Showing papers on "Cancer published in 1993"
TL;DR: It is argued that this damage to DNA, protein, and lipid is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts.
Abstract: Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great.
6,007 citations
TL;DR: The FACT-G meets or exceeds all requirements for use in oncology clinical trials, including ease of administration, brevity, reliability, validity, and responsiveness to clinical change.
Abstract: PURPOSEWe developed and validated a brief, yet sensitive, 33-item general cancer quality-of-life (QL) measure for evaluating patients receiving cancer treatment, called the Functional Assessment of Cancer Therapy (FACT) scale.METHODS AND RESULTSThe five-phase validation process involved 854 patients with cancer and 15 oncology specialists. The initial pool of 370 overlapping items for breast, lung, and colorectal cancer was generated by open-ended interview with patients experienced with the symptoms of cancer and oncology professionals. Using preselected criteria, items were reduced to a 38-item general version. Factor and scaling analyses of these 38 items on 545 patients with mixed cancer diagnoses resulted in the 28-item FACT-general (FACT-G, version 2). In addition to a total score, this version produces subscale scores for physical, functional, social, and emotional well-being, as well as satisfaction with the treatment relationship. Coefficients of reliability and validity were uniformly high. The ...
5,232 citations
TL;DR: Cutting mortality in the annually screened group was accompanied by improved survival in those with colorectal cancer and a shift to detection at an earlier stage of cancer.
Abstract: Background Although tests for occult blood in the feces are widely used to screen for colorectal cancers, there is no conclusive evidence that they reduce mortality from this cause. We evaluated a fecal occult-blood test in a randomized trial and documented its effectiveness. Methods We randomly assigned 46,551 participants 50 to 80 years of age to screening for colorectal cancer once a year, to screening every two years, or to a control group. Participants who were screened submitted six guaiac-impregnated paper slides with two smears from each of three consecutive stools. About 83 percent of the slides were rehydrated. Participants who tested positive underwent a diagnostic evaluation that included colonoscopy. Vital status was ascertained for all participants over 13 years of follow-up. A committee determined causes of death. A single pathologist determined the stage of cancer for each tissue specimen. Differences in mortality from colorectal cancer, the primary study end point, were monitored with the...
3,199 citations
[...]
TL;DR: The clinical features of ovarian cancer and recent advances in postoperative management are described, including bilateral salpingo-oophorectomy in selected women.
Abstract: Patients with ovarian cancer usually present with advanced disease, and the disease is generally managed with surgical resection followed by platinum-based chemotherapy. Recent chemotherapeutic advances have led to improved survival, and a better understanding of genetic risk factors has permitted a tailored approach to preventive strategies, such as bilateral salpingo-oophorectomy in selected women. This review describes the clinical features of ovarian cancer and recent advances in postoperative management.
2,072 citations
TL;DR: Three to six mutations appear to be required to complete the process of cellular multiplication associated with gradual increases in tumor size, disorganization and malignancy in cancer.
1,890 citations
TL;DR: Findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population.
Abstract: Background Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers, including cancers of the esophagus and stomach. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian County, China, have one of the world's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients. Purpose We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian. Methods Individuals of ages 40-69 were recruited in 1985 from four Linxian communes. Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period. The subjects were randomly assigned to intervention groups according to a one-half replicate of a 2(4) factorial experimental design. This design enabled testing for the effects of four combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta carotene, vitamin E, and selenium. Doses ranged from one to two times U.S. Recommended Daily Allowances. Results A total of 2127 deaths occurred among trial participants during the intervention period. Cancer was the leading cause of death, with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%). Significantly (P = .03) lower total mortality (relative risk [RR] = 0.91; 95% confidence interval [CI] = 0.84-0.99) occurred among those receiving supplementation with beta carotene, vitamin E, and selenium. The reduction was mainly due to lower cancer rates (RR = 0.87; 95% CI = 0.75-1.00), especially stomach cancer (RR = 0.79; 95% CI = 0.64-0.99), with the reduced risk beginning to arise about 1-2 years after the start of supplementation with these vitamins and minerals. No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc, riboflavin and niacin, or vitamin C and molybdenum. Patterns of cancer incidence, on the basis of 1298 cases, generally resembled those for cancer mortality. Conclusions The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population. Implications The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements.
1,706 citations
TL;DR: The annual incidence rates and numbers of new cases of 18 different cancers have been estimated for the year 1985 in 24 areas of the world and tobacco smoking and chewing are almost certainly the major prevent able causes of cancer today.
