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PubMed2025

Genetic Analysis of Early Neoplasia in the Breast: Next-Generation Sequencing of Flat Epithelial Atypia and Associated Ductal and Lobular Lesions.

The molecular features of invasive breast cancers (IBC) have been well-characterized, but less is known about the earlier stages of neoplasia, including oncogenic drivers in early intraductal lesions. Flat epithelial atypia (FEA) is considered the earliest recognized precursor in the low-grade neoplasia pathway, but its mutational repertoire has not been studied, and drivers of the transition to morphologically more advanced lesions are unknown. Herein, we utilized next-generation sequencing to analyze 39 synchronous lesions from 13 patients, including FEA (n = 12) or predominantly FEA with early atypical ductal hyperplasia (FEA/early atypical ductal hyperplasia [ADH], n = 5) and associated ADH (n = 2), ductal carcinoma in situ (ductal carcinoma in situ [DCIS], n = 11), lobular carcinoma in situ (n = 3), and/or IBC with ductal and/or lobular differentiation (n = 6). Aside from 1 DCIS sample, all sequenced lesions in each patient were clonally related to one another. Recurrent alterations in FEA and FEA/early ADH included PIK3CA (69%), NCOR1 (31%), CBFB (31%), RUNX1 (15%), and GATA3 (23%). The mutational repertoire of FEA was similar to The Cancer Genome Atlas luminal IBC, except CBFB and NCOR1 mutations, which were more frequent in FEA and (along with PIK3CA, FOXA1, and CDKN1B) not always identified in paired morphologically advanced lesions. Compared with FEA, DCIS had more mutations and chromosomal copy number changes, including aberrations in PI-3 kinase pathway, transcription factors, chromatin remodeling genes, and TP53. CDH1 mutations identified in lobular carcinoma in situ were absent in paired FEA. Analysis of cases with ductal and lobular heterogeneity, including Rosen's triad, confirmed the shared clonality of the ductal and lobular components with features of genetic divergence. IBC of no special type were genetically similar to DCIS, and tubular carcinomas were similar to FEA. The results reveal the mutational repertoire of FEA and the genetics of early breast neoplasia, highlighting the clonal relationships of FEA to ductal and lobular carcinomas. Luminal breast cancer-associated genetic alterations are present at the earliest morphologically recognized stages of neoplasia.

Humans↗
PubMed2001

Occupation and the risk of laryngeal cancer in Turkey.

OBJECTIVES: A hospital-based case-referent study was conducted in Turkey to provide further information on occupational risk factors and laryngeal cancer. METHODS: Among 7631 cancer cases seen at an oncology treatment center between 1979 and 1984, 958 laryngeal cancer cases were identified among men. Occupational history, tobacco and alcohol use, and demographic data were obtained from patients with a standardized questionnaire. Special 7-digit standard occupational and industrial codes were created to classify the job and industrial titles of the subjects. After exclusions, 940 laryngeal cancer cases and 1519 referents were available for study. Age-, smoking- and alcohol-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. RESULTS: Excess laryngeal cancer occurred among guards (OR 1.5, 95% CI 1.1-2.1), production supervisors (OR 1.8, 95% CI 1.1-3.1), textile workers (OR 1.9, 95% CI 1.2-3.3), drivers (OR 1.7, 95% CI 1.1-2.4), construction workers (OR 1.7, 95% Cl 1.2-2.6), and workers in grain mills (OR 3.1, 95% CI: 1.3-7.6), trade unions (OR 3.6, 95% CI: 1.1-11.7) and local government services (OR 4.7, 95% CI 1.7-12.5). Supraglottic cancer was excessive among the textile workers, construction workers, and local government laborers, all with potential dust exposure. The risks of the general managers, electricians, and workers from industries such as pharmaceutical production, industrial machinery production, electric utilities, and retail services were lower than expected. CONCLUSIONS: The risk of laryngeal cancer was associated with several occupations, and supraglottic larynx cancer appears to be more common among workers in dusty occupations and industries.

