma/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Povo Asiático , População Negra , Carcinoma/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/etiologia , Rabdomiossarcoma/epidemiologia , Rabdomiossarcoma/etiologia , População Rural , Sarcoma/etiologia , Fatores Socioeconômicos , Estados Unidos , População BrancaRESUMO
Among 4,869 patients with chronic lymphocytic leukemia (CLL) from the series of the End Results Program of the National Cancer Institute, Bethesda, Maryland, second primary cancers developed in 234 patients, compared to 204.9 expected. The risk was significantly elevated for malignant melanoma, soft-tissue sarcomas, and lung cancer. The frequency of rectal cancer was also elevated, but not significantly. The excess risk for these specific sites persisted throughout the period of follow-up, suggesting a susceptibility state that complicated the leukemic process rather than suggesting methodologic, diagnostic, or therapeutic effects. Immunologic defects to CLL may be involved in the etiology of excess risk for these sites, because a similar array of nonlymphoid tumors was seen following therapeutic immunosuppression among renal transplant recipients.
Assuntos
Imunidade , Leucemia Linfoide/imunologia , Neoplasias Primárias Múltiplas/etiologia , Neoplasias do Colo/etiologia , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Melanoma/etiologia , Neoplasias Primárias Múltiplas/imunologia , Neoplasias Retais/etiologia , Risco , Sarcoma/etiologia , Neoplasias Cutâneas/etiologia , Neoplasias de Tecidos Moles/etiologia , Fatores de TempoRESUMO
As part of a systematic program to evaluate the late effects of antineoplastic therapy in randomized clinical trials, patients enrolled in the low-dose thio-TEPA (TSPA) and 5-fluoro-2'-deoxyuridine (FdUrd) adjuvant colorectal cancer protocols of the Veterans Administration (VA) Surgical Oncology Group between 1958 and 1964 were studied. All patients received surgery with curative intent; 470 also received TSPA, 176 received FdUrd, and 867 received surgery only. The unique VA system permitted complete follow-up through 1977, with 10,902 person-years of observation accrued among 1,613 male patients (mean survival = 6.8 yr). Expected mortality and cancer incidence were computed by applying U.S. Mortality Statistics and Connecticut Tumor Registry age-, race-, sex-, and calendar time-specific rates to the person-years of observation. The mortality experience of the 3 groups was similar. Overall, there was a significant excess in total mortality (observed/expected = 1,359/553) attributable mainly to colorectal cancer (584/14), arteriosclerotic heart disease (258/215.9), pneumonia (41/17), gastric and duodenal ulcers (15/4), and cirrhosis (14/6). No excess mortality from noncolorectal cancers was apparent, nor were there significant differences by treatment: TSPA (22/22), FdUrd (9/12), and surgery only (50/42). Among 1,402 white patients, no significant excess of incident noncolorectal cancers were observed among patients treated with TSPA (30/31, FdUrd (14/15), or surgery only (63/58). Seven incident cases of leukemia developed (4.1 expected) among all patients of various groups: TSPA (3/1.3), FdUrd (1/0.6), and surgery only (3/2.2). No excess of new primary cancers was observed among 211 nonwhite patients. An inverse relationship between the occurrence of second primary cancer and age at diagnosis, irrespective of therapy, was suggested. The results demonstrated the feasibility of this approach for assessment of late complications of anticancer therapy and suggested no measurable carcinogenic effect following very low doses of TSPA and FdUrd in a population of this size.
Assuntos
Neoplasias do Colo/terapia , Floxuridina/efeitos adversos , Neoplasias Primárias Múltiplas/etiologia , Neoplasias Retais/terapia , Tiotepa/efeitos adversos , Adulto , Idoso , Ensaios Clínicos como Assunto , Neoplasias do Colo/mortalidade , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Retais/mortalidadeRESUMO
Recent case reports have suggested that the acquired immunodeficiency syndrome (AIDS) may be associated with cancers other than Kaposi's sarcoma (KS). We have used the population-based registries of the Surveillance, Epidemiology, and End Results (SEER) Program to examine these relationships on a statistical basis by comparing the morbidity odds ratio (OR) and 95% confidence interval (CI) for specific cancer sites in pre- and post-AIDS time periods. Among never-married 20- to 49-year-old men, a surrogate group representing homosexual men, significant increases in the morbidity OR's for KS between 1973-80 and 1981-82 were apparent in the San Francisco standard metropolitan statistical area (OR: 51.8; CI: 18.6-143.6) and in other areas covered by the SEER Program (OR: 18.6; CI: 2.2-154.5). Furthermore, a significant increase was found in the morbidity OR for Burkitt-like lymphoma in the San Francisco metropolitan area (OR: 9.1; CI: 1.8-45.6). In San Francisco County (which includes the City of San Francisco), there was a 2,043-fold increase in the morbidity OR for KS and a fivefold increase for Burkitt-like lymphomas, but there were no significant changes for other cancers between 1973-79 and 1982. Similarly, no significant changes in morbidity OR's were observed for other cancers in the remaining SEER registries. These findings provided statistical support for the excess risk of Burkitt-like lymphoma in a group at risk of AIDS.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Neoplasias/epidemiologia , Adulto , California , Humanos , Leucemia/epidemiologia , Linfoma/epidemiologia , Masculino , Casamento , Pessoa de Meia-Idade , Neoplasias/etiologia , Sistema de Registros , Risco , Sarcoma de Kaposi/epidemiologiaRESUMO
Immune reactivity to melanoma extracts was measured by the leukocyte adherence inhibition (LAI) test in 40 members of 3 melanoma-prone families. The melanoma patients had a wide range of responsiveness to the extract, the highest responder being a 10-year survivor. As a group, family members (including spouses) without disease had significantly elevated LAI responses compared to those of unrelated controls (P less than 0.01). Within the families, members with close exposure to melanoma patients for 10 years or more had a significantly higher response to melanoma antigen than did members with 0-5 years of close exposure (P less than 0.05). Responses of spouses and members at high risk of developing melanoma (B-K mole syndrome) also correlated with length of exposure to patients, which suggests that the elevated LAI response was not genetically determined. The high frequency of positive responses to melanoma antigens in these families, particularly in spouses, suggests the presence of transmissible melanoma-associated material capable of immunizing persons in contact with melanoma patients.
