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Search Results: 1 - 10 of 169036 matches for " Kathleen E Malone "
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Case-Control Study of Fetal Microchimerism and Breast Cancer
Vijayakrishna K. Gadi, Kathleen E. Malone, Katherine A. Guthrie, Peggy L. Porter, J. Lee Nelson
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001706
Abstract: Background Prior pregnancy is known to protect against development of breast cancer. Recent studies have demonstrated that pregnancy has the capacity to establish small numbers of immunologically active fetal-derived cells in the mother, a phenomenon known as fetal microchimerism (FMc). We asked whether presence of FMc, routinely acquired during pregnancy, is a protective factor for breast cancer. Methodology/Principal Findings DNA extracts from peripheral blood specimens were obtained from a population-based case-control study of risk factors for breast cancer in women 21 to 45 years old. Specimens were tested with quantitative PCR for presence and concentrations of male DNA presumed to derive from prior pregnancies with a male fetus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with consideration of multiple established reproductive and environmental risk factors for breast cancer. FMc results were generated on 99 parous women, 54 with primary invasive breast cancer and 45 general population controls. FMc prevalence was 56% (25/45) and 26% (14/54) in controls and cases, respectively. Women harboring FMc were less likely to have had breast cancer (OR = 0.29, 95% CI 0.11–0.83; p = 0.02, adjusting for age, number of children, birth of a son, history of miscarriage, and total DNA tested). In addition, FMc concentrations were higher in controls versus cases (p = 0.01). Median concentrations were 2 (0–78) and 0 (0–374) fetal genomes/106 maternal genomes in controls and cases, respectively. Conclusions Results suggest that the enigma of why some parous women are not afforded protection from breast cancer by pregnancy might in part be explained by differences in FMc. Mechanistic studies of FMc-derived protection against breast cancer are warranted.
Frequency of CHEK2 mutations in a population based, case–control study of breast cancer in young women
Danielle M Friedrichsen, Kathleen E Malone, David R Doody, Janet R Daling, Elaine A Ostrander
Breast Cancer Research , 2004, DOI: 10.1186/bcr933
Abstract: We report here on the frequency of three CHEK2 variants that alter protein function – 1100delC, R145W, and I175T – in 506 cases and 459 controls from a population based, case–control study of breast cancer conducted in young women from western Washington.There was a suggestive enrichment in the 1100delC variant in the cases (1.2%) as compared with the controls (0.4%), but this was based on small numbers of carriers and the differences were not statistically significant. The 1100delC variant was more frequent in cases with a first-degree family history of breast cancer (4.3%; P = 0.02) and slightly enriched in cases with a family history of ovarian cancer (4.4%; P = 0.09).The CHEK2 variants are rare in the western Washington population and, based on accumulated evidence across studies, are unlikely to be major breast cancer susceptibility genes. Thus, screening for the 1100delC variant may have limited usefulness in breast cancer prevention programs in the USA.Cell-cycle checkpoint kinase (CHEK)2 has been shown to play a role in cell cycle regulation, apoptosis, and DNA repair, at least in part through phosphorylation of p53 and BRCA1 in response to DNA damage [1,2]. Several studies have reported associations of germline mutations in CHEK2, especially the 1100delC mutation, with increased susceptibility to breast and prostate cancer [3-8]. Although CHEK2 germline variants other than 1100delC have been associated with prostate cancer risk, these have not yet been shown to be enriched in breast cancer cases [3,4,9,10].The association between the CHEK2 1100delC variant and risk for breast cancer was initially reported by the CHEK2 Breast Cancer Consortium [5]. They found that the frequency of the variant was greater among breast cancer patients with a positive family history of breast cancer who do not carry germline mutations in the BRCA1 or BRCA2 genes, and in families with male breast cancer, as compared with healthy control individuals from the UK, The Netherlands,
Vitamin D receptor polymorphisms and breast cancer risk in a large population-based case-control study of Caucasian and African-American women
Britton Trabert, Kathleen E Malone, Janet R Daling, David R Doody, Leslie Bernstein, Giske Ursin, Polly A Marchbanks, Brian L Strom, Mariela C Humphrey, Elaine A Ostrander
Breast Cancer Research , 2007, DOI: 10.1186/bcr1833