Aged↗
PubMed2001

Synergistic growth inhibition of prostate cancer cells by 1 alpha,25 Dihydroxyvitamin D(3) and its 19-nor-hexafluoride analogs in combination with either sodium butyrate or trichostatin A.

Prostate cancer is a major cause of male cancer death. In vitro and in vivo data support a role for 1 alpha,25 Dihydroxyvitamin D(3) (1 alpha,25(OH)(2)D(3)) in regulating the growth and differentiation of the normal prostate gland yet prostate cancer cells appear significantly less sensitive to this action. Vitamin D(3) receptor (VDR) content or mutational status do not correlate clearly with the antiproliferative effects of 1 alpha,25(OH)(2)D(3) and therefore it is unclear why prostate cancer cell lines are significantly less sensitive to this action. We hypothesized that the antiproliferative responses of prostate cancer cells to 1 alpha,25(OH)(2)D(3) are suppressed by a process involving histone deacetylation. Sodium butyrate (NaB) and trichostatin A (TSA) are inhibitors of histone deacetylase (HDAC) activity. Low doses of NaB or TSA (300 microM and 15 nM respectively), which alone were relatively inactive, synergized with 1 alpha,25(OH)(2)D(3) in liquid and semi-solid agar to inhibit the growth of LNCaP, PC-3 and DU-145 prostate cancer cells. Still greater synergy was observed between vitamin D(3) hexafluoride analogs and either NaB or TSA. The mechanism appeared to involve neither the cyclin-dependent kinase inhibitor, p21((waf1/cip1)) nor cell cycle arrest, but rather induction of apoptosis. These data suggest that cells dysregulate the normal pro-apoptotic signals of 1 alpha,25(OH)(2)D(3) during prostate cancer development by a mechanism involving histone deacetylation. Combination therapy with potent vitamin D(3) analogs and clinically approved HDAC inhibitors may overcome this lesion and improve the treatment of both androgen-dependent and independent prostate cancer.

Antineoplastic Agents↗
PubMed1997

Alcohol consumption in relation to endometrial cancer risk.

We analyzed data from a population-based case-control study of Wisconsin women to evaluate the relationship of alcohol consumption to endometrial cancer risk. Cases (n = 739) were identified from a statewide tumor registry; controls (n = 2313) were selected randomly from driver's license lists and Medicare beneficiary files. Alcohol consumption and other factors were ascertained by telephone interview. Compared with abstainers, the multivariable relative risk for recent consumption of two or more drinks per day was 1.27 [95% confidence interval (CI) 0.78-2.07]; increasing consumption was not associated with risk of disease (P for trend, 0.82). The relative risk for early adulthood consumption of two or more drinks per day was 1.00 (95% CI, 0.58-1.73), with no suggestion of a trend (P = 0.26). Although the sample size was limited, a significant inverse association was suggested in premenopausal women consuming one drink per day or more (0.20, 95% CI 0.06-0.71). Beverage-specific consumption was not associated with risk. This study suggests that, unlike breast cancer, endometrial cancer is not positively associated with alcohol intake.

Adult↗
PubMed2006

Utilization and cost of health care services associated with primary malignant brain tumors in the United States.

OBJECTIVES: To evaluate the economic burden of primary malignant brain tumors in a commercially insured population in the United States, and to identify the primary drivers of health care resource use and cost. PATIENTS AND METHODS: A retrospective cohort analysis was performed using a 1998-2000 database containing inpatient, outpatient, and pharmacy claims for employees, their dependents, and early retirees of over 50 large US employers with wide geographic distribution. Patients were followed from first brain tumor diagnosis until death, termination of health benefits coverage, or study end. Controls without any cancer diagnosis were matched at a 3:1 ratio by demographic characteristics and length of follow-up. RESULTS: Patients with malignant brain tumors (n = 653) had significantly greater health service utilization and costs for hospitalizations, emergency room visits, outpatient office visits, laboratory tests, radiology services, and pharmacy-dispensed drugs (all P < 0.05) than did controls (n = 1959). Regression-adjusted mean monthly costs were $6364 for brain tumor patients, compared with $277 for controls (P < 0.0001). The primary cost driver was inpatient care ($4502 per month). Total costs during the study period were $49,242 for those with brain tumors and $2790 for controls (P < 0.0001). CONCLUSION: Patients with malignant brain tumors accrued health care costs that were 20 times greater than demographically matched control subjects without cancer. The costs for inpatient services were the primary drivers of total health resource use. Despite their low incidence, primary malignant brain tumors produce a substantial burden on the US health care system. There is a marked need for improved and new approaches to treatment to reduce the resource use and to offset health care costs associated with this disease.

