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The role of androgens and polymorphisms in the androgen receptor in the epidemiology of breast cancer
Elizabeth O Lillie, Leslie Bernstein, Giske Ursin
Breast Cancer Research , 2003, DOI: 10.1186/bcr593
Abstract: The role of androgens in breast cancer etiology has been a subject of both curiosity and confusion. It is still unclear by which mechanisms testosterone exerts its activity in the female breast, and whether the effects are predominantly proliferative or anti-proliferative on breast cells at physiologic levels. In the present review we evaluate the results from epidemiologic studies on the role of circulating testosterone and a functional polymorphism in the androgen receptor (AR) in breast cancer. We also highlight some of the epidemiologic challenges in addressing these questions.There are two main sources of androgens in women. Testosterone is produced directly by the ovary and by conversion of the adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone-sulfate into androstenedione, and then further to testosterone in peripheral tissue [1]. In premenopausal women, approximately 25% of circulating testosterone is secreted directly from the adrenal gland and 25% from the ovary, whereas the remaining 50% is produced by peripheral conversion of androstenedione [2]. Testosterone levels vary over the menstrual cycle with peak levels mid-cycle, and diurnally with highest levels in the early morning [3].Testosterone and androstenedione are produced by the interstitial cells of the ovarian stroma and may continue to respond to gonadotopins and produce testosterone after the menopause [4]. In normal postmenopausal women the ovarian vein has been observed to have higher concentrations of testosterone than is found in peripheral blood; bilateral oophorectomy results in reductions in testosterone levels by as much as 50% [5].Several smaller cross-sectional studies have found lower testosterone levels in postmenopausal than premenopausal women [6-8] or lower levels in perimenopausal than premenopausal women [2]. Large longitudinal studies that have followed women through the menopausal transition have observed either no significant change in testosterone [2,9] or a
Hormone-related risk factors for breast cancer in women under age 50 years by estrogen and progesterone receptor status: results from a case–control and a case–case comparison
Huiyan Ma, Leslie Bernstein, Ronald K Ross, Giske Ursin
Breast Cancer Research , 2006, DOI: 10.1186/bcr1514
Abstract: We evaluated the impact of age at menarche, pregnancy history, duration of breastfeeding, body mass index, combined oral contraceptive use, and alcohol consumption on breast cancer risk by ER/PR status in 1,725 population-based case patients and 440 control subjects aged 20 to 49 years identified within neighborhoods of case patients. We used multivariable unconditional logistic regression methods to conduct case–control comparisons overall as well as by ER/PR status of the cases, and to compare ER+PR+ with ER-PR- case patients.The number of full-term pregnancies was inversely associated with the risk of ER+PR+ breast cancer (ptrend = 0.005), whereas recent average alcohol consumption was associated with an increased risk of ER+PR+ breast cancer (ptrend = 0.03). Neither of these two factors was associated with the risk of ER- PR- breast cancer. Late age at menarche and a longer duration of breastfeeding were both associated with decreased breast cancer risk, irrespective of receptor status (all ptrend≤ 0.03).Our results suggest that the number of full-term pregnancies and recent alcohol consumption affect breast cancer risk in younger women predominantly through estrogen and progesterone mediated by their respective receptors. Late age at menarche and breastfeeding may act through different hormonal mechanisms.It has been well documented that estrogen and progesterone are important in breast tumorigenesis [1-3], and their effects on the breast are mediated by their respective receptors, the estrogen receptor (ER) and the progesterone receptor (PR) [4-7]. Furthermore, it has been hypothesized that hormone-related risk factors that reflect exposure to estrogen and progesterone may be predominantly associated with breast tumors that express ER and PR, but not with those lacking ER and PR expression [8-14]. Several epidemiological studies have examined this hypothesis by ER and PR status separately or jointly [15-17], and a review from 2004 [17] concluded that early age
Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies
Huiyan Ma, Leslie Bernstein, Malcolm C Pike, Giske Ursin
Breast Cancer Research , 2006, DOI: 10.1186/bcr1525
Abstract: We calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs) using a fixed effects model.Each birth reduced the risk of ER+PR+ cancer by 11% (RR per birth = 0.89, 95% CI = 0.84–0.94), and women who were in the highest age at first birth category had, on average, 27% higher risk of ER+PR+ cancer compared with women who were in the youngest age at first birth category (RR = 1.27, 95% CI = 1.07–1.50). Neither parity nor age at first birth was associated with the risk of ER-PR- cancer (RR per birth = 0.99, 95% CI = 0.94–1.05; RR of oldest versus youngest age at first birth category = 1.01, 95% CI = 0.85–1.20). Breastfeeding and late age at menarche decreased the risk of both receptor subtypes of breast cancer. The protective effect of late age at menarche was statistically significantly greater for ER+PR+ than ER-PR- cancer (RR = 0.72 for ER+PR+ cancer; RR = 0.84 for ER-PR- cancer, p for homogeneity = 0.006).Our findings suggest that breastfeeding (and age at menarche) may act through different hormonal mechanisms than do parity and age at first birth.Although it is well known that reproductive factors are associated with breast cancer risk [1-3], it is unclear to what extent these associations differ across subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status. There have been three narrative reviews of this topic [4-6]. The review published in 1986 [4] summarised the results from seven clinical case series and one hospital-based case-control study and did not find convincing evidence for any difference in effects of reproductive factors by ER status. The review published in 1993 [5] summarised the results from three population-based and four hospital-based case-control studies and concluded that nulliparity was positively associated with risk of ER+ breast cancer but not with ER- breast cancer. A review published in 2004 [6] summarised the epidemiological studies published by 2004 and concluded
Human Nail Clippings as a Source of DNA for Genetic Studies  [PDF]
Le Truong, Hannah Lui Park, Seong Sil Chang, Argyrios Ziogas, Susan L. Neuhausen, Sophia S. Wang, Leslie Bernstein, Hoda Anton-Culver
Open Journal of Epidemiology (OJEpi) , 2015, DOI: 10.4236/ojepi.2015.51006
Abstract: Blood samples have traditionally been used as the main source of DNA for genetic analysis. How-ever, this source can be difficult in terms of collection, transportation, and long-term storage. In this study, we investigated whether human nail clippings could be used as a source of DNA for SNP genotyping, null-allele detection, and whole-genome amplification. From extracted nail DNA, we achieved amplicons up to a length of ~400 bp and >96% concordance for SNP genotyping and 100% concordance for null-allele detection compared to DNA derived from matched blood sam-ples. For whole-genome amplification, OmniPlex performed better than Multiple Displacement Amplification with a success rate of 89.3% and 76.8% for SNP genotyping and null-allele detection, respectively. Concordance was ~98% for both methods. When combined with OmniPlex whole-genome amplification, human nail clippings could potentially be used as an alternative to whole blood as a less invasive and more convenient source of DNA for genotyping studies.
The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors - results of a prospective study
Huiyan Ma, Catherine L Carpenter, Jane Sullivan-Halley, Leslie Bernstein
BMC Cancer , 2011, DOI: 10.1186/1471-2407-11-222
Abstract: In 1999-2000, we collected the information of herbal remedy use and QOL during a telephone interview with 371 Los Angeles Non-Hispanic/Hispanic white women who had survived more than 10 years after breast cancer diagnosis. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) questionnaire. Patients were followed for mortality from the baseline interview through 2007. 