Biomedical subjects

Mark E Sherman

Publications and source records attributed to Mark E Sherman.

At least 37 records · Page 2Linked to original sources

PubMed2005

Family history as a co-factor for adenocarcinoma and squamous cell carcinoma of the uterine cervix: results from two studies conducted in Costa Rica and the United States.

Previous work suggests that cervical cancer may aggregate in families. We evaluated the association between a family history of gynecological tumors and risk of squamous cell and adenocarcinomas of the cervix in 2 studies conducted in Costa Rica and the United States. The Costa Rican study consisted of 2,073 women (85 diagnosed with CIN3 or cancer, 55 diagnosed with CIN2 and 1,933 controls) selected from a population-based study of 10,049 women. The U.S. study consisted of 570 women (124 with in situ or invasive adenocarcinomas, 139 with in situ or invasive squamous cell carcinomas of the cervix and 307 community-based controls) recruited as part of a multicentric case-control study in the eastern part of the United States. Information on family history of cervical and other cancers among first-degree relatives was ascertained via questionnaire. Information on other risk factors for cervical cancer was obtained via questionnaire. Human papillomavirus (HPV) exposure was assessed in both studies using broad spectrum HPV L1-based PCR testing of exfoliated cervicovaginal cells and in Costa Rica by additional testing of plasma collected from participants for antibodies against the L1 protein of HPV types 16, 18, 31 and 45 by ELISA. A family history of cervical cancer in a first-degree relative was associated with increased risk of squamous tumors in both studies (odds ration [OR] = 3.2 for CIN3/cancer vs. controls; 95% confidence interval [CI] = 1.1-9.4 in Costa Rica; OR = 2.6 for in situ/invasive squamous cell carcinoma cases vs. controls, 95% CI = 1.1-6.4 in the Eastern United States study). These associations were evident regardless of whether the affected relative was a mother, sister or daughter of the study participant. Furthermore, observed effects were not strongly modified by age. In Costa Rica, the effect persisted in analysis restricted to HPV-exposed individuals (OR = 3.0; 95% CI = 1.0-9.0), whereas in the Eastern United States study there was evidence of attenuation of risk in analysis of squamous carcinoma cases restricted to HPV positive women (OR = 1.4; 95% CI = 0.29-6.6). No significant association was observed between a family history of cervical cancer in a first-degree relative and adenocarcinomas (OR = 1.3; 95% CI = 0.43-3.9). History of gynecological tumors other than cervical cancer in a first-degree relative was not significantly associated with risk of disease in either study. These results are consistent with a role of host factors in the pathogenesis of squamous cell cervical cancer, although familial aggregation due to shared environmental exposures cannot be ruled out.

Adenocarcinoma↗

PubMed2005

The carcinogenicity of human papillomavirus types reflects viral evolution.

Persistent infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancers. Cervical HPV types (n > 40) also represent the most common sexually transmitted agents, and most infections clear in 1-2 years. The risks of persistence and neoplastic progression to cancer and its histologic precursor, cervical intraepithelial neoplasia grade 3 (CIN3), differ markedly by HPV type. To study type-specific HPV natural history, we conducted a 10,000-woman, population-based prospective study of HPV infections and CIN3/cancer in Guanacaste, Costa Rica. By studying large numbers of women, we wished to separate viral persistence from neoplastic progression. We observed a strong concordance of newly-revised HPV evolutionary groupings with the separate risks of persistence and progression to CIN3/cancer. HPV16 was uniquely likely both to persist and to cause neoplastic progression when it persisted, making it a remarkably powerful human carcinogen that merits separate clinical consideration. Specifically, 19.9% of HPV16-infected women were diagnosed with CIN3/cancer at enrollment or during the five-year follow-up. Other carcinogenic types, many related to HPV16, were not particularly persistent but could cause neoplastic progression, at lower rates than HPV16, if they did persist. Some low-risk types were persistent but, nevertheless, virtually never caused CIN3. Therefore, carcinogenicity is not strictly a function of persistence. Separately, we noted that the carcinogenic HPV types code for an E5 protein, whereas most low-risk types either lack a definable homologous E5 ORF and/or a translation start codon for E5. These results present several clear clues and research directions in our ongoing efforts to understand HPV carcinogenesis.

