Re: "The genetic passport".
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Breast Neoplasms↗
Biomedical subjects
A I Neugut
Publications and source records attributed to A I Neugut.
Risk factors for biliary tract cancers.
OBJECTIVE: Little is known regarding risk factors for biliary tract cancer, i.e., gallbladder carcinoma and extrahepatic bile duct carcinoma. This is the first case-control study conducted in the U.S. regarding risk factors for these cancers. METHODS: In this hospital-based case-control study, we reviewed the medical records of 69 patients with primary biliary tract cancer who were admitted to Columbia-Presbyterian Medical Center for surgery between January 1, 1980, and April 4, 1994, and of 138 controls, consisting of patients admitted for surgery for benign conditions. RESULTS: We found a significant association between cholelithiasis and biliary tract cancers (odds ratio, 19.5; 95% confidence interval, 6.4-59.4). Risk factors associated with gallbladder cancer included female gender, age, cigarette smoking, and postmenopausal status in women. Risk factors associated with extrahepatic bile duct cancer included history of cholecystectomy and hysterectomy in women. CONCLUSION: The risk factors for biliary tract cancers that have been identified in our study delineate a high-risk population, which in the future may be targeted for preventive measures.
Bile Duct Neoplasms↗
Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2.
PURPOSE: To determine the survival benefit and cost-effectiveness of screening Ashkenazi Jewish women for three specific BRCA1/2 gene mutations. METHODS: We used a Markov model and Monte Carlo analysis to estimate the survival benefit and cost-effectiveness of screening for three specific mutations in a population in which their prevalence is 2.5% and the associated cancer risks are 56% for breast cancer and 16% for ovarian cancer. We assumed that the sensitivity and specificity of the test were 98% and 99%, respectively, that bilateral prophylactic oophorectomy would reduce ovarian cancer risk by 45%, and that bilateral prophylactic mastectomy would reduce breast cancer risk by 90%. We used Medicare payment data for treatment costs and Surveillance, Epidemiology, and End Results data for cancer survival. RESULTS: Our model suggests that genetic screening of this population could prolong average nondiscounted survival by 38 days (95% probability interval, 22 to 57 days) for combined surgery, 33 days (95% probability interval, 18 to 43 days) for mastectomy, 11 days (95% probability interval, 4 to 25 days) for oophorectomy, and 6 days (95% probability interval, 3 to 8 days) for surveillance. The respective cost-effectiveness ratios per life-year saved, with a discount rate of 3%, are $20,717, $29,970, $72,780, and $134,273. CONCLUSION: In this Ashkenazi Jewish population, with a high prevalence of BRCA1/2 mutations, genetic screening may significantly increase average survival and, depending on costs and screening/treatment strategies, may be cost-effective by the standards of accepted cancer screening tests. According to our model, screening is cost-effective only if all women who test positive undergo prophylactic surgery. These estimates require confirmation through prospective observational studies and clinical trials.
Adult↗
Family history of colorectal adenomatous polyps and increased risk for colorectal cancer.
BACKGROUND: The risk for colorectal cancer among family members of patients with colorectal cancer is well established, but the risk among family members of patients with colorectal adenomas is less well established. OBJECTIVE: To examine the risk for colorectal cancer among first-degree relatives of patients with adenoma compared with that among first-degree relatives of controls without adenoma. DESIGN: Reconstructed cohort study. SETTING: Three university-based colonoscopy practices in New York City. PATIENTS: 1554 first-degree relatives of 244 patients with newly diagnosed adenomas and 2173 first-degree relatives of 362 endoscopically normal controls. MEASUREMENTS: Structured interviews were used to obtain family history. Adjusted relative risks (RR) were estimated from Cox proportional hazards regression models. RESULTS: The risk for colorectal cancer was elevated (RR, 1.74 [95% CI, 1.24 to 2.45]) among first-degree relatives of patients with newly diagnosed adenomas compared with the risk among first-degree relatives of controls. This increased risk was the same for parents (RR, 1.58 [CI, 1.07 to 2.34]) and siblings (RR, 1.58 [CI, 0.81 to 3.08]). First-degree relatives of patients with adenomas did not have elevated risk for other cancers. The risk for colorectal cancer among family members increased with decreasing age at diagnosis of adenoma in probands. Among first-degree relatives of patients who were 50 years of age or younger when the adenoma was diagnosed, the risk was more than four times greater (RR, 4.36 [CI, 2.24 to 8.51]) than that among first-degree relatives of patients who were older than 60 years of age when the adenoma was diagnosed. CONCLUSIONS: First-degree relatives of patients with newly diagnosed adenomas, particularly of patients who are 50 years of age or younger at diagnosis, are at increased risk for colorectal cancer and should undergo screening similar to that recommended for relatives of patients with colorectal cancer.