299 surviving patients completed a second telephone interview on QOL in 2002-2004. We used multivariable Cox proportional hazards methods to estimate relative risks (RR) and 95% confidence intervals (CI) for mortality and applied multivariable linear regression models to compare average SF-36 change scores (follow-up - baseline) between herbal remedy users and non-users.Fifty-nine percent of participants were herbal remedy users at baseline. The most commonly used herbal remedies were echinacea, herbal teas, and ginko biloba. Herbal remedy use was associated with non-statistically significant increases in the risks for all-cause (44 deaths, RR = 1.28, 95% CI = 0.62-2.64) and breast cancer (33 deaths, RR = 1.78, 95% CI = 0.72-4.40) mortality. Both herbal remedy users' and non-users' mental component summary scores on the SF-36 increased similarly from the first survey to the second survey (P = 0.16), but herbal remedy users' physical component summary scores decreased more than those of non-users (-5.7 vs. -3.2, P = 0.02).Our data provide some evidence that herbal remedy use is associated with poorer survival and a poorer physical component score for health-related QOL among women who have survived breast cancer for at least 10 years. These conclusions are based on exploratory analyses of data from a prospective study using two-sided statistical tests with no correction for multiple testing and are limited by few deaths for mortality analysis and lack of information on when herbal remedy use was initiated or duration of or reasons for use.While the use of complementary and alternative
Genetic determinants of mammographic density
Christopher A Haiman, Leslie Bernstein, David Berg, Sue A Ingles, Martine Salane, Giske Ursin
Breast Cancer Research , 2002, DOI: 10.1186/bcr434
Abstract: In a cross-sectional study of 396 Caucasian and African-American women, we evaluated whether polymorphisms in genes involved in steroid hormone biosynthesis and metabolism, CYP17 (T27C), COMT (Val158Met), 17HSDB1 (Ser312Gly) and 3HSDB1 (Asn367Thr), predict mammographic density. We also evaluated whether associations vary by menopausal and hormone replacement therapy status.We found no strong consistent relationships between polymorphisms in these genes and breast density. African-American women homozygous for the Thr allele of 3HSDB1 had increased density (the absolute difference versus the Asn/Asn genotype was +19.7%; P trend = 0.02), while Caucasian homozygous women had decreased density (-5.1%; P trend = 0.04). Among premenopausal women, carriers of the Ser allele had (not significantly) greater density (versus Gly/Gly genotype: +7.1%; P trend = 0.07). In addition, among current users of hormone replacement therapy, we observed that women with the low-activity Met/Met genotype of COMT had greater breast density (versus the Val/Val genotype: +11.7%; P trend = 0.01).Additional large studies evaluating these and other candidate breast cancer genes will be required to determine what proportion, if any, of the interindividual differences in breast density are due to underlying genetic variation in genes involved in steroid hormone biosynthesis or metabolism.Breast density is one of the strongest independent predictors of breast cancer risk [1-5], and the extent of breast densities measured on a mammogram is correlated with a woman's menopausal status [6,7]. Premenopausal women have a considerably larger proportion of dense breast tissue than postmenopausal women, and in some women, breast density is greater during the luteal phase of the menstrual cycle when breast tissue is highly exposed to estradiol and progesterone [8]. Reducing circulating steroid hormone levels with a gonadotropin releasing hormone agonist [9,10], or antagonizing effects of estrogens on breast t
Taijin-Kyofu-Sho: A subtype of social anxiety  [PDF]
Leslie Lim
Open Journal of Psychiatry (OJPsych) , 2013, DOI: 10.4236/ojpsych.2013.34042

Taijin-Kyofu-Sho (TKS) has long been considered as a Japanese culture-bound form of social anxiety disorder, although subsequent case-reports from countries outside Japan have dispelled this notion. There are subtle yet distinct differences between TKS and DSM-defined social anxiety disorder (SAD). For instance, the TKS subject fears causing offence to others, whereas the SAD subject is more fearful of causing embarrassment to him/herself. Four sub-categories of TKS have been recognised of which the Jikoshu-kyofu variety resembles the olfactory reference syndrome (ORS) known to Western psychiatrists. There are two TKS subtypes, general (or simple) and offensive (delusional). The general subtype resembles social anxiety disorder, whereas the offensive subtype is characterised by delusions. True community-wide prevalence is unknown, although clinic studies estimate between 7.8% to 45.5% patients have a diagnosis of TKS, with a slight male preponderance. Cultural and societal norms engendering guilt, shame, and embarrassment are likely etiological factors. Treatment may consist of antidepressant and/or antipsychotic medications, while some patients may also benefit from cognitive behavior therapy.