Cocarcinogenesis↗

PubMed2005

A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica.

BACKGROUND: Cross-sectional human papillomavirus (HPV) DNA prevalence peaks at young ages, reflecting sexual acquisition and typically rapid clearance. In some populations, HPV prevalence demonstrates a second peak in older women. Longitudinal data may help to explain this second peak. METHODS: We followed a population-based cohort of 7237 women in Guanacaste, Costa Rica, in which we had previously observed a second peak in the baseline HPV prevalence in older women. We tested for >40 HPV types by polymerase chain reaction. We analyzed age-specific patterns of acquisition and persistence 5-7 years after enrollment for individual HPV types. RESULTS: At enrollment and follow-up, cross-sectional data revealed U-shaped age-specific HPV prevalence curves for virtually every type, with higher prevalences in the younger and older women than in the middle-aged women. Prospectively, acquisition of types decreased significantly as women aged (PTrend<.05, for both), with the highest peak in young women and a secondary minor peak in older women. Type-specific persistence of HPV increased with age (PTrend<.0001). Overall, HPV acquisition predominated at younger ages, whereas persistent infections gradually became more prominent with age (PTrend<.0001). CONCLUSIONS: Newly apparent infections decreased, whereas persistence increased, with age; this latter tendency supports the utility of HPV screening in older women.

Adult↗

PubMed2005

Epidemiologic profile of type-specific human papillomavirus infection and cervical neoplasia in Guanacaste, Costa Rica.

BACKGROUND: Detailed epidemiologic studies of cervical type-specific human papillomavirus (HPV) infection in large populations are scarce. METHODS: We recruited a population-based cohort in Guanacaste, Costa Rica. Participants were interviewed, screened for cervical neoplasia, and tested for >40 HPV types by use of MY09/11 L1 consensus primer polymerase chain reaction. We estimated the risk factors for infection and the associations between type-specific HPV infections and cervical intraepithelial neoplasia (CIN) and cancer in 8514 sexually active women who had not undergone a hysterectomy. RESULTS: The overall HPV prevalence was 26.5%. The most common type was HPV-16 (3.6% of the population). HPV prevalence showed a U-shaped age-specific curve. Sexual behaviors were the main determinants of oncogenic and nononcogenic infections; age at first sexual intercourse was not independently associated with infection. Barrier contraceptive use was somewhat protective against infection. Oncogenic infections were strongly associated with risk of all grades of CIN and of cancer. Types 16, 18, and 58 were the most common in women diagnosed with CIN3 and cancer. Except for those that included HPV-16, multiple-type infections were associated with an increased risk (compared with that for single-type infections) of all grades of CIN and of cancer. CONCLUSIONS: We confirmed the bimodal age pattern of HPV infection in Guanacaste and the sexually transmitted nature of both oncogenic and nononcogenic HPV types.

Adult↗

PubMed2005

Mortality trends for cervical squamous and adenocarcinoma in the United States. Relation to incidence and survival.

BACKGROUND: In the United States, detection of squamous carcinoma in situ (CIS) by screening has led to reduced rates for invasive squamous carcinoma and lower mortality. Adenocarcinoma in situ (AIS) rates also have increased, but invasive cervical adenocarcinoma rates have not declined similarly. To make inferences about the effectiveness of screening, the authors assessed mortality trends for squamous and adenocarcinoma in relation to incidence of these tumors, incidence of their precursors and survival. METHODS: Using data from the Surveillance, Epidemiology, and End Results program (SEER), the authors tabulated incidence per 10(5) woman-years for invasive carcinomas (1976-2000) and for CIS and AIS (1976-1995) by age (< 50 years, > or = 50 years) and race (whites, blacks). Cumulative relative survival rates were tabulated for 1976-1995 and mortality rates were estimated for 1986-2000. RESULTS: Among all groups, CIS rates approximately doubled whereas rates for invasive squamous carcinoma declined. Among younger whites, mortality declined from 1.12 to 0.93, and for older whites, mortality decreased from 5.02 to 3.82. Among younger blacks, mortality for squamous carcinoma decreased from 2.69 to 1.96. Among older blacks, the mortality rates declined from 14.88 to 9.15. Although AIS rates have increased dramatically among whites (all ages) and younger blacks, adenocarcinoma incidence and mortality rates have not changed greatly. Survival for patients did not change greatly within these age-race groups. CONCLUSIONS: The authors concluded that increases in CIS seemed disproportionately large compared with improvements in mortality rates for squamous carcinoma. Despite increased reporting of AIS, declines in mortality for cervical adenocarcinoma have not been demonstrated conclusively. However, future analyses are required to evaluate these trends more completely.