Adenomatous Polyposis Coli↗
Cigarette smoking and the colorectal adenoma-carcinoma sequence: a hypothesis to explain the paradox.
As recognized precursor lesions to colorectal cancer, colorectal adenomatous polyps have been studied to enhance knowledge of colorectal cancer etiology. Although most of the known risk factors for colorectal cancer are also associated with the occurrence of colorectal adenomas, cigarette smoking has had a strong, consistent relationship with colorectal adenomas but is generally not associated with colorectal cancer. The explanation for this paradox is unknown. With data collected in 1986-1988 during a large case-control study based on colonoscopy results in New York City, New York, the authors investigated the possibility that the paradox may arise because subjects with colorectal adenomas were included in the control group of cancer case-control studies. The authors found a statistically significant increased risk between heavy cigarette smoking (smokers with > or = 40 pack-years of smoking) and risk of adenoma (odds ratio (OR) = 1.61, 95% confidence interval (CI) 1.06-2.44). They saw no increased colorectal cancer risk from heavy cigarette smoking (OR = 1.02, 95% CI 0.52-1.99) using a "manufactured" control group to simulate a typical unscreened, population-based control group. When the authors compared these colorectal cancer cases with an adenoma-free control group examined by colonoscopy in a polytomous model with several case groups (newly diagnosed adenomas, carcinoma in situ, intramucosal carcinoma, and colorectal cancer), they found that the risk for 20-39 pack-years of smoking was elevated, although not statistically significant, and was similar for all four case groups. The risk for the highest smoking category (> or = 40 pack-years) was more strongly elevated in all four case groups, although it was statistically significant for only the newly diagnosed adenoma and the carcinoma in situ cases (adenomas, OR = 1.59, 95% CI 1.05-2.42; carcinoma in situ, OR = 2.05, 95% CI 1.01-4.15; intramucosal carcinoma, OR = 1.30, 95% CI 0.61-2.77; and colorectal cancer, OR = 1.30, 95% CI 0.64-2.65). While the authors' study is weakened by the lack of statistical significance concerning risk for colorectal cancer, these data offer some support for the hypothesis that the association between cigarette smoking and risk of colorectal cancer may have been masked by inclusion in the control group of subjects with adenomas. They also suggest that the major effect of smoking on the colorectal adenoma-carcinoma sequence occurs in the earlier stages of the formation of adenoma and the development of carcinoma in situ.
Adenoma↗
Radiation therapy for breast cancer and increased risk for esophageal carcinoma.
BACKGROUND: Several case reports have suggested an association between radiation therapy for breast cancer and the subsequent occurrence of esophageal carcinomas. OBJECTIVE: To examine the association between radiation therapy for breast cancer and subsequent esophageal squamous-cell carcinomas and adenocarcinomas. DESIGN: Population-based retrospective cohort study. SETTING: Population-based U.S. cancer registries. PATIENTS: 220,806 women in whom breast cancer was diagnosed between 1 January 1973 and 31 December 1993; 1,216,853 person-years of follow-up. MEASUREMENTS: Age- and period-adjusted standardized incidence ratio as a measure of relative risk for the second primary cancer. RESULTS: In women who had received radiation therapy for breast cancer, the relative risk for esophageal squamous-cell carcinoma increased to 5.42 (95% CI, 2.33 to 10.68) and the relative risk for esophageal adenocarcinoma increased to 4.22 (CI, 0.47 to 15.25) 10 or more years after radiation therapy. No increased risk was seen for either type of carcinoma among patients with breast cancer who did not receive radiation therapy. CONCLUSION: The risk for esophageal carcinoma is increased in women who receive radiation therapy for breast cancer.
