Challenges in Interpreting Germline Mutations in BARD1 and ATM in Breast and Ovarian Cancer Patients

Next‐generation sequencing promotes identification of mutations in non‐BRCA1/2 genes in hereditary cancer families. The contribution of mutations in moderate penetrance genes to hereditary cancer risk is not well established. Here, we report a family with early onset breast and fallopian tube cancer that was identified as carrying germline mutations in BARD1 and ATM genes. Loss of heterozygosity studies suggest a causative role of the BARD1 mutation in the development of primary peritoneal cancer, but fail to confirm an association between germline ATM mutations and breast cancer development in this family. Complexities in interpreting implications of mutations in moderate‐risk cancer susceptibility genes are discussed.     

Nutrition and pharyngeal cancer: results from a case-control study in Spain

BACKGROUND: Oropharyngeal and hypopharyngeal cancer is increasing all over the world, frequently affecting more and more women and younger individuals and not only the typical 50- to 60-year-old heavy smoker and drinking man. In addition, 5-year overall survival rate remains poor (30% to 40% in most series), despite advances in treatment. Therefore, it is crucial to understand as accurately as possible the risk factors for these malignancies to improve primary prevention. METHODS: We report the results from a case-control study of pharyngeal cancer risk factors conducted in Spain involving 232 consecutive patients who were gender- and age-matched with 232 controls. Data were collected by interviewer-administered personal interview. RESULTS: Our results show that low intake of fruit, fruit juice, uncooked vegetables, dietary fiber-containing foods (legume and cereals), fish, milk, and dairy products is an independent risk factor for pharyngeal cancer and that high consumption of meat and fried foods also increases the risk once data are adjusted for tobacco smoking and alcohol drinking. CONCLUSIONS: Although findings for fruit, juice, and uncooked vegetables are in accordance with those from other authors and can be explained on a biologic basis, the relationship between pharyngeal cancer and dietary excess of saturated fatty acids needs experimental investigation. Findings for milk, dairy products, and fish also warrant more detailed epidemiologic research because of conflicting data reported in the literature and because of the reportedly ambiguous role of retinol in human cancers. No conclusive explanations for the protective effect of dietary fiber-containing foods can be put forward today. Our results are uniquely attributable to oropharyngeal and hypopharyngeal cancers because of the small size of our nasopharyngeal cancer subsample.     

Incidence and survival trends of lip,intra-oral cavity and tongue base cancers in south-east England

Background

Oral cavity cancers are on the increase in the UK. Understanding site-specific epidemiological trends is important for cancer control measures.This study demonstrates the changing epidemiological trends in lip, intra-oral cavity and tongue base cancers in south-east England from 1987 to 2006.

Aim: Methods

This was a retrospective study using anonymised data obtained from the Thames Cancer Registry (TCR) London. Data were analysed using SPSS v.17 and survival analyses with Kaplan-Meier and Cox regression. Age standardisation of the incidence rates was performed. It was conducted in south-east England, which has an average population of 12 million. The study analysed 9,318 cases (ICD-10 code C00–C06, C14). Kent Research Ethics Committee UK granted ethical approval.

Results

Oral cancers were more common in men, with male: female ratio of 1.6:1. Tongue cancers had the highest frequency at 3,088 (33.1%).Incidence varied with each cancer type. Mean incidence (per 1,000,000) ranged from 2.3 (lip cancer) to 13.8 (tongue cancer). There has been a statistically significant increase in incidence for cancers of the tongue base, other parts of tongue, gum and palate (p<0.001).Median survival time varied by sub-site, with lip cancer having the best median survival time (11.09 years) compared with tongue base cancer (2.42 years). Survival analyses showed worse prognosis for men, older age at diagnosis, and presence of synchronous tumours (p<0.001).

Conclusion

There is a rising incidence of tongue and tongue base, gum and palate cancers in south-east England with wide variability in survival. Oral cancer awareness and screening programmes should be encouraged.     

International variation in prostate cancer incidence and mortality rates

Context

Wide variation exists internationally for prostate cancer (PCa) rates due to differences in detection practices, treatment, and lifestyle and genetic factors.

Objective

We present contemporary variations in PCa incidence and mortality patterns across five continents using the most recent data from the International Agency for Research on Cancer.

Evidence acquisition

PCa incidence and mortality estimates for 2008 from GLOBOCAN are presented. We also examine recent trends in PCa incidence rates for 40 countries and mortality rates for 53 countries from 1985 and onward via join-point analyses using an augmented version of Cancer Incidence in Five Continents and the World Health Organization mortality database.