Adenocarcinoma↗

PubMed2005

Towards improved biomarker studies of cervical neoplasia: effects of precolposcopic procedures on gene expression patterns.

Among tumor sites, cervical cancer offers an ideal model for investigating differences in gene expression associated with transitions from normal to precancer and invasion to cancer. To evaluate the validity of assessing gene expression in cervical tissues acquired in a clinical setting, we investigated whether standard procedures, namely the application of acetic acid and/or Lugol's iodine, employed for the visualization of colposcopically directed biopsies, altered patterns in oligonucleotide (oligo) arrays. We compared microarray profiles from six women, each with three adjacent tissue samples removed from benign hysterectomy specimens and treated as follows: immediately frozen, acetic acid application only, acetic acid, and Lugol's iodine. Of the 22,464 original spots on the microarray, 4,850 spots were expressed at detectable levels for further evaluation upon data normalization and filtration. For each spot, the difference between topical applications was computed, and P values were calculated using a bivariate T2 test. Upon adjustment for multiple comparisons using both the Holm's and Hochberg's procedures as well as the False Discovery Rate (Benjamini-Hochberg and Benjamini-Yeuketili [BY]), we failed to identify genes differentially expressed and conclude that standard precolposcopic procedures do not substantially affect the overall gene expression patterns in the normal cervix.

Artifacts↗

PubMed2005

Semiquantitative human papillomavirus type 16 viral load and the prospective risk of cervical precancer and cancer.

We examined whether higher human papillomavirus type 16 (HPV16) viral load predicted risk of cervical intraepithelial neoplasia 3 (CIN3) or cancer (together termed > or =CIN3) within a cohort of 20,810 women followed for 10 years with cytologic screening. Semiquantitative viral load for HPV16 was measured on baseline cervicovaginal specimens using a type-specific hybridization probe test with signal amplification. An increased risk of > or =CIN3 associated with higher HPV16 viral load was found only among cytologically negative women in early follow-up, suggesting that these cases were related to the detection of prevalent lesions missed at baseline. Women with higher HPV16 viral load were more likely to undergo ablative treatment during follow-up than those with lower viral load (P(trend) = 0.008), possibly diminishing any additional risk for > or =CIN3 attributable to higher HPV16 viral loads.

Adolescent↗

PubMed2005

Serum concentrations of estrogens, sex hormone binding globulin, and androgens and risk of breast hyperplasia in postmenopausal women.

OBJECTIVE: We sought to determine whether serum concentrations of estrogens, androgens, and sex hormone binding globulin in postmenopausal women were related to the presence of mammary hyperplasia, an established breast cancer risk factor. METHODS: Study participants provided serum before breast biopsy or mastectomy in three hospitals in Grand Rapids, Michigan, between 1977 and 1987. A total of 179 subjects with breast hyperplasia were compared with 152 subjects with nonproliferative breast changes that are not associated with increased breast cancer risk. RESULTS: The odds ratios (OR) associated with the three upper quartiles of estradiol in comparison with the lowest quartile were 2.2 [95% confidence interval (95% CI) 1.1-4.6], 2.5 (95% CI, 1.1-5.3), and 4.1 (95% CI, 2.0-8.5; Ptrend = 0.007). The corresponding ORs for bioavailable estradiol, estrone, and estrone sulfate were of generally similar magnitude (Ptrend = 0.003 for bioavailable estradiol, 0.0004 for estrone, and 0.0009 for estrone sulfate). Relative to women concurrently in the lowest tertile for serum estradiol, estrone, and estrone sulfate, women concurrently in the highest tertile for all three hormones had an OR of 5.8 (95% CI, 2.2-15.2). Serum concentrations of sex hormone binding globulin, testosterone, dehydroepiandrosterone, androstenedione, and androstenediol were not associated with risk of hyperplasia. CONCLUSIONS: Serum concentrations of estrogens, but not of androgens or sex hormone binding globulin, were strongly and significantly associated with risk of breast hyperplasia in postmenopausal women, suggesting that estrogens are important early in the pathologic process towards breast cancer.