Validation of a Questionnaire to Diagnose the Baumann Skin Type in All Ethnicities and in Various Geographic Locations  [PDF]
Leslie Baumann
Journal of Cosmetics, Dermatological Sciences and Applications (JCDSA) , 2016, DOI: 10.4236/jcdsa.2016.61005
Abstract: The Baumann Skin Typing System diagnoses patients as having one of 16 skin types based on their answers to a validated questionnaire [i] known as the Baumann Skin Type Indicator [ii]. The BSTI questionnaire has been tested over the last decade on over 200,000 people of various ages and ethnicities in different geographic locations around the world. In this study, data were collected from 52,862 patients to compare skin type prevalence between those who presented to doctor’s offices and those who took the quiz without supervision online. The most common skin types varied only slightly between patients that took the quiz online and those that completed the questionnaire in their doctor’s office. This indicates that the prevalence of skin types seen in the doctor’s office is similar to that in the general population and that supervision is not necessary to get an accurate result on the BSTI. [iii] In addition, comparison of data gathered in China, Korea, and the US did not show a significant difference in skin type prevalence between Asian and Caucasian skin types. [iv] This study demonstrates that the English version of the BSTI is valid for English speaking patients online, and in doctors’ offices in the US, China and Korea.
Reproductive Factors and Non-Hodgkin Lymphoma Risk in the California Teachers Study
Jennifer Prescott,Yani Lu,Ellen T. Chang,Jane Sullivan-Halley,Katherine D. Henderson,Christina A. Clarke,Huiyan Ma,Claire Templeman,Dennis Deapen,Leslie Bernstein
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008135
Abstract: Non-Hodgkin lymphoma (NHL) is a malignancy etiologically linked to immunomodulatory exposures and disorders. Endogenous female sex hormones may modify immune function and influence NHL risk. Few studies have examined associations between reproductive factors, which can serve as surrogates for such hormonal exposures, and NHL risk by subtype.
Epigenetic Subgroups of Esophageal and Gastric Adenocarcinoma with Differential GATA5 DNA Methylation Associated with Clinical and Lifestyle Factors
Xinhui Wang, Gyeong Hoon Kang, Mihaela Campan, Daniel J. Weisenberger, Tiffany I. Long, Wendy Cozen, Leslie Bernstein, Anna H. Wu, Kimberly D. Siegmund, Darryl Shibata, Peter W. Laird
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025985
Abstract: Background Adenocarcinomas located near the gastroesophageal junction have unclear etiology and are difficult to classify. We used DNA methylation analysis to identify subtype-specific markers and new subgroups of gastroesophageal adenocarcinomas, and studied their association with epidemiological risk factors and clinical outcomes. Methodology/Principal Findings We used logistic regression models and unsupervised hierarchical cluster analysis of 74 DNA methylation markers on 45 tumor samples (44 patients) of esophageal and gastric adenocarcinomas obtained from a population-based case-control study to uncover epigenetic markers and cluster groups of gastroesophageal adenocarcinomas. No distinct epigenetic differences were evident between subtypes of gastric and esophageal cancers. However, we identified two gastroesophageal adenocarcinoma subclusters based on DNA methylation profiles. Group membership was best predicted by GATA5 DNA methylation status. We analyzed the associations between these two epigenetic groups and exposure using logistic regression, and the associations with survival time using Cox regression in a larger set of 317 tumor samples (278 patients). There were more males with esophageal and gastric cardia cancers in Cluster Group 1 characterized by higher GATA5 DNA methylation values (all p<0.05). This group also showed associations of borderline statistical significance with having ever smoked (p-value = 0.07), high body mass index (p-value = 0.06), and symptoms of gastroesophageal reflux (p-value = 0.07). Subjects in cluster Group 1 showed better survival than those in Group 2 after adjusting for tumor differentiation grade, but this was not found to be independent of tumor stage. Conclusions/Significance DNA methylation profiling can be used in population-based studies to identify epigenetic subclasses of gastroesophageal adenocarcinomas and class-specific DNA methylation markers that can be linked to epidemiological data and clinical outcome. Two new epigenetic subgroups of gastroesophageal adenocarcinomas were identified that differ to some extent in their survival rates, risk factors of exposure, and GATA5 DNA methylation.
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