Adenocarcinoma↗
Serum cholesterol and the risk of ductal carcinoma in situ: a case-control study.
While multiple studies have investigated the association between serum cholesterol level and breast cancer, the results have generally been conflicting. No prior study has investigated its association with ductal carcinoma in situ (DCIS) of the breast. In this hospital-based case-control study, 152 DCIS cases were compared to 242 controls (patients with benign surgical conditions). Unconditional logistic regression was used to compare the serum cholesterol levels, adjusting for relevant covariates. No statistically significant difference was observed for different quartiles of the serum cholesterol level as compared to the lowest quartile. Incidentally observed was an elevated risk for DCIS in postmenopausal versus premenopausal women, and in peri-menopausal versus premenopausal women. There is no apparent association between the serum cholesterol level and breast DCIS.
Adult↗
Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1-positive or BRCA2-positive patients.
PURPOSE: Young Ashkenazi Jewish women or those from high-risk families who test positive for BRCA1 or BRCA2 mutant genes have a significant risk of developing breast or ovarian cancer by the age of 70 years. Many question whether they should have prophylactic surgical procedures, ie, bilateral mastectomy and/or oophorectomy. METHODS: A Markov model was developed to determine the survival, quality of life, and cost-effectiveness of prophylactic surgical procedures. The probabilities of developing breast and ovarian cancer were based on literature review among women with the BRCA1 or BRCA2 gene and mortality rates were determined from Surveillance, Epidemiology, and End Results (SEER) data for 1973 to 1992. The costs for hospital and ambulatory care were estimated from Health Care Financing Administration (HCFA) payments in 1995, supplemented by managed care and fee-for-service data. Utility measures for quality-adjusted life-years (QALYs) were explicitly determined using the time-trade off method. Estimated risks for breast and ovarian cancer after prophylactic surgeries were obtained from the literature. RESULTS: For a 30-year-old woman, according to her cancer risks, prophylactic oophorectomy improved survival by 0.4 to 2.6 years; mastectomy, by 2.8 to 3.4 years; and mastectomy and oophorectomy, by 3.3 to 6.0 years over surveillance. The QALYs saved were 0.5 for oophorectomy and 1.9 for the combined procedures in the high-risk model. Prophylactic surgeries were cost-effective compared with surveillance for years of life saved, but not for QALYs. CONCLUSION: Among women who test positive for a BRCA1 or BRCA2 gene mutation, prophylactic surgery at a young age substantially improves survival, but unless genetic risk of cancer is high, provides no benefit for quality of life. Prophylactic surgery is cost-effective for years of life saved compared with other medical interventions that are deemed cost-effective.
Adult↗
The epidemiology of cancer of the small bowel.
Despite its anatomical location between two regions of high cancer risk, the small bowel rarely develops a malignant tumor. However, in recent years, small bowel cancer incidence rates have begun to rise. The purpose of this review is to explore the descriptive and analytic epidemiology of small bowel cancer for those factors that protect this organ and those factors associated with loss of this protection. Within the small intestine, the sites at the highest risk are the duodenum, for adenocarcinomas, and the ileum, for carcinoids and lymphomas. In industrialized countries, small bowel cancers are predominantly adenocarcinomas; in developing countries, lymphomas are much more common. The incidence of small bowel cancer rises with age and has generally been higher among males than among females. The risk factors for small bowel cancer include dietary factors similar to those implicated in large bowel cancer, cigarette smoking, alcohol intake, and other medical conditions, including Crohn's disease, familial adenomatous polyposis, cholecystectomy, peptic ulcer disease, and cystic fibrosis. The protective factors may include rapid cell turnover, a general absence of bacteria, an alkaline environment, and low levels of activating enzymes of precarcinogens. Adenocarcinomas of the small and large bowel are similar in risk factors and geographic distribution but not in recent time trends; colorectal cancer incidence rates in the United States have been falling since the mid-1980s. Small bowel lymphoma may be associated with infectious agents, such as HIV. Given the differences in anatomic and geographic location among histological subtypes, much may be learned from well-designed, histology-specific epidemiological and genetic studies of cancer of the small bowel.