Evidence synthesis

Estimated PCa incidence rates remain most elevated in the highest resource counties worldwide including North America, Oceania, and western and northern Europe. Mortality rates tend to be higher in less developed regions of the world including parts of South America, the Caribbean, and sub-Saharan Africa. Increasing PCa incidence rates during the most recent decade were observed in 32 of the 40 countries examined, whereas trends tended to stabilize in 8 countries. In contrast, PCa mortality rates decreased in 27 of the 53 countries under study, whereas rates increased in 16 and remained stable in 10 countries.

Conclusions

PCa incidence rates increased in nearly all countries considered in this analysis except in a few high-income countries. In contrast, the increase in PCa mortality rates mainly occurred in lower resource settings, with declines largely confined to high-resource countries.     

Surgical outcomes and survival rates of colon cancer in children and young adults

IntroductionColon cancer in children and young adults is rare. We sought to compare outcomes and survival between patients ≤and>25 years of age with colon cancer.MethodsUsing the National Cancer Database, patients with colon cancer between 2004 and 2016 were identified. We included patients with histological codes consistent with invasive colon adenocarcinoma and excluded those missing data about treatment. Post-surgical outcomes and survival were compared.ResultsOf 531,462 patients meeting criteria, 947 were ≤25 years. Patients ≤25 had more advanced disease (stage III:44.4%vs33.4%, stage IV:27.5%vs.15.3%) and higher rates of total colectomy (8.9%vs.2.7%) and proctocolectomy (5.0%vs.0.0%) than those >25 years. Stage for stage, 5-year survival was higher in patients ≤25 than those >25years. On multivariate regression, age was not associated with increased risk of mortality while male sex and uninsured status were.ConclusionsDespite presenting with more advanced disease, patients ≤25 years with colon cancer had better survival than those >25 years.     

腹腔镜结直肠癌手术的应用现状与进展

Laparoscopic surgery for colorectal cancer has the advantages of minimal impairment of gastrointestinal and pulmonary function, less immunosuppression and shorter hospital stay, which had been appoved by evidence-based medicine. With the development of concepts and techniques of minimally invasive surgery, the combination of laparoscope and endoscope in the treatment of colorectal cancer has attracted surgeons' attention, and some conventional surgery techniques of colorectal-anal anastomosis have been adopted during laparoscopic colorectal resection, which make ultra-low anastomosis feasible. The aspects mentioned above will promote the further development of laparoscopic surgery for colorectal cancer.     

Testis and prostate cancer incidence in ethnic groups in South East England

International variations in the incidence of testis and prostate cancer are well established. Data from the USA have also shown differences between White and Black men; however, there has been little work on ethnicity and cancer incidence in the UK, due to incomplete ethnicity information in cancer registries. The Hospital Episode Statistics (HES) dataset has more complete information on self-assigned ethnicity for inpatients of English NHS hospitals. Data on 194 590 male patients resident in South East England diagnosed with cancer between 1998 and 2003 were extracted from the Thames Cancer Registry (TCR). Of these, ethnicity information from HES was obtained for 123 507 (63%), ethnicity information from TCR was available for a further 5909 (3%), and no ethnicity was available for 65 174 (33%). Compared with 'All White' men, testis cancer incidence was significantly lower in Indian, Pakistani, Bangladeshi, Other Asian, Black Caribbean, Black African, Other Black and Chinese men. Prostate cancer incidence was significantly increased in Black Caribbean, Black African, Other Black, Indian, Pakistani, Mixed White and Black Caribbean and Mixed White and Black African groups compared with 'All White' men. Bangladeshi and Chinese men had a significantly decreased incidence of prostate cancer. The incidence of prostate cancer in Indian and Pakistani men showed convergence towards the rates in the white population, suggesting the existence of modifiable risk factors in these men. Most other variations in these data are consistent with international comparisons, and indicate that genetic variations in susceptibility are very influential.     

Serum Progesterone Levels in Patients with Gastric and Colorectal Cancers

Abstract

Background: It is known that various malignant tissues possess progesterone receptors. It has been reported that the serum progesterone levels increase and show a prognostic significance in gastric carcinoma. We carried out a study to determine the serum progesterone level in gastric cancer, and colorectal cancer.