Abstract: We examined the association between polymorphisms in the 3' end of the VDR gene, specifically BsmI and Poly(A), and breast cancer risk within a large, population-based, case-control study of breast cancer. Cases (n = 1,631) were Caucasian and African-American women, aged 35 to 64 years, who were diagnosed with incident, invasive breast cancer between July 1994 and April 1998. Control individuals (n = 1,435) were women without breast cancer ascertained through random digit dialing.Accounting for age, study site, and sampling weights, we observed a significantly increased risk for breast cancer among Caucasian, postmenopausal carriers of the bb genotype of BsmI (odds ratio = 1.53, 95% confidence interval = 1.04 to 2.27). However, no associations with the bb genotype were observed in African-American women. Overall, there were no significant associations between the Poly(A) genotype and breast cancer risk in either racial group. Smoking status (ever/never) modified the association between both the BsmI and Poly(A) genotypes and breast cancer risk. The respective associations between these genotypes and breast cancer risk did not significantly vary by oral contraceptive use, hormone replacement therapy, or body mass index.Our results provide additional support for an increased risk for breast cancer in postmenopausal Caucasian women with the BsmI bb genotype and shed light on possible differential effects by menopausal status and race.Vitamin D is a key player in cell proliferation, differentiation, and apoptosis in normal and malignant breast cells [1,2]. Indeed, the active form of vitamin D is hypothesized to have antiproliferative effects in many types of cells, including breast cancer cells [3-6]. The observation of a reduced risk for breast cancer among women with high vitamin D status lends support to this hypothesis [3,4].Vitamin D has also been established as a determinant of bone density and, furthermore, higher bone density has been shown to be associated with
THE HUNTER OF MAN
E.M. Malone
Scientia Militaria : South African Journal of Military Studies , 2012, DOI: 10.5787/13-1-593
Abstract: The origins of sniping - the ability to kill one's enemy at a range far exceeding that of ordinary military rifles - may be traced at least as far back as 1755, in which year the British Government, licking their wounds after an inglorious defeat on the banks of the Ohio River by a combined French and Red Indian force, raised from among the American settlers a unique corps of trained marksmen, whose arms, dress and mobility approximated those of their enemies. This corps d'elite, whose birthday is given as Christmas Day 1755, was orignally named the 2nd Regiment, the title being subsequently altered to the 60th 'Royal Americans'.
Conveying misinformation: Top-ranked Japanese books on tobacco
Yuko Kanamori, Ruth E Malone
Tobacco Induced Diseases , 2011, DOI: 10.1186/1617-9625-9-3
Abstract: We searched Amazon.com Japan using the term "Tobacco", identifying the top 12 books by "relevance" and "bestselling." We eliminated duplicates and books not concerned with tobacco use and classified the remaining books as pro-smoking, anti-smoking, or neutral. We reviewed the pro-smoking books, published 2004-2009, and analyzed examples of misinformation by theme.Pro-smoking popular books conveyed five types of misinformation: doubt about science; suggestions that smoking increased health, longevity, virility, etc.; trivializing tobacco's effects; attacking public health advocates/authorities; and linking tobacco use with authenticity, history, or civil rights. At least one book was authored by a former Japan Tobacco employee; another used a popular Japan Tobacco advertising phrase.Creating doubt and confusion about tobacco serves tobacco industry interests and re-creates a strategy developed by US tobacco interests more than 40 years ago. Japanese readers may be misled by texts such as those reviewed. Tobacco control and public health advocates in Japan and globally should expose and counter such misinformation. "Naming and shaming" may be effective.Since it is established that smoking tobacco causes disease [1,2], and the landmark Japanese study showing that secondhand smoke (SHS) causes disease in nonsmokers was published almost 30 years ago [3], it is surprising that tobacco use in Japan remains so widespread that the country has been called a smokers' paradise [4]. Although nationally, smoking rates have continued dropping [5], 39.4% of Japanese men and 11.0% of Japanese women still smoke [5], and 24% of health professionals are smokers, compared with 4% overall among U.S. health professionals [6]. Tobacco control efforts in Japan lag many other countries, possibly because the Japanese government is the majority owner of Japan Tobacco, Inc. (JT) [7]. Given an absence until recently of effective central government action, it is unclear why smoking has dropped, b
Study design: Evaluating gene–environment interactions in the etiology of breast cancer – the WECARE study
Jonine L Bernstein, Bryan Langholz, Robert W Haile, Leslie Bernstein, Duncan C Thomas, Marilyn Stovall, Kathleen E Malone, Charles F Lynch, J?rgen H Olsen, Hoda Anton-Culver, Roy E Shore, John D Boice, Gertrud S Berkowitz, Richard A Gatti, Susan L Teitelbaum, Susan A Smith, Barry S Rosenstein, Anne-Lise B?rresen-Dale, Patrick Concannon, W Douglas Thompson
Breast Cancer Research , 2004, DOI: 10.1186/bcr771
Abstract: To examine the joint roles of radiation exposure and genetic susceptibility in the etiology of breast cancer, we designed a case-control study nested within five population-based cancer registries. We hypothesized that a woman carrying a mutant allele in one of these genes is more susceptible to radiation-induced breast cancer than is a non-carrier. In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer on date and age at diagnosis of the first breast cancer, race, and registry region, and counter-matched on radiation therapy. Each triplet comprised two women who received radiation therapy and one woman who did not. Radiation absorbed dose to the contralateral breast after initial treatment was estimated with a comprehensive dose reconstruction approach that included experimental measurements in anthropomorphic and water phantoms applying patient treatment