Brain Neoplasms↗
PubMed1985

Truck driving and bladder cancer mortality in rural New England.

The relationship between truck driving and bladder cancer mortality was investigated in a case-control study in New Hampshire and Vermont. In-person interviews were conducted with the next-of-kin of 325 bladder cancer cases and 673 controls who died during 1975-79. There were 35 cases and 53 controls who had ever been employed as truck drivers [odds ratio (OR)=1.5, 95% confidence interval (CI)=0.9, 2.6]. There was a statistically significant, but inconsistent, positive association between number of years of truck driving and the OR's, rising to 2.3 (1.2,4.1) for 5 years or more of truck driving. Risk was greatest in men who began driving in the 1930's and 1940's (OR=2.6, 95% CI=1.3,5.1) and among residents of two of the most urbanized counties (OR=3.0, 95% CI=1.2,7.4). The association of bladder cancer with truck driving was unaffected by control for possible confounding factors, such as cigarette smoking and coffee drinking. It was not possible to determine whether the risks associated with truck driving were specifically due to diesel fumes. Truck drivers reporting diesel exposures had an OR=1.8 (95% CI=0.5,7.0), but those without diesel exposure still had an OR=1.5 (95% CI=0.8,2.7). Twenty-six cases and 39 controls reported exposure to diesel emissions in any occupation (OR=1.5, 95% CI=0.8,2.8), and a significant duration-response relationship was seen, rising to threefold for those employed in such jobs for 30-39 years.

Automobile Driving↗
PubMed1994

Lactation and a reduced risk of premenopausal breast cancer.

BACKGROUND: The evidence of an association of lactation with a reduction in the risk of breast cancer among women has been limited and inconsistent. The effect of lactation appears to be confined to premenopausal women with a history of long lactation, but most studies of this relation have been limited in statistical power. We conducted a multicenter, population-based, case-control study with a sample large enough for us to describe more precisely the association between lactation and the risk of breast cancer. METHODS: Patients less than 75 years old who had breast cancer were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from lists of licensed drivers if the case subjects were less than 65 years old, and from lists of Medicare beneficiaries if they were 65 through 74 years old. Information on lactation, reproductive history, and family and medical history was obtained by means of telephone interviews. After the exclusion of nulliparous women, 5878 case subjects and 8216 controls remained for analysis. RESULTS: After adjustment for parity, age at first delivery, and other risk factors for breast cancer, lactation was associated with a slight reduction in the risk of breast cancer among premenopausal women, as compared with the risk among women who were parous but had never lactated (relative risk, 0.78; 95 percent confidence interval, 0.66 to 0.91); the relative risk of breast cancer among postmenopausal women who had lactated, as compared with those who had not, was 1.04 (95 percent confidence interval, 0.95 to 1.14). With an increasing cumulative duration of lactation, there was a decreasing risk of breast cancer among premenopausal women (P for trend < 0.001) but not among postmenopausal, parous women (P for trend = 0.51). A younger age at first lactation was significantly associated with a reduction in the risk of premenopausal breast cancer (P for trend = 0.003). As compared with parous women who did not lactate, the relative risk of breast cancer among women who first lactated at less than 20 years of age and breast-fed their infants for a total of six months was 0.54 (95 percent confidence interval, 0.36 to 0.82). CONCLUSIONS: There is a reduction in the risk of breast cancer among premenopausal women who have lactated. No reduction in the risk of breast cancer occurred among postmenopausal women with a history of lactation.