Abstract: The annual incidence rates (crude and age-standardized) and numbers of new cases of 18 different cancers have been estimated for the year 1985 in 24 areas of the world. The total number of new cancer cases (excluding non-melanoma skin cancer) was 7.6 million, 52% of which occur in developing countries. The most common cancer in the world today is lung cancer, accounting for 17.6% of cancers of men worldwide, and 22% of cancers in men in the developed countries. Stomach cancer is now second in frequency (it was slightly more common than lung cancer in 1980) and breast cancer—by far the most important cancer of women (19.1% of the total)—is third. There are very large differences in the relative importance of the different cancers by world area. The major cancers of developed countries (other than the 3 already named) are cancers of the colon-rectum and prostate, and, in developing countries, cancers of the cervix uteri, mouth and pharynx, liver and oesophagus. The implications of these patterns for cancer control, and specifically prevention, are discussed. Tobacco smoking and chewing are almost certainly the major prevent able causes of cancer today.
1,685 citations
TL;DR: More research is needed into the etiologic roles of menstrual cycle characteristics, especially research examining the probability of prolonged exposure to both estrogens and progesterone concurrently.
Abstract: PIP: Early age at menarche, late age at menopause, and late age at first full-term pregnancy are linked to a modest increase in the risk of developing breast cancer. Some evidence suggests that the earlier the full-term pregnancy, the earlier the period of decreased susceptibility of breast tissue changes begins. Nulliparity is related to an increased risk for breast cancer diagnosed after 40 years old. Multiple full-term pregnancies decrease the risk of breast cancers diagnosed after 40 years regardless of the age at first birth. On the other hand, they may increase the risk for breast cancers diagnosed before 40 years old. Surgical removal of the ovaries protects against breast cancer. Breast feeding apparently protects against breast cancer in China, but a protective effect has not been established in the US. Other than shorter intervals between menstrual periods, which tend to increase the risk, research has not yet made clear the etiologic roles of menstrual cycle characteristics. Other unclear etiologic roles include increased intervals between births, spontaneous and induced abortion, infertility, multiple births at last pregnancy, and hypertension during pregnancy. Researchers tend to accept a mechanism to explain the epidemiologic characteristics of menstrual activity and the increased risk of breast cancer, but no mechanisms have emerged for the other likely risk factors. Greater exposure to estrogen and progesterone simultaneously are linked to early age at menarche, late age at menopause, and shorter menstrual cycle length. So far, data show that long-term combined estrogen/progestin hormone replacement therapy and long-term use of oral contraceptives increase the risk of breast cancer. Moderately increased risks linked to longterm estrogen replacement therapy and obesity in postmenopausal women indicate that estrogen alone influences breast cancer risk. Since much of the research on breast cancer risk factors are inconclusive, more research is needed, especially research examining the probability of prolonged exposure to both estrogens and progesterone concurrently.
1,417 citations
TL;DR: The p53 tumor-suppressor gene is the most striking example because it is mutated in about half of almost all types of cancer arising from a wide spectrum of tissues.
Abstract: The crucial differences between normal cells and cancer cells stem from discrete changes in specific genes controlling proliferation and tissue homeostasis. Over 100 such cancer-related genes have been discovered, several of which are implicated in the natural history of human cancer because they are consistently found to be mutated in tumors. The p53 tumor-suppressor gene is the most striking example because it is mutated in about half of almost all types of cancer arising from a wide spectrum of tissues. Other tumor-suppressor genes important in human cancers, such as adenomatous polyposis coli, Wilms' tumor type 1, and neurofibromatosis type 1, . . .
1,315 citations
Journal Article•
TL;DR: The results suggest that a gene(s) on chromosome 17q accounts for the majority of families in which both early-onset breast cancer and ovarian cancer occur but that other genes predisposing to breast cancer exist.