parameters. Blood samples were collected from all participants for genetic analyses.Our study design improves the potential for detecting gene–environment interactions for diseases when both gene mutations and the environmental exposures of interest are rare in the general population. This is particularly applicable to the study of bilateral breast cancer because both radiation dose and genetic susceptibility have important etiologic roles, possibly by interactive mechanisms. By using counter-matching, we optimized the informativeness of the collected dosimetry data by increasing the variability of radiation dose within the case–control sets and enhanced our ability to detect radiation–genotype interactions.The WECARE (for Women's Environmental Cancer and Radiation Epidemiology) Study is a multi-center, population-based case-control study of breast cancer designed to examine the interaction of gene carrier status and radiation exposure in the etiology of breast cancer. We are currently focusing on three major breast cancer suscepti
Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study
Sharon N Teraoka, Jonine L Bernstein, Anne S Reiner, Robert W Haile, Leslie Bernstein, Charles F Lynch, Kathleen E Malone, Marilyn Stovall, Marinela Capanu, Xiaolin Liang, Susan A Smith, Josyf Mychaleckyj, Xuanlin Hou, Lene Mellemkjaer, John D Boice, Ashley Siniard, David Duggan, Duncan C Thomas, The WECARE Study Collaborative Group, and Patrick Concannon
Breast Cancer Research , 2011, DOI: 10.1186/bcr3057
Abstract: We genotyped 21 SNPs in 708 women with contralateral breast cancer and 1394 women with unilateral breast cancer who serve as the cases and controls in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study. Records of treatment and ER status were available for most of WECARE Study participants. Associations of SNP genotypes and risk for contralateral breast cancer were calculated with multivariable adjusted conditional logistic regression methods.Multiple SNPs in the FGFR2 locus were significantly associated with contralateral breast cancer, including rs1219648 (per allele rate ratio (RR) = 1.25, 95%CI = 1.08-1.45). Statistically significant associations with contralateral breast cancer were also observed at rs7313833, near the PTHLH gene (per allele RR = 1.26, 95%CI = 1.08-1.47), rs13387042 (2q35) (per allele RR = 1.19, 95%CI = 1.02-1.37), rs13281615 (8q24) (per allele RR = 1.21, 95%CI = 1.04-1.40), and rs11235127 near TMEM135 (per allele RR = 1.26, 95%CI = 1.04-1.53). The A allele of rs13387042 (2q35) was significantly associated with contralateral breast cancer in ER negative first tumors while the A allele of rs11235127 (near TMEM135) was significantly associated with contralateral breast cancer in ER positive first tumors. Although some SNP genotypes appeared to modify contralateral breast cancer risk with respect to tamoxifen treatment or particular radiation doses, trend tests for such effects were not significant.Our results indicate that some common risk variants associated with primary breast cancer also increase risk for contralateral breast cancer, and that these risks vary with the ER status of the first tumor.Patients with breast cancer are two to five times more likely to develop a second primary cancer in the contralateral breast than are unaffected women to develop an initial breast cancer [1-4]. Established risk factors for asynchronous second primary contralateral breast cancer (CBC) include those suggesting a genetic basis, suc
Patterns of Reproductive Isolation in Toads
John H. Malone, Brian E. Fontenot
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003900
Abstract: Understanding the general features of speciation is an important goal in evolutionary biology, and despite significant progress, several unresolved questions remain. We analyzed an extensive comparative dataset consisting of more than 1900 crosses between 92 species of toads to infer patterns of reproductive isolation. This unique dataset provides an opportunity to examine the strength of reproductive isolation, the development and sex ratios of hybrid offspring, patterns of fertility and infertility, and polyploidization in hybrids all in the context of genetic divergence between parental species. We found that the strength of intrinsic postzygotic isolation increases with genetic divergence, but relatively high levels of divergence are necessary before reproductive isolation is complete in toads. Fertilization rates were not correlated to genetic divergence, but hatching success, the number of larvae produced, and the percentage of tadpoles reaching metamorphosis were all inversely related with genetic divergence. Hybrids between species with lower levels of divergence developed to metamorphosis, while hybrids with higher levels of divergence stopped developing in gastrula and larval stages. Sex ratios of hybrid offspring were biased towards males in 70% of crosses and biased towards females in 30% of crosses. Hybrid females from crosses between closely related species were completely fertile, while approximately half (53%) of hybrid males were sterile, with sterility predicted by genetic divergence. The degree of abnormal ploidy in hybrids was positively related to genetic divergence between parental species, but surprisingly, polyploidization had no effect on patterns of asymmetrical inviability. We discuss explanations for these patterns, including the role of Haldane's rule in toads and anurans in general, and suggest mechanisms generating patterns of reproductive isolation in anurans.