Age Factors↗
PubMed2026

Clinical, Histopathological, and Molecular Characterization of Pediatric MN1::ZNF341-Associated Cancer.

A lethal round-cell malignancy with an MN1::ZNF341 fusion has recently been reported in three infants. Here, we describe four further tumors, three in newborns (including monozygotic twins), and one in an adolescent. Detailed clinical, radiological, and histopathological data differentiate these tumors from their main mimics, neuroblastoma and round-cell sarcomas. Single-cell RNA sequencing confirms the tumor to be transcriptionally distinct from neuroblastoma, instead exhibiting steroidogenic differentiation. Whole genome and targeted DNA sequencing yield no further driver events. Our work reveals a broader clinicopathological phenotype than previously appreciated and corroborates suggestions that this tumor is a distinct and aggressive childhood cancer.

Humans↗
PubMed1996

Recent oral contraceptive use and risk of breast cancer (United States)

We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States. Cases (n = 6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls (n = 9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview. After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR] = 1.1, 95 percent confidence interval [CI] = 1.0-1.2). Total duration of use also was not related to risk. There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI = 0.9-1.9). However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR = 2.0, CI = 1.1-3.9). Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index (kg/m2) less than 20.4, RR = 1.7, CI = 1.1-2.8. While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users.

Adult↗
PubMed2026

The Genomic Landscape of MYC-, MYCL-, and MYCN-Amplified Solid Tumors.

PURPOSE: MYC, MYCN, and MYCL amplifications are recurrent oncogenic events across solid tumors. Currently, no standardized selection biomarker is available to identify patients with MYC-dependent tumors. EXPERIMENTAL DESIGN: We analyzed copy-number alterations of MYC family genes and their features in more than 68,000 tumor-normal paired samples from pediatric and adult patients sequenced with MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) and annotated with FACETS (Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing). The relationship between amplification features and MYC mRNA expression levels were evaluated in more than 10,000 samples from The Cancer Genome Atlas (TCGA). RESULTS: Across MSK Cancer Center samples, MYC amplifications were most common, found in 2,949 samples compared with 310 in MYCL and 217 in MYCN. Although MYCN and MYCL amplifications were predominantly focal (<10 Mb, 79% and 93%, respectively), MYC amplifications were frequently broader (>10 Mb, 62%). Although most tumor types showed similar features between broad and focal amplifications of MYC, in select cancer types, we identified differing co-occurrence and mutual exclusivity patterns with other disease-specific drivers. Furthermore, although MYC-amplified TCGA samples showed higher mRNA expression than wild-type ones, the focality of MYC amplification was seen to have limited influence on expression levels. CONCLUSIONS: Our results suggest that MYC dependency likely depends on many factors, including, but not limited to, total copy number of the detected amplification, lineage-specific factors, concomitant presence or absence of additional oncogenic alterations, and in some cases amplification focality.

Humans↗
PubMed1990

[Advanced abdominal cancer. Treatment of complications].

Gastrointestinal obstruction and fistulas are well known complications in advanced cancer. Complications are common after surgery. Two case-histories illustrate etiology and treatment. A small syringe driver enables subcutaneous infusion. Continuous support by means of antiemetic, analgetic and anticholinergic drugs can provide sufficient control of symptoms. Patients with severe gastrointestinal obstruction can be cared for in their homes during the final weeks and months of terminal disease. Only rarely is tube-feeding or parenteral-nutrition indicated.

Adult↗
PubMed2024

SJPedPanel: A Pan-Cancer Gene Panel for Childhood Malignancies to Enhance Cancer Monitoring and Early Detection.

