[Mammography--a potential factor in breast cancer etiology].
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This article is a report on long-term followup of a total of 44 serious gynecomastia cases in the stages I-III (according to Deutinger). The treatment consisted of either a semicircular incision and subcutaneous mastectomy or a superiorly or an inferiorly based nipple transposition while performing male reduction mammoplasty. Aesthetically pleasing results could be obtained by a periareolar approach and mastectomy. This inconspicuous procedure is feasible even in massive gynecomastia cases (stage III) or in cases of male breast asymmetry. On the other hand, all cases with breast reduction plasty and nipple transposition resulted in wing-shaped, mainly broad scars, and subjectively unfavorable results. Consequently, we favor the semicircular approach in male reduction mammoplasty in treating serious gynecomastias. With regard to possible male breast cancer etiology, the histological specimen of the mammary gland in gynecomastia is excised prior to any additional liposuction for supplementary body contouring.
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To examine the hypothesis that familial breast cancer risk is related to estrogen metabolism, we analyzed urines of daughters of breast cancer patients and their matched controls for estrone (E1), estradiol (E2), and estriol (E3). From this, we computed estriol proportions (E3/E1 + E2 + E3). "Patient-daughters" and the matched controls showed no differences in estriol proportions. Our results failed to support the hypothesis that high-risk women (those with a family history of breast cancer) have relatively lower estriol proportions, and we concluded that whatever family history contributes to breast cancer risk, that risk is not likely to be transmitted by the estrogen profile.
Of the 120 cases of mammary cancer occurring in 117 female dogs (15 spayed), 2 male dogs, and 1 dog of undetermined sex, 107 (nearly 90%) were observed in dogs 8 to 15 years old. Mammary tumors occurred in nearly 14% of 875 female dogs with neoplasms. Nearly 60% of 128 neoplasms were located in the 4th and 5th mammary glands. Of the 128 cancers in these 120 dogs, 85 were classified as duct carcinoma, 38 as lobular carcinoma, 3 as malignant mixed tumor, and 2 as duct and lobular carcinomas. Most duct carcinomas originated in the epithelial cells of ducts at all levels, and a few arose in previously benign duct papillomas. The lobular carcinomas arose in alveoli and developed into progressively larger lobules. A negative factor in the development of mammary cancer is ovariectomy before or shortly after the first estrous cycle in the dog and before the age of 40 in women. In both dog and man, aging is a positive factor in the development of mammary cancer. In women, other positive factors are nulliparity and inheritance; e.g., a high rate of breast cancer in close female relatives of Jewish extraction. An epidemiologic study of breast cancer in man and dog in high-risk countries(e.g., United States) and low-risk countries (e.g., Japan) is indicated.
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The urine of 26 otherwise healthy women with fibrocystic disease of the breast was assayed by gas chromatography for testosterone and androstanediol (5alpha-androstane-3alpha, 17beta-diol), the major metabolite of dihydrotestosterone. The mean values for both androgens were significantly higher than in 18 normal women in the same age range. Sixteen of the 26 fibrocystic disease patients also had endometrial hyperplasia. Since the endometrial specimen was obtained in the premenstrual period, the presence of hyperplasia proved that the menstrual cycle in over two-thirds of the fibrocystic disease patients was nonovulatory.
A case of an unusual combination of a metastasing bronchus cancer, a non-metastasing cancer of prostata and an excessive high level of serum-estrogen is described. This casuistic gives rise to some more general discussion of the pathogenesis and differential diagnosis of paraneoplastic endocrinopathies.
An analysis of 235 patients with galactorrhea (5.5 per cent males) showed that 20 per cent of all patients, and 34 per cent of women with associated amenorrhea, had radiologically evident pituitary tumors; these patients had the highest serum prolactin concentrations. The largest single group (32 per cent) consisted of women with idiopathic galactorrhea without amenorrhea; prolactin was normal in 86 per cent of these cases. Five patients had the empty-sella syndrome. Prolactin response was tested in selected patients by thyrotropin-releasing hormone, chlorpromazine, L-dopa, 24-hour sampling and other means. Tests with thyrotropin-releasing hormone were most useful in identifying patients with pituitary tumors. Surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea, and amenorrhea often persisted after treatment. The ergot derivatives, bromergocryptine and lergotrile mesylate, lowered prolactin in all 18 patients with idiopathic hyperprolactinemia or pituitary tumor, stopped galactorrhea in over 50 per cent, restored menses in over 70 per cent, and allowed pregnancy in three.
