RESUMEN
BACKGROUND: Aim of the study was to estimate the possibility of prognosis incidence by means of degrees of cancer aggravated family history. PATIENTS AND METHODS: 1233 families (n = 4689) from the Moscow Cancer Family Registry who answered 5-years later the first questionnaire were divided into 4 groups according to our classification of degrees of cancer aggravated family history: (1) not aggravated, (2) little aggravated, (3) aggravated, (4) syndromes (see detailed description in the text). The methods of genetic epidemiology, epidemiology, statistics were used. RESULTS: Incidence in the first and second groups were near population expected cases, some higher in the aggravated group and sharp rise in women from the syndromes-associated families (the most syndromes predisposed to cancer of women reproductive system), relative risk was 10.76 for probands and 8.19 for the first relative women. There was no increase infrequency of new cases among men in syndrome-associated families. CONCLUSION: Analysis of degrees of cancer aggravated family history can be used for the incidence prognosis; one or two cancer cases among first degree relations don't regard as a high oncogenetic risk factor; members of families with syndromes are obligatory cancer risk group.
Asunto(s)
Síndromes Neoplásicos Hereditarios , Linaje , Femenino , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Masculino , Moscú/epidemiología , Neoplasias/diagnóstico , Neoplasias/epidemiología , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/epidemiología , Pronóstico , Sistema de Registros , Factores de RiesgoRESUMEN
Chronic sodium nitrite (SN) treatment potentiated spontaneous and 1,2-dimethylhydrazine (DMH)-induced carcinogenesis. Mice injected with SN alone showed a higher incidence of leukemia and lung cancer than in controls. Combined treatment with DMH and SN induced most of benign and malignant tumors (hepatic hemangioendothelioma, hepatocarcinoma, renal adenoma, etc.). The difference in the numbers of DMH- and SN-induced tumor bearers was not significant until a concentration of 500 mg/l was reached (64.7%). The level of multiple tumor incidence increased when SN 50 and 500 mg/l was used. Unlike DMH alone, cumulative incidence of DMH-specific tumors and leukemia after combined treatment was higher. An evaluation of cumulative incidence and relative risk established an indirect but positive correlation between SN dose, on the one hand, and spontaneous and induced carcinogenesis, on the other. The strongest carcinogenic effect was reported when DMH was used in combination with SN 500 mg/l. Our data confirmed the carcinogenic hazard of chronic exposure to SN which increased when in combination with that to a specific carcinogenic substance.
Asunto(s)
1,2-Dimetilhidrazina/toxicidad , Carcinógenos/toxicidad , Cocarcinogénesis , Leucemia/inducido químicamente , Neoplasias Pulmonares/inducido químicamente , Nitrito de Sodio/toxicidad , Animales , Sinergismo Farmacológico , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBARESUMEN
The Familial Cancer Register, Moscow, established in 1990, has a record of pedigrees of 6,000 cancer patients. The records on the probands and families have been studied since 1995. The paper presents the data of a repeat survey of the families conducted in 1990-1995. Only 794 out of 3,000 families, included in the first survey, responded. Relapse was reported in 135 probands and/or relatives from 108 families. The following subgroups were identified depending on the rates of cancer morbidity in familial histories (the criteria are presented): 1) no incidence; 2) few cases; (3) more cases, and (4) all family members have cancer. New tumors were detected in one-third of such families. A direct correlation was found between the morbidity rates and neoplasia incidence. In 12 families of group 3, originally, not all the members had tumors.
Asunto(s)
Neoplasias/epidemiología , Neoplasias/genética , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Federación de Rusia/epidemiologíaRESUMEN
Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominantly inherited cancer predisposition which is linked to heterozygous mutations in mismatch repair genes. HNPCC tumour cells, in which the remaining wild-type copy of the mismatch repair gene is inactivated, display instability of microsatellite markers reflecting a defect in mismatch repair. Recently, patients carrying either one of two distinct germline mutations in the MLH1 and PMS2 genes were reported to accumulate somatic mutations of microsatellites in untransformed cells. One of the mechanisms that might account for this phenomenon was a dominant negative effect of the mutant allele. To evaluate this possibility, we examined a different family carrying one of the mutations (deletion of codon 618K in the MLH1 gene) which has been suspected to induce genetic instability in untransformed cells. No mutations in dinucleotide repeat markers were observed in a large number of lymphoblast clones derived from a carrier. Evidence for the deletion of the wild-type allele in two different tumours suggested that the inactivation of both gene copies was required for tumour initiation. These results indicate that the MLH1 618K deletion mutation alone does not necessarily cause marked mismatch repair deficiency in the presence of a wild-type allele.