PURPOSE: The purpose of the study was to design a pan-cancer gene panel for childhood malignancies and validate it using clinically characterized patient samples. EXPERIMENTAL DESIGN: In addition to 5,275 coding exons, SJPedPanel also covers 297 introns for fusions/structural variations and 7,590 polymorphic sites for copy-number alterations. Capture uniformity and limit of detection are determined by targeted sequencing of cell lines using dilution experiment. We validate its coverage by in silico analysis of an established real-time clinical genomics (RTCG) cohort of 253 patients. We further validate its performance by targeted resequencing of 113 patient samples from the RTCG cohort. We demonstrate its power in analyzing low tumor burden specimens using morphologic remission and monitoring samples. RESULTS: Among the 485 pathogenic variants reported in RTCG cohort, SJPedPanel covered 86% of variants, including 82% of 90 rearrangements responsible for fusion oncoproteins. In our targeted resequencing cohort, 91% of 389 pathogenic variants are detected. The gene panel enabled us to detect &#x223c;95% of variants at allele fraction (AF) 0.5%, whereas the detection rate is &#x223c;80% at AF 0.2%. The panel detected low-frequency driver alterations from morphologic leukemia remission samples and relapse-enriched alterations from monitoring samples, demonstrating its power for cancer monitoring and early detection. CONCLUSIONS: SJPedPanel enables the cost-effective detection of clinically relevant genetic alterations including rearrangements responsible for subtype-defining fusions by targeted sequencing of &#x223c;0.15% of human genome for childhood malignancies. It will enhance the analysis of specimens with low tumor burdens for cancer monitoring and early detection.

Humans↗
PubMed1996

Cigarette smoking and breast cancer.

A priori hypotheses suggest that cigarette smoking could either increase or decrease breast cancer incidence. To clarify these competing hypotheses, we used data from a very large population-based breast cancer case-control study to investigate the impact of smoking on breast cancer risk. Breast cancer patients less than 75 years old were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire; controls were randomly selected from driver's license lists (age less than 65) or lists of Medicare beneficiaries (age 65-74). Information on reproductive history, medical history, and personal habits including cigarette smoking was obtained by telephone interview. A total of 6,888 cases and 9,529 controls were interviewed. There was virtually no relationship between current smoking and breast cancer risk (multivariate odds ratio, 1.00; 95% confidence interval, 0.92-1.09), and former smokers had a barely increased risk (odds ratio, 1.10; 95% confidence interval, 1.01-1.19). Similar results were observed among both premenopausal and postmenopausal women. There was no suggestion that heavy or long-term smoking increased or decreased risk, nor were there indications that women who began smoking at an early age were at increased risk, as has been hypothesized. The results of this large population-based study indicate that smoking does not influence the risk of breast cancer, even among heavy smokers who began smoking at an early age.

Age Factors↗
PubMed2025

Ancestry and somatic profile predict acral melanoma origin and prognosis.

Acral melanoma, which is not ultraviolet (UV)-associated, is the most common type of melanoma in several low- and middle-income countries including Mexico. Latin American samples are significantly underrepresented in global cancer genomics studies, which directly affects patients in these regions as it is known that cancer risk and incidence may be influenced by ancestry and environmental exposures. To address this, we characterise the genome and transcriptome of 123 acral melanoma tumours from 92 Mexican patients, a population notable because of its genetic admixture. Compared with other studies of melanoma, we found fewer frequent mutations in classical driver genes such as BRAF, NRAS or NF1. While most patients had predominantly Amerindian genetic ancestry, those with higher European ancestry had increased frequency of BRAF mutations and a lower median number of structural variants. The tumours with activating BRAF mutations have a transcriptional profile more similar to cutaneous non-volar melanocytes, suggesting that acral melanomas in these patients may arise from a distinct cell of origin compared to other tumours arising in these locations. KIT mutations were found in a subset of these tumours, and quadruple wild-type samples (non BRAF/NRAS/NF1/KIT) differed from mutated samples in their structural genomic profile and overall and recurrence-free survival patterns. Transcriptional profiling defined three expression clusters; these characteristics were associated with recurrence-free and overall survival. We highlight potential novel low-frequency drivers, such as PTPRJ, NF2 and RDH5. Our study enhances knowledge of this understudied disease and underscores the importance of including samples from diverse ancestries in cancer genomics studies.

Journal Article↗
PubMed1992

Cholesterol and cancer in a population of male civil service workers.