Two cases of Hodgkin's disease were associated with a breast tumor after a remission of seven years. Conversely, another patient was affected by a mammary adenocarcinoma prior to the onset of an overt acute lymphoblastic leukemia in the same delay. These three observations focussed our attention upon the development of secondary neoplasias and the possible relationship between both types of disorders. In a period with extensive research on cancer etiology, it seemed interesting to discuss the role of several factors: genetic, therapeutic and/or immunological ones.
The increased frequency of meningiomas in women compared with men, and the rapidly progressive course of these tumors in pregnant patients suggest that hormones may be involved in this disease. Tumor tissue from six patients with meningiomas was analyzed for estrogen-receptor protein. Two patients had tumors with very high concentrations of this protein, approaching that found in hormonally sensitive breast carcinoma. The biochemical and possible clinical significance of these findings is discussed.
Current evidence for the involvement of diet in cancer etiology is based on indirect relationships between the consumption of selected food constituents and incidence, dietary studies, and laboratory data. The indirect evidence most often referred to is the suggested correlation between the complex of fats-meat-egg-animal protein and the risk for cancer of the colon. Such observations are, however, hampered by the fact that human diet does not consist of isolated food components. Case control studies implicate a higher intake of starchy foods in gastric cancer, a lower intake of fiber in colon cancer, and possibly coffee in renal cancer. Carcinogenic agents identified include food additives, plant toxicants, aflatoxins, polycyclic hydrocarbons, nitrosamines, and certain normal major food constituents. The experimental evidence is augmented by studies indicating an inter-relationship between dietary constituents, intestinal flora, and bile acid metabolism. A synergistic action of ingested or metabolized carcinogens and a co-carcinogenic function of certain dietary components are suggested.
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BACKGROUND: Transcriptome-wide association studies (TWAS) integrate gene expression and genome-wide association studies (GWAS) to identify disease susceptibility genes. Because gene expression varies substantially across cell types within tissues, cell type-specific prediction models may enhance the power of TWAS. METHODS: We conducted cell type-specific TWAS leveraging single-cell RNA sequencing data from the OneK1K cohort (14 immune cell types, 1.27 million cells) and GWAS summary statistics for 7 cancers (>290 000 cases in total). To improve prediction accuracy, we developed a modeling framework that incorporates shared gene expression effects across cell types. RESULTS: At a false discovery rate of 5%, we identified 106 (Bonferroni 5%: 13) previously unreported loci for breast cancer, 51 (4) loci for prostate cancer, 11 (4) loci for lung cancer, 39 (5) loci for melanoma, 9 (1) loci for ovarian cancer, and 2 (1) loci for diffuse large B-cell lymphoma, with most genes exhibiting cell type specificity. Gene set analyses confirmed joint associations of unreported genes with breast and prostate cancer risk in UK Biobank data. Additional lung tissue single-cell RNA sequencing data with 113 individuals validated 18 of 32 (56.3%) statistically significant genes for lung cancer. Across cancers, 139 statistically significant genes were shared by at least 2 cancer types and were primarily enriched in specific immune cell types. CONCLUSION: Cell type-specific TWAS improve the identification of novel cancer susceptibility loci and provide insights into the immune landscape of cancer etiology.
The development of epidemiological research on diet and cancer during the last decades is discussed. Apart from some consistent data on the protection against several cancers conferred by a diet rich in fruits and vegetables, the results provided by retrospective case-control studies on diet and cancer remain contradictory on many important issues, and primarily on the relation between diet and breast cancer. The rationale is presented for setting up large prospective cohort studies combining epidemiological and laboratory methods in order to expand the presently limited knowledge of the role of nutrition and related factors in cancer etiology. The main features of the European Prospective Investigation into Cancer and Nutrition are outlined. The study is being carried out in seven European countries and it will collect data on diet, other lifestyle and environmental factors, anthropometry as well as biological samples in a cohort of about 400,000 healthy European adults. The subjects will be followed up to investigate the incidence of and mortality from cancer in relation to epidemiological data and biochemical markers.