Abstract: Breast cancer is known to have an inherited component, consistent in some families with autosomal dominant inheritance; in such families the disease often occurs in association with ovarian cancer. Previous genetic linkage studies have established that in some such families disease occurrence is linked to markers on chromosome 17q. This paper reports the results of a collaborative linkage study involving 214 breast cancer families, including 57 breast-ovarian cancer families; this represents almost all the known families with 17q linkage data. Six markers on 17q, spanning approximately 30 cM, were typed in the families. The aims of the study were to define more precisely the localization of the disease gene, the extent of genetic heterogeneity and the characteristics of linked families and to estimate the penetrance of the 17q gene. Under the assumption of no genetic heterogeneity, the strongest linkage evidence was obtained with D17S588 (maximum LOD score [Zmax] = 21.68 at female recombination fraction [theta f] = .13) and D17S579 (Zmax = 13.02 at theta f = .16). Multipoint linkage analysis allowing for genetic heterogeneity provided evidence that the predisposing gene lies between the markers D17S588 and D17S250, an interval whose genetic length is estimated to be 8.3 cM in males and 18.0 cM in females. This position was supported over other intervals by odds of 66:1. The location of the gene with respect to D17S579 could not be determined unequivocally. Under the genetic model used in the analysis, the best estimate of the proportion of linked breast-ovarian cancer families was 1.0 (lower LOD-1 limit 0.79). In contrast, there was significant evidence of genetic heterogeneity among the families without ovarian cancer, with an estimated 45% being linked. These results suggest that a gene(s) on chromosome 17q accounts for the majority of families in which both early-onset breast cancer and ovarian cancer occur but that other genes predisposing to breast cancer exist. By examining the fit of the linkage data to different penetrance functions, the cumulative risk associated with the 17q gene was estimated to be 59% by age 50 years and 82% by age 70 years. The corresponding estimates for the breast-ovary families were 67% and 76%, and those for the families without ovarian cancer were 49% and 90%; these penetrance functions did not differ significantly from one another.
1,244 citations
TL;DR: The data show that the great majority of all grades of CIN can be attributed to HPV infection, particularly with the cancer-associated types of HPV.
Abstract: Given improvements in human papillomavirus (HPV) testing that have revealed a strong link between sexual activity history and cervical HPV infection the authors conducted a large case-control study of HPV and cervical intraepithelial neoplasia (CIN) to evaluate whether sexual behavior and the other established risk factors for CIN influence risk primarily via HPV infection. The authors studied 500 women with CIN and 500 control subjects receiving cytologic screening at Kaiser Permanente a large prepaid health plan in Portland Oregon. The established epidemiologic risk factors for CIN were assessed by telephone interview. The authors performed HPV testing of cervicovaginal lavage specimens by gene amplification using polymerase chain reaction with a consensus primer to target the L1 gene region of HPV. Unconditional logistic regression analysis was used to estimate relative risk of CIN and to adjust the epidemiologic associations for HPV test results to demonstrate whether the associations were mediated by HPV. The case subjects demonstrated the typical epidemiologic profile of CIN: they had more sex partners more cigarette smoking earlier ages at first sexual intercourse and lower socioeconomic status. Statistical adjustment for HPV infection substantially reduced the size of each of these case-control differences. 76% of cases could be attributed to HPV infection; the results of cytologic review suggested that the true percentage was even higher. Once HPV infection was taken into account an association of parity with risk of CIN was observed in both HPV-negative and HPV-positive women. The data show that the great majority of all grades of CIN can be attributed to HPV infection particularly with the cancer-associated types of HPV. In light of this conclusion the investigation of the natural history of HPV has preventive as well as etiologic importance. (authors)
[...]
TL;DR: A critical review of the relationship between tea consumption and human cancer risk is provided, covering basic chemistry and biochemical activity of tea, epidemiologic investigations, and laboratory studies, as well as possible directions for future research.
Abstract: Tea is one of the most popular beverages consumed worldwide. The relationship between tea consumption and human cancer incidence is an important concern. This topic has been studied in different populations by many investigators, but no clear-cut conclusion can be drawn. Whereas some studies have shown a protective effect of tea consumption against certain types of cancers, other studies have indicated an opposite effect. Our purpose is to provide a critical review of this topic, covering basic chemistry and biochemical activity of tea, epidemiologic investigations, and laboratory studies, as well as possible directions for future research. Studies have demonstrated either a lack of association between tea consumption and cancer incidence at specific organ sites or inconsistent results. On the other hand, many laboratory studies have demonstrated inhibitory effects of tea preparations and tea polyphenols against tumor formation and growth. This inhibitory activity is believed to be mainly due to the antioxidative and possible antiproliferative effects of polyphenolic compounds in green and black tea. These polyphenolics may also inhibit carcinogenesis by blocking the endogenous formation of N-nitroso compounds, suppressing the activation of carcinogens, and trapping of genotoxic agents. The effect of tea consumption on cancer is likely to depend on the causative factors of the specific cancer. Therefore, a protective effect observed on a certain cancer with a specific population may not be observable with a cancer of a different etiology. On the basis of this concept, we suggest future laboratory and epidemiologic studies to elucidate the relationship between tea consumption and human cancer risk.
TL;DR: The results of the various breast cell proliferation studies in relation to breast cancer are unclear and research identifying a molecular explanation would help in understanding the different findings.
