An understanding of factors associated with interest in genetic counseling and intentions to obtain colorectal cancer susceptibility testing is an important foundation for developing education, counseling, and genetic services and policies.A survey was mailed to first-degree relatives of patients diagnosed with colorectal cancer. The respondents (n = 426, 77% response rate) are siblings and adult children of Caucasian, Japanese, and Hawaiian ethnicity. Data collection was guided by a conceptual framework and included questions on demographics, family cancer history, predisposing factors (cancer worry, perceived risk, well-being), and enabling factors (decision preferences, social support, and health care factors). Logistic regression analysis on two binary dependent variables (interest in counseling and intentions to get genetic testing) was performed using Generalized Estimating Equations to account for family clusters.Forty-five % of respondents were interested in genetic counseling, and 26% "definitely" intended to get genetic testing for colon cancer when available. For counseling interest, the most important predictors were education, Hawaiian ethnicity, cancer worry, and family support. Cancer worry, perceived risk, and age (older) were directly, and Japanese ethnicity was inversely, associated with testing intentions.High rates of interest in cancer genetic testing are similar to those found in other studies. Ethnic differences reveal a paradox between objective population risk (higher for Japanese) and greater concerns (among Hawaiians). The substantial lack of awareness of family history warrants further research. Culturally sensitive education and counseling are needed for managing the likely high demand for personalized information about hereditary cancer risk.
ABSTRACT Objective An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for sporadic CRC differs by anatomical subsite of the primary tumor has not been examined. Design To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48,214 CRC cases and 64,159 controls of European ancestry. We characterized effect heterogeneity at CRC risk loci using multinomial modeling. Results We identified 13 loci that reached genome-wide significance (P <5×10 −8 ) and that were not reported by previous GWAS for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. Conclusion Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumor. Significance of this study What is already known about this subject? Heterogeneity among colorectal cancer (CRC) tumors originating at different locations of the colorectum has been revealed in somatic genomes, epigenomes, and transcriptomes, and in some established environmental risk factors for CRC. Genome-wide association studies (GWAS) have identified over 100 genetic variants for overall CRC risk; however, a comprehensive analysis of the extent to which genetic risk factors differ by the anatomical sublocation of the primary tumor is lacking. What are the new findings? In this large consortium-based study, we analyzed clinical and genome-wide genotype data of 112,373 CRC cases and controls of European ancestry to comprehensively examine whether CRC case subgroups defined by anatomical sublocation have distinct germline genetic etiologies. We discovered 13 new loci at genome-wide significance ( P <5×10 −8 ) that were specific to certain anatomical sublocations and that were not reported by previous GWAS for overall CRC risk; multiple lines of evidence support strong candidate target genes at several of these loci, including PTGER3, LCT, MLH1, CDX1, KLF14, PYGL, BCL11B , and BMP7 . Systematic heterogeneity analysis of genetic risk variants for CRC identified thus far, revealed that the genetic architectures of proximal and distal CRC are partly distinct. Taken together, our results further support the idea that tumors arising in different anatomical sublocations of the colorectum may have distinct etiologies. How might it impact on clinical practice in the foreseeable future? Our results provide an informative resource for understanding the differential role that genes and pathways may play in the mechanisms of proximal and distal CRC carcinogenesis. The new insights into the etiologies of proximal and distal CRC may inform the development of new precision prevention strategies, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Our findings suggest that future studies of etiological risk factors for CRC and molecular mechanisms of carcinogenesis should take into consideration the anatomical sublocation of the colorectal tumor.
Granular cell tumors (GCTs) are rare neoplasms of neuroectodermal origin characterized by large polygonal cells with abundant eosinophilic and granular cytoplasm. GCTs rarely affect the lungs, with only a few cases reported in the literature. The pathophysiology of this Schwann cell-derived condition is not well understood but is thought to be due to recurring genetic mutations. GCTs have been linked with Noonan syndrome. Here, we report the case of a 17-year-old caucasian male who presented with partial upper airway obstruction due to a GCT. This case promotes awareness among pathologists and clinicians for this condition in the workup of patients presenting with upper airway obstruction.
Sarcoidosis is a multisystem, inflammatory granulomatous disease that rarely involves breast tissue. The pathophysiology of this chronic granulomatous condition is not well understood but is thought to be multifactorial, involving environmental influences causing an amplified immune response. A key histomorphology feature in sarcoidosis is the presence of non-necrotizing granulomas. In this case, we report a 41-year-old African-American man with a known history of sarcoidosis of the lung who presented with gynecomastia and bilateral breast tenderness with palpable nodules. Subsequent biopsy and microscopic examination of the breast nodules revealed diffuse involvement with non-necrotizing granulomas in both breasts. A final diagnosis of extensive sarcoidosis involving breast tissue was rendered after excluding other causes of non-necrotizing granulomas. The patient underwent a bilateral mastectomy to remove the breast nodules. This case discusses sarcoidosis involving an unusual site.