Cancer incidence and mortality were ascertained in a cohort of 1910 male participants of the Albany Cardiovascular Health Center (CVHC). The New York State Cancer Registry, vital records files, CVHC follow-up records, New York State Retirement System files, and New York State Department of Motor Vehicles driver's license files were used. Serum cholesterol measurements as well as values for other exposure variables were obtained from records of medical examinations which began in 1953-1954. The study cohort was divided into two groups, based on initial serum cholesterol measurement (less than or equal to 190 mg/100 ml and less than or equal to 190 mg/100 ml). For total cancers, both incidence and mortality were similar in these groups. For digestive cancer, both incidence and mortality were slightly lower in the less than or equal to 190 mg/100 ml group. The deficit was not statistically significant. For respiratory cancer, relative risk and rate ratio estimates were in the range of 1.4-1.7 for incidence and mortality. The excess risk in the less than or equal to 190 mg/100 ml group was of borderline statistical significance. The association was concentrated in the lowest cholesterol quintile rather than suggesting a strong dose-response relationship. The estimates were not found to be confounded by cigarette smoking, body mass index, education or age. A reduction in the crude rate ratio estimate from 1.5 to 1.2 was observed when early cases were excluded, suggesting that part of the observed excess may be due to preclinical cancer.

Adult↗
PubMed2002

Stomach cancer and occupation in Sweden: 1971-89.

OBJECTIVES: To examine the relation between gastric cancer and occupation among men and women gainfully employed in 1970 in Sweden for the period 1971-89 and, more specifically, to evaluate whether any excess of incidence of gastric cancer had also occurred among the subcohort of people reporting the same occupation in 1960 and 1970. METHODS: In both sexes and cohorts, relative risks adjusted for age, period of diagnosis, and geographical risk area were computed for occupational codes specified at one, two, or three level (occupational sector, occupational group, and occupation, respectively). Relative risks were calculated with all other occupations as reference and then, to take socioeconomic status into account, solely other occupations within the same occupational sector were used. RESULTS: Among men, occupations with increased risk included miners and quarrymen, construction and metal processing workers, supporting the possible causative role of dusty environments in stomach cancer. In men, the results also provide support for increased risks among electrical and mechanical engineers, fishermen, petrol station workers, motor vehicle drivers, butchers and meat preparers, dockers, freight handlers, launderers and dry cleaners. Furthermore, it is worth noting interesting results for women, whose occupational risks have been studied less. Excess risks were found for practical nurses, cashiers, bank employees, engineering and electronic industry workers, food industry, housekeeping and cleaning workers. Due to the many occupations studied, several significant associations may be expected by chance. CONCLUSIONS: The study is explorative but provides support for the relations suggested previously between occupational exposure to dusty environments and stomach cancer, together with some new high risk occupations which should be further studied.

Adult↗
PubMed2000

Breast feeding practices in relation to endometrial cancer risk, USA.

OBJECTIVE: Breast feeding is associated with reduced estrogen, a profile that should be associated with decreased endometrial cancer incidence. We analyzed data from a population-based case-control study of Wisconsin women to evaluate the relation between lactation and endometrial cancer risk. METHODS: Cases (n = 586) were identified from a statewide tumor registry; controls (n = 1653) were selected randomly from driver's license lists and Medicare beneficiary files. Breast feeding practices and other factors were ascertained by telephone interview. RESULTS: Compared with parous women who did not breast feed, the multivariate relative risk for women who breast fed for at least 2 weeks was 0.90 [95% confidence interval (CI) 0.72-1.13]; increasing duration was not strongly associated with risk of disease (p for trend 0.4). More recent breast feeding was associated with significantly reduced risks. The relative risk for lactation within the recent three decades was 0.58 (95% CI 0.36-0.96) and for first breast feeding at age 30 or greater was 0.50 (95% CI 0.28-0.90). There was a suggestion that risk was increased in women who used lactation suppressant hormones--usually estrogens--more recently (p = 0.1) or at a later age (p = 0.1). CONCLUSIONS: This study suggests that, like breast cancer, endometrial cancer is modestly inversely associated with lactation.

Adult↗
PubMed2001

Metabolic disorders and breast cancer risk (United States).

OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.

Aged↗