Abstract: Epidemiologic studies suggest that ovarian hormones contribute to the development of breast cancer at all stages. Early menopause and premenopausal obesity reduces the risk while postmenopausal obesity and menopausal estrogen replacement therapy increases the risk. Combined oral contraceptives and Depo-Provera do not reduce the risk. It appears that estrogens and progestogens act through and with proto-oncogenes and growth factors to affect breast cell proliferation and breast cancer etiology. Animal studies suggest that estrogen causes interlobular ductal cell division and progesterone causes increased terminal duct lobular unit cell division in the luteal phase. Most breast carcinomas originate from terminal duct lobular unit cells. During pregnancy these cells fully multiply. Their reproduction is also increased during the luteal phase. Yet there is considerable interpersonal variation. No studies examining breast cell division have compared cell division rates with serum hormone concentrations however. The peak of mitosis occurs about 3 days before breast cell death in the late luteal and very early follicular phases. Other research suggests that breast stem cell proliferation is linked to breast cancer development. Endocrine therapy reduces mitotic activity indicating the estrogen and progesterone receptor content of breast cancers. Hormone-dependent breast cancer cell lines are all estrogen-dependent. Progesterone can block the estrogen-dependent cell lines which act like endometrial cells. The results of the various breast cell proliferation studies in relation to breast cancer are unclear and research identifying a molecular explanation would help in understanding the different findings.
TL;DR: Screening based on PSA identifies some men with prostate cancer who have a significantly increased proportion of organ-confined tumors compared with those detected through evaluation for an abnormal digital rectal examination alone.
Abstract: Objective. —To determine whether prostate-specific antigen (PSA)—based screening alters the proportion of organ-confined prostate cancers detected. Design. —A prospective, nonrandomized, serial PSA-based screening trial (follow-up from 6 to 37 months), and a concurrent comparison group. Setting. —Genera community outpatient screening program based at a university center. Patients. —The study group consisted of 10251 men aged 50 years and older (mean and median age, 63 years; mean and median age of patients who underwent biopsies, 66 years) who presented to a prostate cancer screening program and consented to phlebotomy. The comparison group consisted of 266 concurrently studied private patients in the same age range (mean and median age, 68 years) who were referred for prostatic ultrasonography and biopsy because of an abnormal digital rectal examination (DRE). Main Outcome Measure. —Proportion detected with clinically or pathologically advanced prostate cancer. Results. —The men were divided into three groups: the comparison group, the initial PSA-based screening group, and the serial PSA-based screening group. The proportions of prostate cancers detected that were clinically or pathologically advanced were as follows: comparison group, 57% (27/47); initial PSA-based screening group, 37% (91/244); and serial PSA-based screening group, 29% (37/ 129). Screened patients had a lower proportion of advanced cancers than the comparison group (χ 2 [2]=12.3; P =.002); this advantage was observed principally in patients younger than 70 years. Surgical staging revealed that the cancer was microscopically focal and well differentiated (possibly latent cancer) in 2.5% (1/40) of the nonscreened group, 2.9% (7/244) of the initially screened group, and 7.8% (10/129) of the serially screened group (generalized Fisher's Exact Test, P =.08). Conclusion. —Screening based on PSA identifies some men with prostate cancer who have a significantly increased proportion of organ-confined tumors compared with those detected through evaluation for an abnormal DRE alone. ( JAMA . 1993;270:948-954)
TL;DR: Results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease.
Abstract: Genetic linkage analysis was used to determine whether a specific chromosomal locus could be implicated in families with a history of early onset cancer but with no other unique features. Close linkage of disease to anonymous microsatellite markers on chromosome 2 was demonstrated in two large kindreds. The pairwise lod scores for linkage to marker D2S123 in these kindreds were 6.39 and 1.45 at zero recombination, and multipoint linkage with flanking markers resulted in lod scores of 6.47 and 6.01. These results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease.
Journal Article•
TL;DR: The data suggest that regular, prolonged use of aspirin may reduce the risk of fatal cancer of the esophagus, stomach, colon, and rectum and future epidemiological and basic research should examine all digestive tract cancers.
Abstract: Aspirin and other nonsteroidal antiinflammatory drugs inhibit prostaglandin synthesis and tumor growth in many experimental systems, but it is unclear which of these tumor models are relevant to humans. We have reported reduced risk of fatal colon cancer among persons who used aspirin in a large prospective study. This analysis examines other fatal cancers in relation to aspirin among 635,031 adults in that study who provided information in 1982 on the frequency and duration of their aspirin use and did not report cancer. Death rates were measured through 1988. Death rates decreased with more frequent aspirin use for cancers of the esophagus, stomach, colon, and rectum but not generally for other cancers. For each digestive tract cancer, death rates were approximately 40% lower among persons who used aspirin 16 times/month or more for at least 1 year compared to those who used no aspirin. The trend of decreasing risk with more frequent aspirin use was strongest among persons who had used aspirin for 10 years or more; it remained statistically significant, except for esophageal cancer, in multivariate analyses that adjusted for other known risk factors. Biases such as early detection or aspirin avoidance among cases do not appear to explain the results. Our data suggest that regular, prolonged use of aspirin may reduce the risk of fatal cancer of the esophagus, stomach, colon, and rectum. Future epidemiological and basic research should examine all digestive tract cancers in considering the chemopreventive or therapeutic potential of nonsteroidal antiinflammatory drugs.