Androgens↗

PubMed2005

Endometrial carcinoma risks among menopausal estrogen plus progestin and unopposed estrogen users in a cohort of postmenopausal women.

BACKGROUND: Because unopposed estrogen substantially increases endometrial carcinoma risk, estrogen plus progestin is one menopausal hormone therapy formulation for women who have not had a hysterectomy. However, endometrial carcinoma risks among estrogen plus progestin users and among former unopposed estrogen users are not firmly established. METHODS: We evaluated endometrial carcinoma risks associated with estrogen plus progestin and unopposed estrogen therapies in 30,379 postmenopausal Breast Cancer Detection Demonstration Project follow-up study participants. We ascertained hormone therapy use and other risk factors during telephone interviews and mailed questionnaires between 1979 and 1998. We identified 541 endometrial carcinomas via self-report, medical records, the National Death Index, and state cancer registries. Poisson regression generated time-dependent rate ratios (RR) and 95% confidence intervals (95% CI). RESULTS: Endometrial carcinoma was significantly associated with estrogen plus progestin only use (n = 68 cancers; RR, 2.6; 95% CI, 1.9-3.5), including both sequential (progestin <15 days per cycle; n = 32 cancers; RR, 3.0; 95% CI, 2.0-4.6) and continuous (progestin at least 15 days per cycle; n = 15 cancers; RR, 2.3; 95% CI, 1.3-4.0) regimens. The RR increased by 0.38 (95% CI, 0.20-0.64) per year of estrogen plus progestin use, and RRs increased with increasing duration of use for both regimens. The strong association with unopposed estrogen use declined after cessation but remained significantly elevated > or =10 years after last use (RR, 1.5; 95% CI, 1.0-2.1). CONCLUSIONS: Both estrogen plus progestin regimens significantly increased endometrial carcinoma risk in this study. Risks among unopposed estrogen users remained elevated long after last use. The prospect that all estrogen plus progestin regimens increase endometrial carcinoma risk deserves continued research.

Aged↗

PubMed2005

Relationship of benign gynecologic diseases to subsequent risk of ovarian and uterine tumors.

OBJECTIVE: Although endometriosis and uterine leiomyomas are common conditions, the extent to which either is associated with certain types of malignancies remains uncertain. METHODS: Using record linkage techniques, we assessed the relationships between hospital and outpatient admissions for endometriosis or leiomyomas and the development of ovarian and uterine cancers in Denmark between 1978 and 1998. Based on a population-based cohort exceeding 99,000 women, including 2,491 ovarian cancers, 860 borderline ovarian tumors, and 1,398 uterine cancers, we derived relative risks (RR) and 95% confidence intervals (95% CI) associated with overall and histology-specific tumor risks after adjustment for calendar time and reproductive characteristics. RESULTS: Endometriosis seemed to predispose to the development of ovarian cancer, with the association restricted to endometrioid or clear cell malignancies. Five or more years after the diagnosis of endometriosis, the RRs (95% CIs) were 2.53 (1.19-5.38) for endometrioid (7 exposed cases) and 3.37 (1.24-9.14) for clear cell (4 exposed cases) malignancies. Uterine leiomyomas were associated with increases in the risk of uterine malignancies, particularly sarcomas, where the RRs (95% CIs) were 20.80 (11.32-38.22) for women with 1 to 4 years of follow-up (11 exposed cases) and 5.70 (2.27-14.32) for those with more extended follow-up (5 exposed cases). CONCLUSION: In combination with clinical, pathologic, and molecular data, our results support that some endometriotic lesions may predispose to clear cell and endometrioid ovarian cancers. Uterine leiomyomas also showed a strong connection with subsequent uterine sarcomas, although it was difficult to decipher whether this reflected detection bias, shared risk factors, or an etiologic relationship.