Adenocarcinoma↗
Association between coronary heart disease and cancers of the breast, prostate, and colon.
Coronary heart disease (CHD) and cancers of the breast, prostate, and colon are more common in industrialized countries than in the developing world, and to some degree, these conditions appear to share risk factors. To investigate whether there is an association between these cancers and a prior history of CHD, a hospital-based case-control study was conducted at Columbia-Presbyterian Medical Center in New York. The study was based on 252 breast cancer cases, 256 colorectal cancer cases, and 322 benign surgical controls, all of whom underwent biopsy or surgery between January 1989 and December 1992, and on 319 prostate cancer cases and 189 benign prostatic hypertrophy controls diagnosed between January 1984 and December 1986 (prior to widespread use of prostate-specific antigen screening). Medical records were reviewed on each, focusing on the preoperative anesthesia and surgical clearances. No association was found between a history of CHD and breast or colorectal cancer, but an elevated risk was found for prostate cancer (odds ratio, 2.00; 95% confidence interval, 1.18-3.39), using unconditional logistic regression with adjustment for appropriate confounders. No association was found between cigarette smoking and any of the three cancers. Aspirin use was protective for colorectal cancer (odds ratio, 0.35; 95% confidence interval, 0.17-0.73) but had no association with breast or prostate cancer. The study suggests that individuals with CHD are at elevated risk for prostate cancer but not breast or colorectal cancer. Etiological risk factors associated with CHD should be investigated with regard to prostate cancer. Patients with CHD may represent a high-risk group for prostate cancer and potential future targets for prostate cancer screening interventions.
Aged↗
Incidence of malignant pleural mesothelioma after thoracic radiotherapy.
BACKGROUND: Although usually associated with asbestos exposure, a number of case reports have noted the occurrence of malignant pleural mesothelioma in patients who received radiotherapy (RT) to the thorax. METHODS: The authors performed a retrospective cohort study utilizing 251,750 women registered with breast carcinoma in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute from 1973-1993, 24.8% of whom received RT as part of their initial management, and 13,743 people with Hodgkin's disease, 50.6% of whom received RT as part of their initial management. RESULTS: Six cases of malignant pleural mesothelioma were found: two in breast carcinoma patients treated with RT and four found in women not treated with RT. No cases occurred in the patients with Hodgkin's disease. The overall estimated relative risk for malignant pleural mesothelioma after RT was 1.56 (95% confidence interval, 0.18-5.63). CONCLUSIONS: To the authors' knowledge, this is the first controlled study to investigate thoracic radiation exposure and malignant pleural mesothelioma, and no association was found.
Breast Neoplasms↗
Bladder carcinoma and other second malignancies after radiotherapy for prostate carcinoma.