Why California retailers stop selling tobacco products, and what their customers and employees think about it when they do: case studies
Patricia A McDaniel, Ruth E Malone
BMC Public Health , 2011, DOI: 10.1186/1471-2458-11-848
Abstract: We conducted case studies of seven California retailers (three grocery stores, four pharmacies) that had voluntarily ceased tobacco sales within the past 7 years. We interviewed owners, managers, and employees, conducted consumer focus groups, unobtrusively observed businesses and the surrounding environment, and examined any media coverage of each retailer's decision. We analyzed data using qualitative content analysis.For independent pharmacies, the only reason given for the decision to end tobacco sales was that tobacco caused disease and death. Grocers listed health among several factors, including regulatory pressures and wanting to be seen as "making a difference." Media coverage of stores' new policies was limited, and only three retailers alerted customers. Management reported few or no customer complaints and supportive or indifferent employees. Pharmacy employees were pleased to no longer be selling a deadly product. Grocery store management saw the decision to end tobacco sales as enhancing the stores' image and consistent with their inventory of healthy foods. Focus group participants (smokers and nonsmokers) were largely unaware that retailers had stopped selling tobacco; however, almost all supported the decision, viewing it as promoting public health. Many said knowing this made them more likely to shop at the store. Most thought that advertising the store's policy was essential to generate good public relations and tobacco norm changes.Voluntary retailer abandonment of tobacco sales both reflects and extends social norm changes that have problematized tobacco in California. Our findings suggest that such voluntary initiatives by retailers are welcomed by consumers and should be publicized, enhancing public health efforts.Approximately 40, 000 California retailers sell tobacco products [1]. Outlet density increases the likelihood of smoking among minors and adults [2,3], due partly to tobacco advertising in tobacco outlets, which normalizes and promot
“People over Profits”: Retailers Who Voluntarily Ended Tobacco Sales
Patricia A. McDaniel, Ruth E. Malone
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0085751
Abstract: Background Tobacco retailers are key players in the ongoing tobacco epidemic. Tobacco outlet density is linked to a greater likelihood of youth and adult smoking and greater difficulty quitting. While public policy efforts to address the tobacco problem at the retail level have been limited, some retailers have voluntarily ended tobacco sales. A previous pilot study examined this phenomenon in California, a state with a strong tobacco program focused on denormalizing smoking and the tobacco industry. We sought to learn what motivated retailers in other states to end tobacco sales and how the public and media responded. Methods We conducted interviews with owners, managers, or representatives of six grocery stores in New York and Ohio that had voluntarily ended tobacco sales since 2007. We also conducted unobtrusive observations at stores and analyzed media coverage of each retailer’s decision. Results Grocery store owners ended tobacco sales for two reasons, alone or in combination: health or ethics-related, including a desire to send a consistent health message to employees and customers, and business-related, including declining tobacco sales or poor fit with the store’s image. The decision to end sales often appeared to resolve troubling contradictions between retailers’ values and selling deadly products. New York retailers attributed declining sales to high state tobacco taxes. All reported largely positive customer reactions and most received media coverage. Forty-one percent of news items were letters to the editor or editorials; most (69%) supported the decision. Conclusion Voluntary decisions by retailers to abandon tobacco sales may lay the groundwork for mandatory policies and further denormalize tobacco. Our study also suggests that high tobacco taxes may have both direct and indirect effects on tobacco use. Highlighting the contradictions between being a responsible business and selling deadly products may support voluntary decisions by retailers to end tobacco sales.
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