Adult↗

PubMed2004

Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers.

Cytochromes P450 1A1 and 1B1 are known to bioactivate procarcinogens such as polycyclic aromatic hydrocarbons (PAHs) found in cigarette smoke and are inducible via an Ah receptor-mediated mechanism. The aim of this study was to examine the levels of expression of CYP1A1 and CYP1B1 in samples of lung from smokers (n = 18), non-smokers (n = 7), and ex-smokers (n = 7). Using immunoglobulin preparations of highly specific polyclonal antibodies and immunoblot analysis of microsomes from lung tissues, we determined the specific content for CYP1A1 and CYP1B1. For CYP1A1, we found median expression levels of 15.5 pmol/mg microsomal protein in smokers, 6.0 pmol/mg microsomal protein in non-smokers, and 19.0 pmol/mg microsomal protein in ex-smokers. The difference in median expression levels of smokers and ex-smokers compared to non-smokers was statistically significant. For CYP1B1, we found median expression levels of 1.8 pmol/mg microsomal protein in smokers, 1.0 pmol/mg microsomal protein in non-smokers, and 4.4 pmol/mg microsomal protein in ex-smokers. The difference in median expression levels between ex-smokers and non-smokers was statistically significant. These results suggest that levels of expression of CYP1A1 and CYP1B1 protein in lung tissues from smokers and ex-smokers are quantitatively greater than in non-smokers. By immunohistochemical analysis, we demonstrated the expression of CYP1A1 and CYP1B1 in normal human alveolar type I and II cells, ciliated columnar epithelial cells lining bronchoalveolar airways, and alveolar macrophages. These results confirm that CYP1A1 is expressed in normal human lung, appears to be induced in smokers, and show interindividual variation; the similar characteristics of CYP1B1 are demonstrated.

Adolescent↗

PubMed2004

A population-based study of vaginal human papillomavirus infection in hysterectomized women.

We compared point prevalences and determinants of human papillomavirus (HPV) DNA detection by testing enrollment vaginal specimens from hysterectomized women (n=569) and enrollment cervical specimens from nonhysterectomized women (n=6098) >or=30 years old, using MY09/MY11 L1 consensus-primer polymerase chain reaction. The subjects were participating in a population-based cohort study (n=10,049) in Guanacaste, Costa Rica, that was initiated in 1993. Non-cancer-associated HPV types, especially types 61, 71, and 72, were detected more frequently in the vaginal specimens from hysterectomized women (23.7% [95% confidence interval [CI], 20.3%-27.4%]) than in the cervical specimens from nonhysterectomized women (16.7% [95% CI, 15.7%-17.6%]) (P=.0001). There was no difference between the prevalences of cancer-associated HPV types in hysterectomized women and those in nonhysterectomized women; in both groups, the prevalence of HPV DNA was greater in women with multiple lifetime sex partners. We infer from our data that the cervical transformation zone may not be needed for cancer-associated HPV infection but may be uniquely susceptible to HPV-induced carcinogenesis; we also infer that specific phylogenetic groups of HPV (i.e., A3/A4/A15) may have a predilection for vaginal epithelium.

Adult↗

PubMed2004

Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976-2000.