BACKGROUND: Radiation therapy (RT) to the pelvis has been associated with an increased risk of bladder carcinoma, as well as other malignancies. However, no controlled studies have previously explored the risk of second malignancies after RT for prostate carcinoma. METHODS: A retrospective cohort study was conducted utilizing data from the Surveillance, Epidemiology, and End Results Program (SEER) of the U. S. National Cancer Institute from 1973-1990. The standardized incidence ratio (SIR), adjusted for age, was calculated as an estimate of the relative risk (RR) of developing a second malignancy after prostate carcinoma for radiated and nonradiated prostate carcinoma patients separately. RESULTS: The cohort was comprised of 34,889 prostate carcinoma patients who had undergone RT, and 106,872 who had not. After 8 years, the risk of bladder carcinoma was elevated for the RT group (RR 1.5; 95% confidence interval [CI], 1.1-2.0) but not for the non-RT group (RR 1.0; 95% CI, 0.7-1.2). There was an elevated risk of bladder carcinoma for the RT group at 5-8 years as well (RR 1.3; 95% CI, 1.0-1.7). No elevations in risk were observed for rectal carcinoma, acute nonlymphocytic leukemia, or chronic lymphocytic leukemia for either RT patients or non-RT patients. CONCLUSIONS: The risk of bladder carcinoma is elevated several years after RT for prostate carcinoma, but this elevation is not dramatic. There is no increased risk of rectal carcinoma or leukemia after this type of radiation exposure.
Aged↗
Analysis of the cost-effectiveness of paclitaxel as alternative combination therapy for advanced ovarian cancer.
PURPOSE: A phase III trial by the Gynecologic Oncology Group (GOG) provides strong evidence that a new alternative therapy--paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) in combination with cisplatin (Platinol; Bristol-Myers Squibb Co)--is clinically more effective than the standard therapy using cyclophosphamide (Cytoxan; Bristol-Myers Squibb Co) in combination with cisplatin in the treatment of advanced ovarian cancer. We conducted a pharmacoeconomic analysis to determine whether the alternative paclitaxel-cisplatin (TP) therapy is cost-effective (CE) in comparison to standard cyclophosphamide-cisplatin (CP) therapy. METHODS: Using an economic model, we applied cost data figures to resource utilization data derived from the two arms of the GOG trial. We examined paclitaxel benefits in terms of increased mean survival time, as well as median survival time. Estimates of the cumulative proportion surviving in the trial were based on Kaplan-Meier procedures. RESULTS: Per year of life gained (YLG), TP therapy costs more ($19,820 more for inpatient treatment; $21,222 outpatient) than CP treatment. CONCLUSION: The TP regimen's increased mean survival cost per YLG (inpatient and outpatient settings) adds a substantial benefit at an acceptable cost compared with CP therapy.
Antineoplastic Agents↗
An overview of adenocarcinoma of the small intestine.
Even though the small intestine contains 90% of the gastrointestinal tract mucosa and is located between the stomach and large intestine, two organs with a high cancer incidence, adenocarcinoma of the small intestine is 1/50th as common as adenocarcinoma of the large bowel. In several other respects, small-intestinal adenocarcinoma resembles large bowel adenocarcinoma; eg, it arises from adenomatous polyps, co-occurs in the same individuals, and has a similar pattern of incidence rates by country. Small-intestinal adenocarcinoma is diagnosed prior to surgery in only about 50% of cases and often occurs in conjunction with small bowel obstruction. The mainstay of treatment is surgery; prognosis depends on stage at presentation. Little is known about the use of radiotherapy and chemotherapy in this malignancy, but most physicians utilize therapeutic strategies modeled on the management of large-intestinal adenocarcinoma. Clarification of the reason for the low incidence of small-intestinal adenocarcinoma could lead to new interventions for the prevention of colorectal cancer.
Adenocarcinoma↗
Temporal variation in chlorinated hydrocarbons in healthy women.