Assuntos
Antígenos de Neoplasias/administração & dosagem , Imunidade , Melanoma/etiologia , Neoplasias Cutâneas/etiologia , Feminino , Humanos , Teste de Inibição de Aderência Leucocítica , Masculino , Linhagem , Lesões Pré-Cancerosas/etiologia , Fatores de TempoRESUMO
The incidence of Kaposi's sarcoma (KS) was examined with the use of data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. KS is a manifestation of the recent epidemic of acquired immunodeficiency syndrome (AIDS) that has occurred particularly among homosexual men. The incidence of KS in 1973-79 was found to be higher (0.29 male and 0.07 female cases/100,000/yr) than is usually cited for the pre-AIDS KS incidence rates. Collectively, the 9 SEER registries in the United States showed only a slight increase in the incidence of KS between 1973-79 and 1980-81. However, the SEER registry covering San Francisco, which is a high-risk area for AIDS, showed a marked excess of KS in 1981. The KS case rate among never-married men younger than 50 years old, a surrogate index of homosexuality, was found to be markedly elevated in the post-AIDS period, compared with the case rate of a reference disease, mycosis fungoides. Never-married men younger than 50 years old, therefore, constitute a SEER-identifiable population who can be monitored for risk of KS and other neoplasms that might be related to AIDS. In addition, the incidence rate of KS in the SEER registry of Puerto Rico was generally higher than that in the U.S. SEER registries, despite data that suggested that KS may be underreported. The demographic characteristics of patients diagnosed as having KS in Puerto Rico suggested the classical rather than the AIDS-related form of KS.
Assuntos
Micose Fungoide/epidemiologia , Sarcoma de Kaposi/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Fatores Etários , Feminino , Humanos , Masculino , Casamento , Pessoa de Meia-Idade , National Institutes of Health (U.S.) , Porto Rico , Sistema de Registros , Fatores Sexuais , Estados UnidosRESUMO
Sixty members of 4 families prone to cutaneous malignant melanoma (CMM) and a genetically determined precursor nevus syndrome underwent extensive immunologic evaluation. The most consistent finding was a diminished in vitro response to pooled alloantigens in the one-way mixed leukocyte culture (MLC) and a tendency to low T-lymphocyte and B-lymphocyte levels. When compared to controls, low B-lymphocyte levels and reduced MLC responses were found not only in family members with CMM and/or precursor nevi but also in unaffected blood relatives and spouses. The genesis of the immune dysfunction and its possible relationship to melanoma pathogenesis remain to be clarified.
Assuntos
Imunidade , Melanoma/etiologia , Neoplasias Cutâneas/etiologia , Linfócitos B , Feminino , Humanos , Contagem de Leucócitos , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Masculino , Melanoma/sangue , Linhagem , Lesões Pré-Cancerosas/etiologia , Neoplasias Cutâneas/sangue , Linfócitos TRESUMO
We evaluated the occurrence of second cancers among 517 patients with non-Hodgkin's lymphoma (NHL) treated at the National Cancer Institute. Nine cases of acute nonlymphocytic leukemia (ANL) were observed compared to 0.08 cases expected (ratio of observed to expected cases, 105; 95% confidence limits, 48; 199). The excess risk of ANL was 4.1 cases per 1000 patients per year; the cumulative risk of ANL at 10 years was 7.9 +/- 3.2% (S.E.). A case-control study within the NHL cohort revealed that patients treated with both radiation and chemotherapy were at greater risk of ANL than were patients who received single-modality therapy (relative risk, 6.0; p less than 0.05), especially if the therapy included total-body or hemibody radiation. A positive correlation between cumulative radiation dose to the bone marrow and risk of ANL was demonstrated, independent of chemotherapy duration. A similar correlation between chemotherapy dose and risk of ANL was suggested but could not be proven with the available data. An apparent association between ANL risk and indolent NHL histological subtypes was due to the significantly larger amounts of potentially leukemogenic therapy to which these patients were repeatedly exposed. Only one case of ANL occurred among NHL patients whose initial therapy produced a durable complete remission. Our data are compatible with a multistep model of leukemogenesis and also underscore the need for curative NHL treatment regimens which minimize the duration and quantity of therapy required for optimum patient management.