Second primary cancers after anogenital,skin, oral,esophageal and rectal cancers: Etiological links?

The Swedish Family-Cancer Database was used to analyze second cancers after oral, esophageal, rectal, cervical, genital and skin (squamous cell carcinoma) cancers. A strong and consistent association of second cancers was observed at all these sites, in men and women. As a novel finding, an association of rectal cancer with the human papillomavirus (HVP)-related cancers was shown. New evidence on an excess of skin cancer with the HPV-related cancers was also provided. As an epidemiological study, the associations were strong and often supported by a number of comparisons. These could not be explained by bias or long-term treatment related effects. However, whether the findings on rectal and skin cancer are due to HPV or other infections, transient or inherited depressed immune function or other constitutional factors remains to be established.     

Trends in in-patient Hospital Utilization and Surgical Procedures for Breast,Prostate, Lung and Colorectal Cancers in Canada

Objective: To analyse population-based trends of in-patient surgical procedures for breast (female), prostate, lung and colorectal cancers. Methods: The Hospital Morbidity Files supplied hospital data and the Canadian Cancer Registry, incidence data. Age-adjusted rates were standardized to the 1991 Canadian population. Results: All four cancers showed major changes in trends of surgical procedures. For breast cancer, the rate of in-patient breast conservation surgery (BCS) increased from 1981 to the early 1990s while the rate of mastectomy decreased. Because day surgery was not included, the subsequent in-patient BCS rate stayed level. For prostate cancer, the rate of transurethral prostatectomy was initially high but decreased after 1990, while the rate of radical prostatectomy increased rapidly, only minimally affected by the PSA-related peak in incidence. The lung cancer lobectomy rate in men remained at 10/100,000 after 1986, but in women rose from 3/100,000 to 7/100,000, reflecting increasing lung cancer incidence. For colorectal cancer, right hemicolectomies and anterior resections increased, especially in men. Conclusions: Surgery trends reflected changes in incidence and treatment preferences. Canadian trends were generally similar to US trends, although the timing of some of the changes differed. Canadians tended to use less invasive procedures such as BCS and anterior resection.     

A case report of quadruple cancer in a single patient including the breast, rectum, ovary, and endometrium

Multiple primary cancer is defined as the multiple occurrence of malignant neoplasms in the same individual. Due to the development of new diagnostic techniques and the rise in long-term survival of cancer, reports of multiple primary cancers have gradually increased. Herein, we describe the case of a 68-year-old female patient with quadruple primary cancer of the breast, rectum, ovary, and endometrium. For its great rarity, we report this case with a review of the literature.     

Rationale and design of the National Program of Cancer Registries' breast, colon, and prostate cancer patterns of care study

Background: Investigators from the Centers for Disease Control and Prevention (CDC), National Program of Cancer Registries (NPCR), are collaborating with public health professionals from seven states and the District of Columbia to conduct the Patterns of Care study to assess the quality of cancer data and to determine whether stage-specific treatments are being carried out. Methods: To assess the quality and completeness of cancer care data in the United States, trained staff from the Patterns of Care study are abstracting medical records to obtain detailed clinical data on treatment, tumor characteristics, stage at diagnosis, and demographics of representative samples of patients diagnosed with breast, colon, and prostate cancer. Altogether staff from each of the eight participating cancer registries will abstract 500 cases of breast, prostate, and colon/rectum/anus cancer for the CONCORD study and an additional 150 cases of localized breast cancer, 100 cases of stage III colon cancer, and 100 cases of localized prostate cancer for the Patterns of Care study. Chi-square tests will be used to compare routine registry data with re-abstracted data. The investigators will use logistic regression techniques to describe the characteristics of patients with localized breast and prostate cancer and stage III colon cancer. Age, race, sex, type of insurance, and comorbidity will be examined as predictors of the use of those treatments that are consistent with consensus guidelines. The investigators plan to use data from the CONCORD study to determine whether treatment factors are the reason for the reported differences between relative survival rates in the United States and Europe. Conclusions Results from the methodology used in the Patterns of Care study will provide, for the first time, detailed information about the quality and completeness of stage and treatment data that are routinely collected by states participating in the NPCR. It will add significantly to our understanding of factors that determine receipt of treatment in compliance with established guidelines. As part of the CONCORD study, it will also examine differences in survival among cancer patients with breast, prostate, and colon/rectum/anus cancers in the United States and Europe.     