BACKGROUND: Although cervical carcinoma incidence and mortality rates have declined in the U.S. greatly since the introduction of the Papanicolaou smear, this decline has not been uniform for all histologic subtypes. Therefore, the authors assessed the differential incidence rates of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the cervix by race and disease stage for the past 25 years. METHODS: Data from nine population-based cancer registries participating in the U.S. Surveillance, Epidemiology, and End Results (SEER) Program were used to compute incidence rates for cervical carcinoma diagnosed during 1976-2000 by histologic subtype (SCC and AC), race (black and white), age, and disease stage (in situ, localized, regional, or distant). RESULTS: In black women and white women, the overall incidence of invasive SCC declined over time, and the majority of tumors that are detected currently are in situ and localized carcinomas in young women. The incidence of in situ SCC increased sharply in the early 1990s. AC in situ (AIS) incidence rates increased, especially among young women. In black women, invasive AC incidence rose linearly with age. CONCLUSIONS: Changes in screening, endocervical sampling, nomenclature, and improvements in treatment likely explain the increased in situ cervical SCC incidence in white women and black women. Increasing AIS incidence over the past 20 years in white women has not yet translated into a decrease in invasive AC incidence. Etiologic factors may explain the rising invasive cervical AC incidence in young white women; rising cervical AC incidence with age in black women may reflect either lack of effective screening or a differential disease etiology.

Adenocarcinoma↗

PubMed2004

Survival among women with borderline ovarian tumors and ovarian carcinoma: a population-based analysis.

BACKGROUND: Serous and mucinous ovarian tumors of low malignant potential (LMP-S and LMP-M, respectively) are noninvasive tumors that portend excellent survival when confined to the ovary. Comparison of the survival for women with LMP tumors staged as distant with women who have carcinoma may have important implications for diagnostic terminology and clinical management. METHODS: The authors compared relative survival rates among patients diagnosed with ovarian tumors during the period 1988-1999 (with follow-up through 2000) by histologic type, disease stage, tumor grade (for carcinomas), and patient age, using data from the Surveillance, Epidemiology, and End Results Program. RESULTS: The overall relative survival rate at 10 years (+/- 1.96 standard errors) was 96.9% +/- 2.3% for women with LMP-S tumors, 30.4% +/- 1.7% for women with serous carcinoma (CA-S); 94.0% +/- 3.1% for women with LMP-M tumors, and 64.7% +/- 3.4% for women with mucinous carcinoma (CA-M). The survival rate at 10 years for women with distant-stage LMP-S tumors was 89.9% +/- 5.3%, compared with 96.1% +/- 8.6% for women with well differentiated, localized CA-S. The survival rate for women with distant-stage LMP-M tumors at 5 years was 85.5% +/- 9.0%, compared with 95.5% +/- 3.4% for women with well differentiated, localized CA-M (data for 10 years were limited). Mucinous ovarian neoplasms were associated with an excess of second malignancies of the digestive tract. CONCLUSIONS: Relative survival among women with distant-stage LMP tumors was not 100% and resembled the survival of women who had carcinoma exhibiting favorable prognostic features (localized stage). Future studies of women with high-stage LMP tumors are required to clarify the pathogenesis of extraovarian lesions and their implications for management and prognosis.

Adenocarcinoma, Mucinous↗

PubMed2004

Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal women.

Experimental evidence suggests that insulin and insulin-related growth factors may play a role in breast pathology through their mitogenic and anti-apoptotic effects on breast cells. Our objective was to assess the relationship between serum concentrations of insulin-like growth factor-I (IGF-I), its major binding protein (IGFBP-3), the ratio IGF-I:IGFBP-3, c-peptide (a marker of insulin secretion) and the ratio c-peptide:fructosamine (a marker of insulin resistance) and the risk of epithelial hyperplasia (an established breast cancer risk factor) and localized breast cancer among postmenopausal women. Study subjects were patients who provided serum before breast biopsy or mastectomy in 3 hospitals in Grand Rapids, MI between 1977 and 1987. Two case groups, 186 subjects with epithelial hyperplasia of the breast and 185 subjects with localized breast cancer, were compared to 159 subjects with nonproliferative breast changes that have not been associated with increased breast cancer risk. Serum concentrations of IGF-I, IGFBP-3 and the ratio IGF-I:IGFBP-3 were not related to risk of either hyperplasia or breast cancer. For women in the highest quartile of c-peptide or of c-peptide:fructosamine compared to those in the lowest quartile, the odds ratios (ORs) for hyperplasia were 3.0 (95% confidence interval [CI] 1.4-6.5) and 3.3 (95% CI 1.5-7.3), respectively (p trend = 0.02 and 0.02, respectively). The corresponding ORs for breast cancer were 1.5 (95% CI 0.7-3.0) and 1.6 (95% CI 0.8-3.2), respectively (p trend = 0.35 and 0.25, respectively). Our results suggest that insulin and insulin resistance may play a role in breast pathology in postmenopausal women.