TL;DR: Cutaneous metastases are not uncommon and frequently are the first sign of extranodal metastatic disease, particularly in patients with melanoma, breast cancer, or mucosal cancers of the head and neck.
Abstract: Background : Most previous studies have found that cutaneous metastases occur infrequently and are rarely present at the time the cancer is initially diagnosed. Objective: We studied patients with metastatic cancer to determine the overall frequency of skin metastases, the frequency that these were the first sign of extranodal disease, and the clinical and histologic features of the cutaneous lesions. Methods : A 10-year period of tumor registry files was searched for patients with metastatic carcinoma and melanoma. For patients with skin metastases, medical records and pathology reports were also examined. Results : Of 4020 patients with metastatic disease, 420 (10%) had cutaneous metastases; in 306 of them the skin metastases were the first sign of extranodal metastatic disease. Breast cancer and melanoma were the most common. Nodules were the most frequent clinical presentation, although inflammatory, cicatricial, and bullous lesions were also noted. Incisional metastases were common. Histologic findings most frequently revealed adenocarcinoma that was sometimes suggestive of the site of origin. After recognition of skin metastases, mean patient survival ranged from 1 to 34 months depending on tumor type. Conclusion : Cutaneous metastases are not uncommon and frequently are the first sign of extranodal metastatic disease, particularly in patients with melanoma, breast cancer, or mucosal cancers of the head and neck.
Journal Article•
TL;DR: Examination of the incidence and mechanism of TGF-alpha and EGFR overproduction in tumors and histologically normal mucosa excised from patients with squamous cell carcinoma of the head and neck to test this hypothetical mechanism of field cancerization found it to serve both as a marker for malignant transformation and as a target for preventive therapies.
Abstract: The squamous mucosa of patients who develop head and neck cancer is “condemned” or predisposed to disregulated growth as reflected by the high incidence of synchronous and metachronous primary tumors. We hypothesized that transformed and nontransformed mucosa from head and neck cancer patients would produce increased levels of transforming growth factor α (TGF-α) and its cell surface receptor, the epidermal growth factor receptor (EGFR), thereby contributing to this predisposition. Using molecular biological techniques, we examined the incidence and mechanism of TGF-α and EGFR overproduction in tumors and histologically normal mucosa excised from patients with squamous cell carcinoma of the head and neck (SCCHN) to test this hypothetical mechanism of field cancerization. Northern blot hybridization was used to evaluate the frequency of increased TGF-α and EGFR mRNA production in tissue excised from 24 patients with SCCHN and 10 cell lines compared with 7 control patients without cancer or a history of alcohol and tobacco use. Southern blot hybridization was used to examine for gene amplification. In patients with SCCHN, TGF-α mRNA was elevated by a mean of 5-fold in 95% of histologically “normal” mucosa samples ( P = 0.001) and by a mean of 5-fold in 87.5% of tumors ( P = 0.0001) while EGFR mRNA was elevated by a mean of 29-fold in 91% of histologically normal mucosa specimens ( P = 0.0005) and by a mean of 69-fold in 92% of tumors ( P = 0.0005), compared with mRNA levels in control normal mucosa. In 10 SCCHN cell lines, TGF-α mRNA was increased by a mean of 16-fold and EGFR mRNA levels were increased by a mean of 77-fold. Increased production of TGF-α and EGFR mRNA in the histologically normal mucosa of patients at risk for a primary or secondary head and neck cancer may serve both as a marker for malignant transformation and as a target for preventive therapies.
Journal Article•
TL;DR: Interestingly, no significant association was found between RER+ tumors and a general familial clustering of cancer, indicating that this phenomenon may be specific to certain types of tumors.
