Effect of smoking on breast cancer in carriers of mutant BRCA1 or BRCA2 genes

BACKGROUND: Smoking has carcinogenic effects, and possibly antiestrogenic effects as well, but it has not been found to be a risk factor for breast cancer in women in the general population. However, hereditary breast cancer is primarily a disease of premenopausal women, and interactions between genes and hormonal and environmental risk factors may be particularly important in this subgroup. METHODS: We conducted a matched case-control study of breast cancer among women who have been identified to be carriers of a deleterious mutation in either the BRCA1 or the BRCA2 gene. These women were assessed for genetic risk at one of several genetic counseling programs for cancer in North America. Information about lifetime smoking history was derived from a questionnaire routinely administered to women who were found to carry a mutation in either gene. Smoking histories of case subjects with breast cancer and age-matched healthy control subjects were compared. Odds ratios for developing breast cancer were determined for smokers versus nonsmokers by use of conditional logistic regression for matched sets after adjustment for other known risk factors. RESULTS: Subjects with BRCA1 or BRCA2 gene mutations and breast cancer were significantly more likely to have been nonsmokers than were subjects with mutations and without breast cancer (two-sided P = .007). In a multivariate analysis, subjects with BRCA1 or BRCA2 mutations who had smoked cigarettes for more than 4 pack-years (i.e., number of packs per day multiplied by the number of years of smoking) were found to have a lower breast cancer risk (odds ratio = 0.46, 95% confidence interval = 0.27-0.80; two-sided P = .006) than subjects with mutations who never smoked. CONCLUSIONS: This study raises the possibility that smoking reduces the risk of breast cancer in carriers of BRCA1 or BRCA2 gene mutations.     

Mutation process in mini-satellites

Minisatellites are tandemly repeated DNA sequences with repeat units in the range 6-100 bp. They are preferentially located in subtelomeric euchromatin of chromosomes of higher eukaryotes. Minisatellite loci frequently show variability in allele length. This variability is a consequence of high frequency of mutations which change repeat copy number of locus. The most part of minisatellite mutations are germline specific and possibly meiotic. Examples of different mutations and involved genomic mechanisms are reviewed in this paper. A possible biological role of minisatellites is discussed.     

Radical prostatectomy for localized prostatic carcinoma in a renal transplant patient

A case of multiple pyogenic granuloma affecting the penis of a 28 year old man is reported. The lesions were arranged in a floret-like fashion around the inner aspect of the prepuce and developed after circumcision for congenital phimosis. Histopathological examination of sections from a biopsy specimen of the papillomatous growths revealed the findings of pyogenic granuloma. In this patient, the pathogenesis of the lesions is probably related to the failure in surgical wound repair that followed circumcision. Problems of clinical and histopathological differential diagnosis are discussed.     

Hyperexpression of the multiple drug resistance gene (MDR-1) in chronic myeloleukemia patients

AIM: To elucidate prognostic value of MDR-1 gene expression in patients with chronic myeloid leukemia (CML). MATERIALS AND METHODS: The MDR-1 gene expression was studied by in situ hybridization in hemopoietic cells of 63 Ph-positive CML patients in different phases of the disease. The survival of the patients and duration of the chronic phase (CP) were evaluated using the Caplan-Meyer method. RESULTS: MDR-1-positive patients had a shorter survival (p < 0.01) and CP (p < 0.05) than negative ones. MDR-1 gene overexpression has no impact either on the survival or duration of AP and BP (p < 0.05). Moreover, the MDR-1 gene overexpression is not dependent either on the previous treatment or other prognostic markers. CONCLUSION: Overexpression of MDR-1 gene is an independent prognostic factor and an additional parameter to Sokal's scores.     

Lack of evidence for a polymorphism at codon 160 of human O6-alkylguanine-DNA alkyltransferase gene in normal tissue and cancer

O6-benzylguanine (BG) is a potent, specific inactivator of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which enhances sensitivity to nitrosoureas in cells and tumor-bearing animals. BG is presently undergoing clinical trials for development as an agent to enhance the therapeutic index of alkylating agent chemotherapy. It has been reported that a polymorphism exists in the human agt gene, with about 15% of the Japanese population having arginine at codon 160 instead of glycine on the polypeptide (Y. Imai et al., Carcinogenesis, 16: 2441-2445, 1995). The resultant mutant AGT protein is equally effective against both methylated DNA as compared with wild type protein. However, this mutant AGT protein was less sensitive to inactivation by BG with a 20-fold increase in the ED50 value. This observation raised the possibility that a subpopulation of patients may be resistant to BG due to a single base change. We have demonstrated that this alteration also reduces the sensitivity to O6-benzyl-8-oxoguanine, an equally potent, yet much longer-lived human metabolite of BG. To test the possibility that this germ-line mutation of the agt gene might explain resistance to BG and O6-benzyl-8-oxoguanine of patients on our Phase I clinical trials, we evaluated the DNA from lymphocytes of 18 patients. The G160R mutation was not found in any of the 18 patients. To determine the frequency of this mutation in the United States population, DNA from 181 healthy individuals were investigated and, again, the mutation was not observed in this cohort. Therefore, if the mutation exists, it is in statistically <1.6% of the United States noncancerous population. To investigate the possibility that this mutation might be somatic, we evaluated genomic DNA samples from 94 human primary cancers of four different histological subtypes (brain, colon, esophageal, and head and neck). Again, none were found to have the G160R mutation.     

Epidemiologic-hygienic aspects of the assessment of carcinogenic risk in methacrylate production

The authors studied oncologic mortality among the workers exposed to some acryl monomers. The oncologic risk was estimated for the individuals exposed to acrylonitrile, methyl methacrylate, methyl- and butyl acrylate, methacrylic acid. Occurrence of the malignancies appeared to depend on the dose of methyl methacrylate.     

The potentials of indirect calorimetry in the differential assessment of the metabolic status of obese patients with insulin-independent diabetes mellitus

Twenty-one obese patients with non-insulin dependent diabetes mellitus, 16 female and 5 male ones, were fed similar isocaloric rations, differing only by the share of substitution of the traditional protein products (0%, 60%, 30%, 45%) in the Danpro-S, Danpro-Fibre soybean protein concentrate. The parameters tested were daily glycemia, C-peptides, blood hydrocortisone, and urinary excretion of nitrous metabolites. Indirect calorimetry was used to assess the protein, fat, and carbohydrate oxidation rates at rest. Addition of proteins of a plant origin to the diets of such patients was associated with significant changes of the energy metabolism at rest at the expense of increased oxidation of carbohydrates and reduced protein catabolism, that may be regarded as a favorable effect. In this patient population a 30% soybean diet brings about an almost maximal positive effect in patients with the first degree of obesity, whereas in those with the second degree of obesity such effect is attained by the 45% soybean diet.