A multiple regression analysis was undertaken to examine the relationship between age at first pregnancy and recollected age at menarche and sociological variables in Caucasian, Japanese, Chinese and part-Hawaiian parous women living in Hawaii. The analysis was conducted using the medical history records of 1198 Caucasian, 1770 Japanese, 453 Chinese and 578 part-Hawaiian women. Age at first pregnancy varied significantly among ethnic groups. Initial results showed an apparent heterogeneity among ethnic groups in the effect of age at menarche on age at first pregnancy. Once appropriate controls for the linear and non-linear effects of year of birth were made, the effects of age at menarche on age at first pregnancy no longer varied significantly among ethnic groups. The observed secular trends in age at first pregnancy have varied widely among the four ethnic groups studied and appear unrelated to genetic background.
Journal Article The Association of Blood Pressure with Cancer Incidence in a Prospective Study Get access John S. Grove, John S. Grove 1Biostatistics Program Department of Public Health Sciences, School of Public Health, University of HawaiiHonolulu, HI Search for other works by this author on: Oxford Academic PubMed Google Scholar Abraham Nomura, Abraham Nomura 2Japan-Hawaii Cancer Study, Kuakini Medical CenterHonolulu, HI Reprint requests to Dr. Abraham Nomura at the Japan-Hawaii Cancer Study, 347 N Kuakini Street, Honolulu, HI 96817 Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard K. Severson, Richard K. Severson 3Divisions of Epidemiology and Pediatric Oncology, University of MinnesotaMinneapotis, MN Search for other works by this author on: Oxford Academic PubMed Google Scholar Grant N. Stemmermann Grant N. Stemmermann 2Japan-Hawaii Cancer Study, Kuakini Medical CenterHonolulu, HI Search for other works by this author on: Oxford Academic PubMed Google Scholar American Journal of Epidemiology, Volume 134, Issue 9, 1 November 1991, Pages 942–947, https://doi.org/10.1093/oxfordjournals.aje.a116178 Published: 01 November 1991 Article history Received: 10 January 1991 Revision received: 03 May 1991 Published: 01 November 1991
SummaryCharacteristics of menstruation and reproductive history were studied in 2331 Caucasian, 4097 Japanese and 1003 Chinese women living in Hawaii and born between 1900 and 1940. Irregular periods, heavy flow and menses lasting more than five days were reported significantly more often in Caucasians than in the other two groups. Canonical correlation and multiple-regression procedures revealed that parity, recalled age at menarche and year of birth were significantly associated to the menstrual descriptions reported, in complex ways, distinctive in each ethnic group. Some similarities in the relationship of reproductive history variables with particular menstruation characteristics were found in the Caucasian and Japanese groups. For example, increased parity was associated with increased menstrual bleeding in both Caucasians and Japanese, and later age at menarche was significantly correlated with irregular menses in these two groups.ZusammenfassungMerkmale der Menstruation und Reproduktionsgeschichte wurden bei 2331 weißen, 4097 japnischen und 1003 chinesischen Frauen untersucht, die in Hawaii leben und zwischen 1900 und 1940 geboren waren. Unregelmäßige Perioden, starker Ausfluß und Menses von mehr als 5 Tagen wurden bei Weißen signifikant häufiger berichtet als bei den beiden anderen Gruppen. Kanonische Korrelationen und multiple Regressionen zeigten, daß Geburtenrang, erinnertes Menarchealter und Geburtsjahr signifikant mit den Menstruationsbeschreibungen verknüpft waren, und zwar in komplexer Weise, außerdem typisch bei jeder ethnischen Gruppe. Einige Ähnlichkeit im Verhältnis der reproduktiven Geschichte mit bestimmten Menstruationsmerkmalen wurden zwischen der weißen und japanischen Gruppe gefunden. Aufsteigender Geburtenrang war sowohl bei Weißen als auch bei Japanerinnen mit verstärkter Menstruationsblutung verknüpft, und ein späteres Menarchealter war bei diesen beiden Gruppen signifikant mit unregelmäßigen Menses korreliert.RésuméLes caractéristiques de la menstruation et l'histoire reproductrice ont été étudiées chez 2331 Caucasiennes, 4097 Japonaises et 1003 Chinoises vivant à Hawaii et nées 1900 et 1940. Des périodes irrégulières, un flux abondant et des règlés durant plus de 5 jours ont été signalés significativement plus souvent par les Caucasiennes que par les deux autres groupes. Les procédures de corrélation canonique et de régression multiple ont révélé que lar parité, l'ăge souvenu à la ménarche et l'année de naissance étaient significativement associées aux descriptions faites des menstrues, de façon complexe, distincte dans chaque groups ethnique. Certaines similitudes dans la relation entre les variables d'histoire reproductrice et des caractéristiques particulières de la menstruation ont été trouvées dans les groupes caucasien et japonais. Par example, une parité croissante était associée avec un saignement menstruel accru chez les Caucasiennes comme chez les Japonaises, et un ăge plus tardif à la ménarche était significativement corrélé avec des règles irrégulières dans ces deux groupes.