Abstract: Recent reports have suggested that one or more genes may cause replication errors (RER) during colorectal tumorigenesis. Additional alleles are seen in the tumors when analyzing random microsatellite loci. We have studied seven dinucleotide repeat loci, located on seven different chromosomes, by use of polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis. We found that 16.5% (40 of 243) colorectal cancers showed RER at one or several loci (RER+). This includes 31% (4 of 13) among cases with a strong positive family history according to previously published criteria and 17% (35 of 207) among cases with no history of familial cancer. Interestingly, no significant association was found between RER+ tumors and a general familial clustering of cancer. Microsatellite instability was significantly associated with DNA diploid status of the tumor ( P P P P = 0.05). We further analyzed 84 breast cancers and 86 male germ cell cancers using the same seven markers. None of the tumors were RER+, indicating that this phenomenon may be specific to certain types of tumors.
TL;DR: The authors calculated the probability at birth of having a diagnosis of prostate cancer within a man's life to be 8.8% and subtracted the incidence of microscopic Stage A cancers too small to ever be clinically significant.
Abstract: Background. Using the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute and American total mortality rates, the authors calculated the probability at birth of having a diagnosis of prostate cancer within a man's life to be 8.8% and then subtracted the incidence of microscopic Stage A cancers too small to ever be clinically significant. This gave a final probability of 8%. Methods. Prostates were examined after 139 consecutive unselected cystoprostatectomies from patients with bladder cancers in whom it was unknown whether they had prostate cancer
TL;DR: In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs, suggesting that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer.
Abstract: Background Organochlorines such as DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and PCBs (polychlorinated biphenyls), which have been used extensively as insecticides and as fluid insulators of electrical components, respectively, are known to be persistent environmental contaminants and animal carcinogens. These agents have been found in human tissue due to their inefficient metabolism and their solubility in lipids, which lead to lifelong sequestration in adipose tissue. Their association with human cancer occurrence, however, has been explored only marginally, with most studies having 20 or fewer cases. Purpose This blinded study was designed to determine whether exposure to PCBs and to DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the major metabolite of DDT, is associated with breast cancer risk in women. Methods We analyzed sera from the stored blood specimens of 14,290 participants enrolled between 1985 and 1991 in the New York University Women's Health Study, a prospective cohort study of hormones, diet, and cancer. Cohort members who developed breast cancer were included as case patients in our nested case-control study. DDE and PCBs were measured by gas chromatography in the sera of 58 women with a diagnosis of breast cancer 1-6 months after they entered the cohort and in 171 matched control subjects from the same study population who did not develop cancer. Results Mean levels of DDE and PCBs were higher for breast cancer case patients than for control subjects, but paired differences were statistically significant only for DDE (P = .031). After adjustment for first-degree family history of breast cancer, lifetime lactation, and age at first full-term pregnancy, conditional logistic regression analysis showed a fourfold increase in relative risk of breast cancer for an elevation of serum DDE concentrations from 2.0 ng/mL (10th percentile) to 19.1 ng/mL (90th percentile). For PCBs, the relative risk for a change in serum levels from 3.9 ng/mL (10th percentile) to 10.6 ng/mL (90th percentile) was less than twofold, a nonsignificant association that was further reduced after adjustment for DDE. Conclusion In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs. Implications These findings suggest that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer. Given the widespread dissemination of organochlorine insecticides in the environment and the food chain, the implications are far-reaching for public health intervention worldwide.
TL;DR: The knowledge about cancer pain and its treatment among physicians practicing in ECOG-affiliated institutions was determined to determine the methods of pain control being used by these physicians and to compare physician knowledge of and attitudes toward cancerPain with the results of a study of cancer pain.
Abstract: Objective: The Eastern Cooperative Oncology Group (ECOG) conducted a groupwide survey to determine the amount of knowledge about cancer pain and its treatment among physicians practicing in ECOG-af...
TL;DR: For women aged 40-49, randomized controlled trials consistently demonstrated no benefit from screening in the first 5-7 years after study entry, and only one trial (Health Insurance Plan) has data beyond 12 years of follow-up, and results showed a 25% decrease in mortality at 10-18 years.