Hereditary ovarian carcinoma: Heterogeneity,molecular genetics,pathology, and management

Hereditary ovarian cancer accounts for at least 5% of the estimated 22,000 new cases of this disease during 2009. During this same time, over 15,000 will die from malignancy ascribed to ovarian origin. The bulk of these hereditary cases fits the hereditary breast–ovarian cancer syndrome, while virtually all of the remainder will be consonant with the Lynch syndrome, disorders which are autosomal dominantly inherited. Advances in molecular genetics have led to the identification of BRCA1 and BRCA2 gene mutations which predispose to the hereditary breast–ovarian cancer syndrome, and mutations in mismatch repair genes, the most common of which are MSH2 and MLH1, which predispose to Lynch syndrome. These discoveries enable relatively certain diagnosis, limited only by their variable penetrance, so that identification of mutation carriers through a comprehensive cancer family history might be possible. This paper reviews the subject of hereditary ovarian cancer, with particular attention to its molecular genetic basis, its pathology, and its phenotypic/genotypic heterogeneity.     

Apolipoproteins,lipids and risk of cancer

The epidemiological evidence for an obesity‐cancer association is solid, whereas the association between obesity‐associated lipoprotein levels and cancer is less evident. We investigated circulating levels of Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), LDL‐cholesterol (LDL‐C) and HDL‐cholesterol (HDL‐C) and association to risk of overall cancer and common cancer forms. The Malmö Diet and Cancer Study, a population‐based prospective cohort study, enrolled 17,035 women and 11,063 men (1991–1996). Incident cancer cases were ascertained by record linkage with the Swedish Cancer Registry until end of follow‐up, January 1, 2012. Baseline serum levels of ApoA1 and ApoB were analyzed for the entire cohort and HDL‐C and LDL‐C levels in 5,281 participants. Hazard ratios, with 95% confidence interval, were calculated using Cox's proportional hazards analysis. In the entire cohort, none of the exposures were related to overall cancer risk (HR_adj ApoA1 = 0.98, 95%CI: 0.95,1.01; HR_adj ApoB = 1.01, 95%CI: 0.98–1.04). Among men, ApoB was positively associated with cancer risk (HR_adj ApoB = 1.06, 95%CI: 1.01,1.10). Female breast cancer risk was inversely associated with ApoB (HR_adj = 0.92, 95%CI: 0.86,0.99). Among both genders, ApoA1 was inversely associated with lung cancer risk (HR_adj = 0.88, 95%CI: 0.80,0.97), whereas high ApoB increased lung cancer risk (HR_adj = 1.08, 95%CI: 0.99,1.18). Colorectal cancer risk was increased with high ApoB (HR_adj = 1.08, 95%CI: 1.01,1.16) among both genders. Apolipoprotein levels were not associated with prostate cancer incidence. Circulating levels of apolipoproteins are associated with overall cancer risk in men and across both genders with breast, lung and colorectal cancer risk. Validation of these findings may facilitate future primary prevention strategies for cancer.     

Comparison of Crude and Age-Specific Incidence Rates of Breast,Ovary, Endometrium and Cervix Cancers in Iran, 2005

Background: Cancer accounts for 12.6% of total deaths in the world (just after heart disease). Materials andMethods: Frequency and age-specific incidence rates of breast and gynecologic cancers in Iran are calculatedbased on the dataset of the National Cancer Registry of Iran in 2005. Results: Gynecologic and breast canceraccounted for 7.6% and 25.6% of total cancer cases, respectively. Ovarian cancer was the most frequentgynecologic cancer followed by endometrium. Endometrial cancer revealed the highest age specific incidencerate followed by ovary (after 59 years). Conclusions: Regarding disease burden, breast and gynecologic casesaccount for 33.4% of total cancer patients. The age specific incidence rate is a useful guide in epidemiologic andfuture plans.     