Asunto(s)
Adenosina Trifosfatasas , Enzimas Reparadoras del ADN , Reparación del ADN , Proteínas de Unión al ADN , Heterocigoto , Síndromes Neoplásicos Hereditarios/genética , Proteínas Adaptadoras Transductoras de Señales , Proteínas Portadoras , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Análisis Mutacional de ADN , ADN de Neoplasias/análisis , Femenino , Mutación de Línea Germinal , Humanos , Masculino , Repeticiones de Microsatélite , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/genética , Proteínas Nucleares , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa , Proteínas/genética , Proteínas Proto-Oncogénicas/genéticaRESUMEN
Hereditary nonpolyposis colon cancer (HN-PCC) is an autosomally inherited predisposition to cancer that has recently been linked to defects in the human mismatch repair genes hMSH2 and hMLH1. The identification of the causative mutations in HNPCC families is desirable, since it confirms the diagnosis and allows the carrier status of unaffected relatives at risk to be determined. We report six different new mutations identified in the hMSH2 and hMLH1 genes of Russian and Moldavian HNPCC families. Three of these mutations occur in CpG dinucleotides and lead to a premature stop codon, a splicing defect or an amino-acid substitution in an evolutionary conserved residue. Analysis of a compilation of published mutations including our new data suggests that CpG dinucleotides within the coding regions of the hMSH2 and hMLH1 genes are hotspots for single base-pair substitutions.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Islas de CpG/genética , Proteínas de Unión al ADN , Mutación , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Adaptadoras Transductoras de Señales , Secuencia de Bases , Proteínas Portadoras , Exones/genética , Femenino , Humanos , Masculino , Moldavia , Datos de Secuencia Molecular , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS , Proteínas Nucleares , Linaje , Federación de RusiaRESUMEN
Basal-cell nevus was diagnosed in a 60-year-old patient who suffered for 20 years from multiple basal-cell carcinomas. Autopsy has revealed congenital absence of the right kidney and ureter after his death at the age of 61.
Asunto(s)
Síndrome del Nevo Basocelular/patología , Riñón/anomalías , Neoplasias Cutáneas/patología , Síndrome del Nevo Basocelular/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/diagnóstico , Uréter/anomalíasRESUMEN
The distribution of blood groups AB0, Rh, P1, MN and Haptoglobins among ovarian cancer patients was studied. Significant associations between ovarian cancer and B(III) and MN blood groups as well as the 2-1 variant of haptoglobin were revealed. These data should be kept in mind when forming the high risk groups among population, in relation to ovarian cancer.
Asunto(s)
Marcadores Genéticos , Neoplasias Ováricas/genética , Antígenos de Grupos Sanguíneos/genética , Femenino , Haptoglobinas/genética , HumanosRESUMEN
Medico-genetic examinations of 122 patients with multiple and/or early-onset basalioma revealed 5 cases of basal cell nevus syndrome. Clinical data on 5 probands and 3 first-degree relatives with the syndrome are presented.
Asunto(s)
Síndrome del Nevo Basocelular/diagnóstico , Carcinoma Basocelular/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Cutáneas/genética , Adolescente , Adulto , Anciano , Síndrome del Nevo Basocelular/genética , Carcinoma Basocelular/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/genéticaRESUMEN
A study of individual and family histories of 200 ovarian cancer patients and 200 healthy controls was concerned with evaluation of 274 factors of risk. It yielded 36 most informative ones. An 80% credibility of screening results was demonstrated when a combination of characteristics was used. Decision rule is recommended as a test for formation of a group at high risk.
Asunto(s)
Neoplasias Ováricas/etiología , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/genética , RiesgoRESUMEN
The frequency of several kinds of cancer among relatives of 200 patients with ovarian cancer was analysed. The annual population incidence was used as a control. Nonrandom familial clustering of ovarian cancer (p less than 0.01) was observed. The frequency of breast cancer in women and that of eosophagal cancer in man was higher than the expected value (p less than 0.05). The risk of ovarian cancer occurrence amounted 9% in women of the first degree of relationship, whereas cumulative risk in a population only reached 1.57% to the age of 90. The patterns of distribution of patients in the pedigrees satisfied the requirements of the multifactorial model. Heritability coefficient was 54.12 +/- 2.49%. Thus, women of the first degree of relationship compose the high risk group.
Asunto(s)
Genética de Población , Neoplasias Ováricas/genética , Adolescente , Adulto , Factores de Edad , Anciano , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Moscú , Neoplasias/epidemiología , Neoplasias/genética , Neoplasias Ováricas/epidemiología , Fenotipo , Riesgo , Población UrbanaRESUMEN
A family with five ovarian neoplasms in three subsequent generations was studied. Four women had ovarian cancer at age 38, 40, 47, and 53, and one had cystoma ovari at 24. There were other neoplasms and preneoplastic lesions in this family. Several developmental anomalies were revealed, and one of them (a tooth anomaly) may be associated with ovarian tumors. Cytogenetic studies have been carried out on six of the living relatives, including two treated for ovarian neoplasms. The incidence of spontaneous chromosome aberrations was not significantly increased in each of these cases. Polymorphism of constitutive heterochromatin regions was observed in all six individuals. The possible type of inheritance of the ovarian cancer, the significance of the tooth anomaly, and the constitutive heterochromatin polymorphism as cancer markers in this family are discussed.
Asunto(s)
Carcinoma/genética , Neoplasias Ováricas/genética , Bandeo Cromosómico , Femenino , Humanos , Incisivo/anomalías , Cariotipificación , Neoplasias Ováricas/complicaciones , Linaje , Anomalías Dentarias/complicacionesRESUMEN
Two families with high incidence of ovarian cancer among the 1st and 2nd degree relatives are described. These were four sisters suffering it in one family (K). In the other family (L) but the proband her mother and two mother's sisters had ovarian cancer. A daughter of the proband at the age of 24 had surgically removed cystoma of the left ovary. In this family in all women with ovarian tumors as well as in their other two relatives congenital teeth anomalies were observed.