Adult↗

PubMed2004

Medication use and risk of ovarian carcinoma: a prospective study.

Inflammation and gonadotropins are hypothesized to influence ovarian carcinogenesis. In a prospective study, we evaluated ovarian cancer risk associated with self-reported use of medications that influence inflammation or gonadotropin levels. The Breast Cancer Detection Demonstration Project Follow-Up Study enrolled 61,431 women in 1979 and used telephone interviews and 3 mailed questionnaires through 1998 to update risk factor information and identify incident ovarian cancers. The 1992-95 questionnaire ascertained medication use, including duration and frequency of use for aspirin, acetaminophen, other nonsteroidal anti-inflammatory drugs (NSAIDs), tranquilizers and histamine-receptor antagonists. A Poisson regression analysis generated rate ratios (RRs) and 95% confidence intervals (CIs) for the 31,364 women who were at risk of ovarian cancer and responded to the questionnaire that queried regular medication use. One hundred sixteen women developed ovarian cancer during follow-up. None of the anti-inflammatory medications was associated with ovarian cancer, but the RR for more than 1 aspirin per day for 1 year or longer was 0.56 (95% CI 0.20-1.5) and the RR for more than 5 years of regular "other NSAID" use was 2.0 (95% CI 0.95-4.2). Regular tranquilizer use was not associated with ovarian cancer, but histamine-receptor antagonists used regularly for more than 5 years (RR = 3.6, 95% CI 1.4-9.1) or more than once daily (RR = 3.1, 95% CI 1.5-6.5) appeared to increase risk. In our study, neither anti-inflammatory medications nor anti-psychotic medications were associated with ovarian cancer. Potential associations with histamine-receptor antagonists may warrant further study.

Acetaminophen↗

PubMed2004

Risk of malignant mixed mullerian tumors after tamoxifen therapy for breast cancer.

Recent studies have indicated that the tamoxifen-related risk of uterine corpus cancer may be especially high for some uncommon cell types, although the magnitude of risk has not been quantified. We evaluated data from 39 451 breast cancer patients diagnosed from 1980 through 2000 who were initially treated with tamoxifen and found that the overall risk of subsequent uterine corpus cancer was increased more than twofold (observed-to-expected ratio [O/E] = 2.17, 95% confidence interval [CI] = 1.95 to 2.41) relative to the general SEER population. The relative risk was substantially higher for malignant mixed mullerian tumors (MMMTs) (O/E = 4.62, O = 34, 95% CI = 3.20 to 6.46) than for endometrial adenocarcinomas (O/E = 2.07, O = 306, 95% CI = 1.85 to 2.32), although the excess absolute risk was smaller-an additional 1.4 versus 8.4 cancers per 10 000 women per year, respectively. Among those who survived for 5 years or longer, there was an eightfold relative risk for MMMTs and a 2.3-fold risk for endometrial adenocarcinomas, with patients developing MMMTs having a worse prognosis. These findings indicate that tamoxifen may have delayed effects, such as the increased risk of MMMTs, rare but aggressive tumors of unclear pathogenesis.

Adenocarcinoma↗

PubMed2004

Borderline ovarian tumors: diverse contemporary viewpoints on terminology and diagnostic criteria with illustrative images.

The National Cancer Institute sponsored a Borderline Ovarian Tumor Workshop held in August 2003 in Bethesda, MD. This report was developed from discussions at the Workshop. The participants acknowledged several areas of disagreement on basic terminology issues and agreed that a glossary with example images would help clarify many commonly misunderstood issues. This report defines terminology used in the pathological description of borderline tumors and their variants, and illustrates examples of each of the most common entities. It also addresses controversial aspects of the definitions and issues involving specimen handling and reporting. For those issues where there is disagreement, the terminology and diagnostic approaches reflecting the differing views are presented.

Cystadenocarcinoma↗