Abstract: Background Over the past 30 years, eight major randomized controlled trials of breast cancer screening--with mammography and/or clinical breast examination--have been conducted. Results from several trials have been updated during the past year, and initial results of three other trials have been reported. Purpose The National Cancer Institute held an International Workshop on Screening for Breast Cancer in February 1993 to conduct a thorough and objective critical review of the world's most recent clinical trial data on breast cancer screening, consider the new evidence, assess the current state of knowledge, and identify issues needing further research. Methods Investigators representing the eight randomized controlled trials of breast cancer screening in women aged 40-74 presented published and unpublished data. Evidence relating to the effectiveness of breast cancer screening in different age groups, especially women aged 40-49, was presented. Results For women aged 40-49, randomized controlled trials consistently demonstrated no benefit from screening in the first 5-7 years after study entry. A meta-analysis of six trials found a relative risk of 1.08 (95% confidence interval = 0.85-1.39) after 7 years' follow-up. After 10-12 years of follow-up, none of four trials have found a statistically significant benefit in mortality; a combined analysis of Swedish studies showed a statistically insignificant 13% decrease in mortality at 12 years. Only one trial (Health Insurance Plan) has data beyond 12 years of follow-up, and results show a 25% decrease in mortality at 10-18 years. Statistical significance of this result is disputed, however. In women aged 50-69, all studies show mortality reductions; three of four studies show reductions of about 30% at 10-12 years after study entry. Results from two of these trials were statistically significant. Too few women over age 70 have been included in studies for adequate analysis. Conclusions For women aged 40-49, randomized controlled trials of breast cancer screening show no benefit 5-7 years after entry. At 10-12 years, benefit is uncertain and, if present, marginal; thereafter, it is unknown. For women aged 50-69, screening reduces breast cancer mortality by about a third. Currently available data for women age 70 or older are inadequate to judge the effectiveness of screening. Implications Randomized trials have provided stronger scientific evidence regarding the effectiveness of screening for breast cancer than for any other cancer. However, much still needs to be learned. Periodic gatherings of scientists in the field should speed the process.
TL;DR: For example, a simple summary of cancer mortality trends has been widely accepted as the most important measure of progress against cancer, since it reflects the impact of cancer on people, and has been considered less subject to distortion than incidence or survival as discussed by the authors.
Abstract: Time trends in cancer risk have often been summarised by the observation that mortality from cancers associated with tobacco is increasing rapidly, while mortality from all other cancers is either stable or falling slightly, this slight decline being dominated by the decrease in mortality from stomach cancer. Until recently, and with some variation between the sexes, this simple summary of cancer mortality trends would have been broadly correct for a number of developed countries, and it remains useful in dismissing claims of an impending and unexplained epidemic of cancer, but it does not apply to all countries, and in some there have recently been striking changes in the trends in mortality from cancers associated with tobacco. Cancer mortality has been widely accepted as the most important measure of progress against cancer, since it reflects the impact of cancer on people, and has been considered less subject to distortion than incidence or survival, although this is open to question. Cancer mortality also reflects trends in incidence and survival to a greater or lesser extent. There has been controversy, however, over how cancer mortality trends should be interpreted, as well as over which measures should be used to assess progress in cancer control. An overall summary of trends in mortality from all cancers combined is of limited value in assessing progress against cancer, in any case. Increases in a common lethal cancer may numerically dominate overall mortality trends, perhaps concealing declines in less common or less lethal cancers, while opposite trends in cancers of the lung and stomach, for example, might lead to an overall impression that little has changed. Further, up to a third of cancer patients will not die of cancer, and cancer mortality statistics do not reflect their experience at all. Cancer mortality trends only indirectly reflect trends in the number of people who are diagnosed with cancer in a given year, and those who do die of cancer in a given year may have been diagnosed more than 3 years previously, even though many die earlier: this blurs the responsiveness of routine cancer mortality statistics as a measure of recent progress, and alternative measures have been proposed. Trends in competing risks of death, especially at higher ages, may also complicate the interpretation of cancer mortality trends. The chance of developing cancer, and in that event, the chances of surviving it, are of direct interest to individuals.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: In this article, the p53 (also known as TP53) tumor suppressor gene encodes for a nuclear phosphoprotein thought to regulate proliferation of normal cells, and the relationship between levels of mutant p53 protein expression, tumor cell proliferation rate, and clinical outcome in patients with node-negative breast cancer was investigated.
Abstract: Background: The p53 (also known as TP53) tumor suppressor gene encodes for a nuclear phosphoprotein thought to regulate proliferation of normal cells. Most p53 mutations result in a nonfunctional protein that accumulates in tumor cell nuclei. These common mutations appear to be involved in the development and/or progression of several neoplastic diseases including human breast cancer. Purpose: Our purpose was to investigate the relationships between levels of mutant p53 protein expression, tumor cell proliferation rate, and clinical outcome in patients with node-negative breast cancer
TL;DR: Prostatic intraepithelial neoplasia and histological cancers are surprisingly common in young male patients of both races, and appears to present several decades earlier than clinically detected carcinoma.
TL;DR: The hypothesis that animal fat, especially fat from red meat, is associated with an elevated risk of advanced prostate cancer is supported and recommendations to lower intake of meat are supported to reduce the risk of prostate cancer.