Methods: 140 of our patients were male and 56 female. We determined serum progesterone level in patients with gastric cancer, and colorectal cancer. Patients with benign diseases participated in the study as control group. Results: In male patients with gastric cancer (n = 90) and colorectal cancer (n = 50) the serum progesterone level was not significantly higher than in the control group (n = 80) (mean: 1.08 ± 0.73,1.08 ± 0.32 and 1.01 ± 0.38 ng/ml, respectively). Among the female patients with gastric cancer (n = 26) and colorectal cancer (n = 30), the serum progesterone level was also not significantly higher than in the control group (n = 30) (mean: 1.19 ± 0.77, 1.21 ± 0.72 and 1.12 ± 0.61 respectively). In males, the sensitivity of progesterone for gastric cancer was 55.5% and 64% for colorectal cancer with a specificity of 37.5%. In females, the sensitivity of progesterone for gastric cancer was 54% and 57% for colorectal patients with a specificity of 40%.

Conclusions: Serum progesterone level does not correlate with the presence or absence of gastric cancer or colorectal cancer, and it is not a useful tumour marker.     

Challenges and advances in the diagnosis,biology, and treatment of urothelial upper tract and bladder carcinomas

Urothelial carcinomas span the bladder, ureter, and renal pelvis, and while there had been stagnation in the field of drug approval for the past two decades, there is now accelerated and regular US FDA approval of 5 immunotherapy agents. However, patients who inherently do not respond or progress on such therapies still represent an area of increased unmet need. In this special Seminars issue, we explore varying aspects of bladder urothelial carcinoma treatment with targeted therapies, the unique presentation and challenges in the treatment of upper tract and renal pelvis tumors, as well as new and emerging diagnostic imaging tools for varying genitourinary cancers.     

肠道菌群在胃肠道肿瘤发生发展及治疗中作用的现状与展望

胃肠道是人体内菌群的储存库。肠道菌群与人体构成共生关系,不仅参与营养物质代谢、机体免疫系统的发育和肠道屏障功能等正常生理过程,也与人体的多种疾病发生进展特别是胃肠道肿瘤的发病密切相关。同时肠道菌群影响着肿瘤的放疗、化疗和免疫治疗的疗效和毒副反应。随着基因测序技术和生物信息学的发展和普及化,探索肠道菌群与胃肠道肿瘤发生发展及治疗的关系是近年来的研究热点并为胃肠道肿瘤的预防和诊治提供新的方法和思路。     

骨桥蛋白与妇科肿瘤的研究进展

骨桥蛋白是一种分泌型磷酸化糖蛋白,广泛存在于人体的组织及体液中,具有多种生物学功能,与肿瘤的生长、增殖、侵袭和转移密切相关,被认为是一种新的肿瘤标志物。近年来越来越多的研究表明骨桥蛋白在妇科肿瘤中的功能和作用。本文概述了骨桥蛋白的生物学特性及其在妇科肿瘤转移中的机制,阐述近年骨桥蛋白与妇科肿瘤相关性的研究及其在妇科肿瘤的早期诊断、疗效评价和预后监测的临床意义。     

Intensity-modulated radiation therapy in head and neck cancers: an update

Intensity-modulated radiation therapy (IMRT), an advent of three-dimensional conformal radiotherapy (3D CRT), has excited the profession of radiation oncology more than any other new invention since the introduction of the linear accelerator. Approximately 1000 articles have been published on this topic to date, more than 200 of which focus on head and neck cancer. IMRT is based on computer-optimized treatment planning and a computer-controlled treatment delivery system. The computer-driven technology generates dose distributions that sharply conform to the tumor target while minimizing the dose delivered to the surrounding normal tissues. The high dose volume that tailors to the 3D configuration of the tumor along with the ability to spare the nearby normal tissues allows the option of tumor dose escalation. The head and neck region is an ideal target for this new technology for several reasons. First, IMRT offers the potential for improved tumor control through delivery of high doses to the target volume. Second, because of sharp dose gradients, IMRT results in the relative sparing of normal structures, such as the parotid glands, in the head and neck region. Third, organ motion is virtually absent in the head and neck region so, with proper immobilization, treatment can be accurately delivered. Although this is a relatively new technology, single-institution retrospective studies show better dosimetric profiles compared with conventional radiation techniques, as well as excellent clinical results. Salivary gland sparing using IMRT has also resulted in reduced incidence and severity of xerostomia, and this has been tested in a randomized trial against conventional radiotherapy for early-stage nasopharyngeal cancer. The results do confirm that IMRT does decrease xerostomia compared with conventional radiotherapy.