Chlorinated hydrocarbons may increase breast cancer risk. Most epidemiological studies addressing this possibility have used one biological sample to measure a subject's cumulative exposure to these compounds. Little is known about short-term temporal variation in organochlorines, particularly in individuals with low levels. Thus, the reliability of using one sample to assess blood levels of chlorinated hydrocarbons in an epidemiological study is unknown. To better understand the temporal changes in blood measures among women with nonoccupational exposures to these compounds, we collected two 5-ml blood samples, an average of 2 months apart, from each of 31 nonfasting healthy women, ages 45-81 years. Samples were assayed for 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), polychlorinated biphenyls (PCBs), and trans-nonachlor in blinded, matched pairs. Results were adjusted for estimated total plasma lipids. The correlations between the two blood samples were high for DDE and PCBs (lipid-adjusted, r = 0.96 and r = 0.89, respectively). For trans-nonachlor, the correlation was relatively poor (lipid-adjusted r = 0.57); however, with the removal of one outlier, the correlation improved substantially (lipid-adjusted, r = 0.90). The mean difference between the two blood samples in unadjusted [-0.36 ng/ml, 95% confidence interval (CI), -0.97, 0.24 ng/ml, P = 0.23] and lipid-adjusted (-0.035 microgram/g lipid; 95% CI, -0.124, 0.055; P = 0.44) DDE levels was small. Similarly, there was little change in the mean difference for unadjusted (-0.14 ng/ml; 95% CI, -0.53, 0.25 ng/ml; P = 0.47) and lipid-adjusted (0.006 microgram/g lipid; 95% CI, -0.050, 0.062; P = 0.82) PCB levels. The mean differences in trans-nonachlor levels between the two blood draws were also small: unadjusted (-0.03 ng/ml; 95% CI, -0.07, 0.02 ng/ml; P = 0.20) and lipid-adjusted (-0.003 microgram/g lipid; 95% CI, -0.010, 0.004; P = 0.33). These data suggest that temporal changes in organochlorine levels within a 1 to 3-month period are minimal for noncancer patients and that a single measure for estimating exposure is highly reliable for DDE and PCB. For trans-nonachlor, however, where the correlation between blood draws was lower, three samples would be needed for estimating exposure; if an outlier is removed from our data, however, then we can conclude that only a single measure is sufficient. These data, therefore, offer no clear conclusion for the use of a single measurement for trans-nonachlor.
Aged↗
Prevalence and incidence of colorectal adenomas and cancer in asymptomatic persons.
The prevalence of colorectal adenomatous polyps varies widely from country to country and is highly correlated with colorectal cancer incidence rates in each country. The prevalence of adenomas reported in older studies was based on autopsy findings and is higher than that in more recent studies based on endoscopy findings. Among asymptomatic, average-risk patients, adenoma prevalence averages approximately 10% in sigmoidoscopy studies and more than 25% in colonoscopy studies, whereas the prevalence of colorectal cancer among these patients is less than 1%. The cumulative incidence of new adenomas within 3 years after normal endoscopy averages about 7% by flexible sigmoidoscopy and 27% by colonoscopy.
Adenoma↗
Cigarette smoking and large cell carcinoma of the lung.
Large cell carcinoma is the fourth most common histological type of lung cancer in the United States. Cigarette smoking causes large cell lung cancer, but it is uncertain whether the effect varies with the amount and duration of smoking. This uncertainty stems from ambiguity in the histopathological classification of large cell cancer, especially before 1971, and the relatively infrequent occurrence of large cell cancer in epidemiological studies. The present case-control investigation demonstrates that the risk of large cell cancer increases with both the frequency and number of years of cigarette smoking. The odds ratio associated with smoking two or more packs/day was 37.0 (95% confidence interval, 16.4-83.2) in men and 72.9 (35.4-150.2) in women. It is concluded that cigarette smoking is the predominant cause of large cell lung cancer.
Adult↗
Molecular genetics of small bowel cancer.
Although the molecular genetic changes that take place during carcinogenesis in the large bowel have been well elucidated, very little work has been done on the carcinogenesis process in the small bowel where this phenomenon is much rarer. The few studies that have been done to suggest that certain oncogenes, i.e., erbB2, K-ras, cyclin D1, and p53, are all altered in ways and in frequency similar to these phenomena in large bowel cancer. Some tumor markers have been noted to occur in malignant carcinoid tumours as well. Given the overall similarities in the epidemiology and the role of the adenoma-carcinoma sequence for both small bowel adenocarcinoma and colorectal adenocarcinoma, it is highly likely that the same molecular genetic changes play a major role. Further work is needed to confirm this. If true, a potentially important are of future research would be to determine why these molecular genetic changes occur so much less frequently in the small bowel as compared to the large bowel.
Animals↗