Abstract: BACKGROUND The strong correlation between national consumption of fat and national rate of mortality from prostate cancer has raised the hypothesis that dietary fat increases the risk of this malignancy. Case-control and cohort studies have not consistently supported this hypothesis. PURPOSE We examined prospectively the relationship between prostate cancer and dietary fat, including specific fatty acids and dietary sources of fat. We examined the relationship of fat consumption to the incidence of advanced prostate cancer (stages C, D, or fatal cases) and to the total incidence of prostate cancer. METHODS We used data from the Health Professionals Follow-up Study, which is a prospective cohort of 51529 U.S. men, aged 40 through 75, who completed a validated food-frequency questionnaire in 1986. We sent follow-up questionnaires to the entire cohort in 1988 and 1990 to document new cases of a variety of diseases and to update exposure information. As of January 31, 1990, 300 new cases of prostate cancer, including 126 advanced cases, were documented in 47855 participants initially free of diagnosed cancer. The Mantel-Haenszel summary estimator was used to adjust for age and other potentially confounding variables. Multiple logistic regression was used to estimate relative risks (RRs) when controlling simultaneously for more than two covariates. RESULTS Total fat consumption was directly related to risk of advanced prostate cancer (age- and energy-adjusted RR = 1.79, with 95% confidence interval [CI] = 1.04-3.07, for high versus low quintile of intake; P [trend] = .06). This association was due primarily to animal fat (RR = 1.63; 95% CI = 0.95-2.78; P [trend] = .08), but not vegetable fat. Red meat represented the food group with the strongest positive association with advanced cancer (RR = 2.64; 95% CI = 1.21-5.77; P = .02). Fat from dairy products (with the exception of butter) or fish was unrelated to risk. Saturated fat, monounsaturated fat, and alpha-linolenic acid, but not linoleic acid, were associated with advanced prostate cancer risk; only the association with alpha-linolenic acid persisted when saturated fat, monounsaturated fat, linoleic acid, and alpha-linolenic acid were modeled simultaneously (multivariate RR = 3.43; 95% CI = 1.67-7.04; P [trend] = .002). CONCLUSION The results support the hypothesis that animal fat, especially fat from red meat, is associated with an elevated risk of advanced prostate cancer. IMPLICATIONS These findings support recommendations to lower intake of meat to reduce the risk of prostate cancer. The potential roles of carcinogens formed in cooking animal fat and of alpha-linolenic acid in the progression of prostate cancer need to be explored.
TL;DR: The genes that have been cloned act at diverse points in the signal transduction pathway in cells, from the outer cell membranes to sites of gene transcription, in some cases as negative regulators of oncogene expression.
Abstract: The antioncogenes, or tumor suppressor genes, as negative regulators of cell division, stand in contrast to oncogenes. For most human cancers, the more frequently mutated genes are the antioncogenes, the principal exception being the leukemias and lymphomas. Persons heterozygous for germ-line mutations in antioncogenes are strongly predisposed to one or more kinds of cancer, and most dominantly inherited cancer is attributable to such heterozygosity. Seven antioncogenes have been cloned through the study of these persons, and several others have been mapped. An eighth one was mapped and cloned through the investigation of tumors and is not yet known in hereditary form. Three dominantly inherited forms of cancer are not attributable to mutations in antioncogenes. The corresponding nonhereditary forms of most cancers generally reveal abnormalities of the same antioncogenes that are found in the hereditary forms but may also show additional ones. Some cancers, especially the embryonal tumors of children, have a small number of antioncogene mutations; some others, such as most sarcomas, have more, and the common carcinomas have the most, reflecting a hierarchy of controls over growth of stem cell populations. Still more members of this gene category remain to be mapped and cloned through the study of cancer families and of tumors. The genes that have been cloned act at diverse points in the signal transduction pathway in cells, from the outer cell membranes to sites of gene transcription, in some cases as negative regulators of oncogene expression.
TL;DR: This work has shown that in some but not all families with hereditary nonpolyposis colorectal cancer there is a high risk of certain cancers other than colon cancer.
Abstract: Published studies of families with hereditary nonpolyposis colorectal cancer (HNPCC) frequently report the occurrence of cancers at extracolonic sites. Our purpose in this study was to compare the observed frequency of cancer at specific sites in members of 18 unrelated HNPCC kindreds with expectations based on general population incidence in order to determine whether there were specific types of cancer for which family members were at elevated risk. We were able to stratify family members according to their risk of carrying the putative HNPCC gene. We found that putative HNPCC gene carriers and their high risk relatives have been diagnosed with cancers other than uterine and colorectal more frequently than expected based on general population incidence figures. Specific sites where elevations are seen include the stomach, small intestine, biliary system (especially the bile ducts), urological system (especially the kidney and ureter), and ovary.