Incidence of second primary cancers among survivors of childhood cancer: A population-based study,Osaka, Japan, 1975–2015

Second primary cancer (SPC) is one of the most life-threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population-based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0–14 years during 1975–2014 and survived 2 months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person-years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan–Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR = 28.0) followed by digestive system (EAR = 15.1), thyroid (EAR = 8.3), and bones and joints (EAR = 7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58-fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5-year and 10-year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk-based long-term follow-up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.     

Knowledge, attitudes, risk perception, and cancer screening behaviors among cancer survivors

BACKGROUND:

Knowledge, attitudes, and risk perception in relation to second primary cancer (SPC) screening and their impact on screening practices in cancer survivors are largely unknown.

METHODS:

A total of 326 cancer survivors who had completed primary treatment for cancer >1 year previously were recruited from 6 oncology care outpatient clinics in the Republic of Korea. Survivors' knowledge, attitudes, perceived risk, and screening practices were assessed along with sociodemographic, behavioral, and clinical characteristics. Multivariate logistic regression was used to examine behavioral factors associated with the completion of all appropriate SPC screening according to national guidelines.

RESULTS:

Approximately 37.7% of survivors had undergone all appropriate SPC screening tests. Survivors were found to have a high perceived risk of SPC, high perceived benefits of screening, and positive attitudes toward cancer screening. However, they had limited knowledge regarding SPC screening tests and few had received a recommendation from a physician to undergo SPC screening. Although there was no association found between perceived risk and positive attitudes with screening behavior, higher knowledge was noted to be significantly associated with the completion of all appropriate SPC screening (adjusted odds ratio, 1.81; 95% confidence interval, 1.03‐3.33).

CONCLUSIONS:

In the current study, cancer survivors were found to have limited knowledge regarding second cancer screening tests, which may have resulted in lower rates of completion of screening practices in this population. Cancer 2011. © 2011 American Cancer Society.     

Childhood and adolescent cancer statistics, 2014

In this article, the American Cancer Society provides estimates of the number of new cancer cases and deaths for children and adolescents in the United States and summarizes the most recent and comprehensive data on cancer incidence, mortality, and survival from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries (which are reported in detail for the first time here and include high‐quality data from 45 states and the District of Columbia, covering 90% of the US population). In 2014, an estimated 15,780 new cases of cancer will be diagnosed and 1960 deaths from cancer will occur among children and adolescents aged birth to 19 years. The annual incidence rate of cancer in children and adolescents is 186.6 per 1 million children aged birth to 19 years. Approximately 1 in 285 children will be diagnosed with cancer before age 20 years, and approximately 1 in 530 young adults between the ages of 20 and 39 years is a childhood cancer survivor. It is therefore likely that most pediatric and primary care practices will be involved in the diagnosis, treatment, and follow‐up of young patients and survivors. In addition to cancer statistics, this article will provide an overview of risk factors, symptoms, treatment, and long‐term and late effects for common pediatric cancers. CA Cancer J Clin 2014;64:83–103. ^© 2014 American Cancer Society.     

Type of Breast Cancer Diagnosis,Screening, and Survival

IntroductionBreast cancer screening is known to reduce mortality. In the present study, we analyzed the prevalence of breast cancers detected through screening, before and after introduction of an organized screening, and we evaluated the overall survival of these patients in comparison with women with an extrascreening imaging-detected breast cancer or those with palpable breast cancers.Materials and MethodsWe collected data about all women who underwent a breast operation for cancer in our department between 2001 and 2008, focusing on type of tumor diagnosis, tumor characteristics, therapies administered, and patient outcome in terms of overall survival, and recurrences. Data was analyzed by R (version 2.15.2), and P < .05 was considered significant.ResultsAmong the 2070 cases of invasive breast cancer we considered, 157 were detected by regional mammographic screening (group A), 843 by extrascreening breast imaging (group B: 507 by mammography and 336 by ultrasound), and 1070 by extrascreening breast objective examination (group C). The 5-year overall survival in groups A, B, and C were, respectively, 99% (95% CI, 98%-100%), 98% (95% CI, 97%-99%), and 91% (95% CI, 90%-93%), with a significant difference between the first 2 groups and the third (P < .05) and a trend between groups A and B (P = .081).ConclusionThe diagnosis of invasive breast cancer with screening in our population resulted in a survival gain at 5 years from the diagnosis, but a longer follow-up is necessary to confirm this data.     

Abridged republication of FIGO's staging classification for cancer of the ovary,fallopian tube,and peritoneum

Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture (“surgical spill”) is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB). Cancer 2015;121:3435–43. © 2015 American Cancer Society.     

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n=1186) of colon, 90.7% of gastric (n=473), and 87.2% of prostate cancers (n=414), and in 63.9% of lung cancers (n=1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (P<0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P=0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression.     

Nitrate in drinking water and the incidence of gastric, esophageal, and brain cancer in Yorkshire, England

Objectives: This small-area ecologic study in Yorkshire, northern England, examines the hypothesis that exposure to higher levels of nitrate in drinking water increases the risk of stomach, esophageal, or brain cancer in adults. Methods: Nitrate levels over the period 1990-95 and numbers of incident cancers from 1975-94 were available for 148 water supply zones, geographically defined areas each supplying water of homogeneous chemical composition to an average population of around 20,000. Results: No relationship was found between nitrate concentrations and the incidence of stomach or esophageal cancers. The incidence of cancer of the brain and central nervous system was found to be higher in areas with higher nitrate levels, with a relative risk of 1.18 (95 percent confidence interval = 1.08-1.30) in the quartile of the population with the highest average levels (mean 29.8 mg/l) compared with the lowest quartile (mean 2.4 mg/l). The increase in risk remained statistically significant (P < 0.01) after allowing for other covariates and for extra-Poisson variation in a regression model. Conclusions: This study does not support the hypothesis of an increased risk of stomach or esophageal cancer associated with higher nitrate levels in drinking water. The observed relationship with brain cancer requires confirmation in other studies, including those involving data on individuals.     

Novel antigens in non-small cell lung cancer: SP17, AKAP4, and PTTG1 are potential immunotherapeutic targets

Lung cancer is the leading cause of cancer deaths in both genders worldwide, with an incidence only second to prostate cancer in men and breast cancer in women. The lethality of the disease highlights the urgent need for innovative therapeutic options. Immunotherapy can afford efficient and specific targeting of tumor cells, improving efficacy and reducing the side effects of current therapies. We have previously reported the aberrant expression of cancer/testis antigens (CTAs) in tumors of unrelated histological origin. In this study we investigated the expression and immunogenicity of the CTAs, Sperm Protein 17 (SP17), A-kinase anchor protein 4 (AKAP4) and Pituitary Tumor Transforming Gene 1 (PTTG1) in human non-small cell lung cancer (NSCLC) cell lines and primary tumors. We found that SP17, AKAP4 and PTTG1 are aberrantly expressed in cancer samples, compared to normal lung cell lines and tissues. We established the immunogenicity of these CTAs by measuring CTA-specific autoantibodies in patients'' sera and generating CTA-specific autologous cytotoxic lymphocytes from patients'' peripheral blood mononuclear cells. Our results provide proof of principle that the CTAs SP17/AKAP4/PTTG1 are expressed in both human NSCLC cell lines and primary tumors and can elicit an immunogenic response in lung cancer patients.     

Cancer spectrum and frequency among children with Noonan,Costello, and cardio-facio-cutaneous syndromes

Background:

Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These ‘RASopathies'' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown.

Methods:

We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry.

Results:

We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR)=10.5, 95% confidence interval=5.4–18.3). The specific cancers included juvenile myelomonocytic leukaemia=4; brain tumour=3; acute lymphoblastic leukaemia=2; rhabdomyosarcoma=2; and neuroblastoma=1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4.

Conclusions:

These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours.