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Identification of occupational cancer risks in British Columbia. Part I: Methodology, descriptive results, and analysis of cancer risks, by cigarette smoking categories of 15,463 incident cancer cases.

To identify occupational cancer risk factors, lifetime occupational, smoking, and alcohol-consumption histories were collected by means of a self-administered questionnaire from 15,463 male cancer patients aged 20 years and over as ascertained from the British Columbia population-based cancer registry; all cases were histologically confirmed. The study methodology, descriptive results, and cancer risks from cigarette smoking are reported. Assessment of questionnaire validation and reliability showed very high correlations between all variables analysed. Non-response bias, assessed among 221 non-responders and 432 matched controls, revealed no statistically significant differences for smoking status, education, or for 11 usual (longest-held job) occupational groups, except for managerial occupations and for four pooled groups that represented 6.7% of all occupations. Except for pancreatic cancer, a significant relationship was found for all cancer sites known to be strongly associated with cigarette smoking.

Adult↗

Association between fertility drugs and gynecologic cancers, breast cancer, and childhood cancers.

Ovulation-inducing drugs have been widely used for various types of infertility since the beginning of 1960s and their use increases day by day parallel to the success achieved in fertility treatment. However, the researches performed in the last two decades have begun to discuss about the safety of these drugs and the risks associated with their use. Especially, the potential neoplastic effects of these drugs are increasingly questioned. The studies have discussed whether there is an association between the exposure to ovulation-inducing drugs and the incidence of various cancers. Moreover, several studies have been performed to reveal whether there is an increased risk of childhood cancers in children conceived after fertility treatment. The point we reached through the available data is that the risk of breast, uterine and invasive ovarian cancers is not increased, but the risk of borderline ovarian tumors might increase after such a therapy. The risk of cancer has been found similar for children conceived after fertility treatment and those conceived naturally. It should also be kept in mind that cancers are overdiagnosed in infertile women population because of the close medical surveillance, which may also contribute to the early detection of cancers. Although it is still early to state the last words on this topic, the possible association should be addressed when obtaining an informed consent before starting treatment.

Breast Neoplasms↗

Listening to the views of people affected by cancer about cancer research: an example of participatory research in setting the cancer research agenda.

AIM: The study 'Listening to the Views of People Affected by Cancer About Cancer Research' is currently exploring the views people affected by cancer have about cancer research and identifying their research priorities. Integral to this is the broader aim of ensuring an effective, collaborative participation of patients and carers in the design and conduct of the study. On the basis of experiences with the study to date, the latter is explored in this paper. DESIGN: The study adopts a 'participatory research' approach entailing the formation of a 'reference group' and a subsequent patient and carer co-researcher group. Patient and carer members of these groups were identified through the patient forums of UK cancer networks and by approaching 'hard to reach' representatives directly through community groups and participating study sites. FINDINGS: Experiences from this study illustrate that a 'participatory research' approach is appropriate in engaging patients and carers in the research process. Establishing a group of people affected by cancer in the study was found to be particularly effective in enhancing the design and conduct of the research. CONCLUSIONS: 'Participatory research' offers an effective means of involving patients and carers throughout the research process, thus strengthening the relevance and appropriateness of research findings and methods.

Adolescent↗

Increased risk of cancer among siblings of long-term childhood cancer survivors: a report from the childhood cancer survivor study.

We determined risk of cancer among first-degree relatives of 5-year survivors of childhood leukemia, lymphoma, central nervous system tumors, sarcomas, Wilms' tumor, and neuroblastoma. Subjects were 13,703 participants in the Childhood Cancer Survivor Study. Family history was collected on 56,759 first-degree relatives using a self-reported questionnaire. Incidence was compared with age- and sex-specific rates using the U.S. Surveillance, Epidemiology and End Results program. Siblings of the survivors had an increased risk of cancer [standardized incidence ratio (SIR), 1.5; 95% confidence interval (95% CI), 1.35-1.7]. Risk was elevated for siblings of probands of leukemia (SIR, 1.3; 95% CI, 1.0-1.6), Hodgkin's disease (SIR, 1.5; 95% CI, 1.2-1.9), non-Hodgkin's lymphoma (SIR, 1.8; 95% CI, 1.3-2.5), Wilms' tumor (SIR, 1.9; 95% CI, 1.2-3.2), soft tissue sarcoma (SIR, 1.5; 95% CI, 1.0-2.2), and bone tumors (SIR, 1.6; 95% CI, 1.2-2.2). Cancer risk was elevated in siblings (SIR, 2.4; 95% CI, 1.5-3.7) and offspring (SIR, 15.0; 95% CI, 5.3-42.9) of probands with second malignant neoplasms (SMN) compared with relatives of probands without SMNs. Siblings of probands with leukemia, Hodgkin's disease, neuroblastoma, and Wilms' tumor had elevated risks for the same malignancies. Parents had no increased risk (fathers' SIR, 0.7; 95% CI, 0.7-0.8; mothers' SIR, 0.9; 95% CI, 0.9-1.0). Seventy percent of siblings' cancers developed in adulthood. These findings suggest that familial cancer syndromes may be revealed as this cohort and family members age and with accrual of more offspring and subjects with SMNs.

Child↗

Growth hormone, IGF-I and cancer. Less intervention to avoid cancer? More intervention to prevent cancer?

The GH/IGF-I axis has a clearly established role in somatic growth regulation and there is much evidence suggesting that it can play a contributing role in neoplastic tissue growth; a number of recent epidemiological reports indicate that it may also be an important determinant of cancer incidence. Whilst there have been previous reports of changes to the axis in patients with established cancers, these new studies are distinct in being prospective and the inferences that can be made from this are outlined in this review. The recent studies are considered within the context of other indirect epidemiological evidence, and together indicate that the GH/IGF-I axis may establish the level of predisposition to a number of common cancers and indeed that such risk may be programmed from early life. There is considerable evidence for a number of possible mechanisms, both direct and indirect, which could account for the associations between GH/IGF-I levels and cancer incidence; these mechanisms are briefly summarised. The implications of the new findings are then discussed in relation to the increasing clinical usage of chronic GH administration and the need for further studies to establish any consequent increase in cancer risk. Finally the opportunities for further work to optimise cancer risk assessment and risk reduction strategies are highlighted.

Adult↗

A p53 genetic polymorphism of gastric cancer: difference between early gastric cancer and advanced gastric cancer.

AIM: To investigate the role of the polymorphism of p53 codon 72 in early gastric cancer (EGC) and advanced gastric cancer (AGC) in Korean patients. METHODS: DNA was extracted from blood samples of gastric cancer patients (n=291) and controls (n=216). In the p53 codon 72 genotypes were determined by PCR-RFLP. RESULTS: Patients with gastric cancer had a significantly higher frequency of the homozygous proline (Pro) allele than the control (P=0.032). Patients with AGC had a significantly higher frequency of the Arg/Arg (arginine) allele (P=0.038) than EGC and a similar Pro/Pro allele. The signet ring cell type had a higher frequency of the Pro/Pro allele than other types (P=0.031). The Pro/Pro genotype carries a 3.9-fold increased risk of developing gastric cancer (95% CI, 1.3-15.4, P=0.039) when compared to Arg/Arg and Arg/Pro genotypes and to develop EGC is a 5.25 fold increased risk (95% CI, 1.8-19.6, P=0.021). CONCLUSION: The Pro/Pro genotype of the p53 codon 72 polymorphism carries a higher risk for gastric cancer in general and is also associated with a much higher risk for EGC than AGC.

Adult↗

The relationship of socio-economic status and access to minimum expected therapy among female breast cancer patients in the National Cancer Institute Black-White Cancer Survival Study.

Black women are more likely to be diagnosed with later stage breast cancer and have higher mortality rates from breast cancer than white women. To determine whether cancer treatment varies for white and black women, we analyzed data from the National Cancer Institute (NCI) Black-White Cancer Survival Study (BWCSS). Data from hospital medical records, central review of histology slides, and patient interviews on 861 breast cancer cases (in situ and invasive) were examined. Minimum expected therapy was defined for each disease stage as a basic minimum course of treatment that incorporated current practice, state-of-the-art knowledge, and recommendations advanced by NIH Consensus Conferences up to and including the one held in 1985. Patients in this study were diagnosed during 1985-1986. Using logistic regression techniques, those who received at least the minimum expected therapy were compared to those who did not. Thirty-six percent of the patients with late stage disease did not receive minimum expected therapy compared to four percent of the patients with early stage disease. Older women and women with no usual source of care were significantly less likely to receive minimum expected therapy. Overall, 21% of black women did not receive minimum expected therapy compared to 15% of white women.

Adult↗

The Eighth AACR American Cancer Society Award lecture on cancer epidemiology and prevention. Genetically tailored preventive strategies: an effective plan for the twenty-first century? American Association for Cancer Research.

A preventive strategy of considerable appeal would offer specific lifestyle changes and preventive interventions to people at increased cancer risk because of inherited susceptibility. The hope for such a strategy stems in part from the variation in risk among carriers of cancer-predisposing mutations. For example, despite the high risks of cancers of the breast and ovary among BRCA1 and BRCA2 mutation carriers, some 30% of these women are estimated to reach age 70 years without developing either cancer. We need to know what protects these women, compared with carriers who do develop these malignancies. Apart from chance, possible explanations include variation in type of mutation, in genotypes at other loci, or in potentially modifiable lifestyle characteristics. This article reviews our present knowledge about risks for cancers of the colorectum, female breast, and ovary in carriers of highly penetrant germ-line mutations of susceptibility genes. The paper also reviews our present knowledge about options for reducing these risks through changes in lifestyle, chemopreventive agents, and prophylactic surgery. It concludes with a discussion of what we need to know to offer those with inherited susceptibility safe, effective options for preventing these cancers and to provide a framework for deciding among the options.

Breast Neoplasms↗

Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering.

To identify the major tumor suppressor gene (TSG) loci involved in the pathogenesis of lung cancer, we have conducted a high-resolution (10 cM), genome-wide search of loss of heterozygosity (LOH). Thirty-six lung cancer cell lines [14 small cell lung cancers (SCLCs) and 22 non-SCLCs (NSCLCs)] and their matched control DNAs were analyzed using 399 fluorescent microsatellite markers from the ABI Prism linkage mapping set v.2 on an ABI 377 sequencer/genotyper. Overall, 22 different regions with more than 60% LOH were identified: (a) 13 regions with a preference for SCLC; (b) 7 regions with a preference for NSCLC; and (c) 2 regions affecting both SCLC and NSCLC. The chromosomal arms with the most frequent LOH were 1p, 3p, 4p, 4q, 5q, 8p, 9p (p16), 9q, 10p, 10q, 13q (Rb), 15q, 17p (p53), 18q, 19p, Xp, Xq. In addition, new homozygous deletions were found at 2p23, 8q24, 18q11, and Xq22. On average, 34% (SCLC) to 36% (NSCLC) of markers showed allele loss in individual tumors, with an average size of subchromosomal region of loss of five to six markers (50-60 cM). Whereas SCLC and NSCLC had different regions of frequent LOH (hot spots), and NSCLC had more of these regions (n = 22) than SCLC (n = 17), in all other parameters (fractional allelic loss, number of breakpoints, and number of microsatellite alterations), SCLC and NSCLC were not significantly different. Clustering analysis revealed correlations between LOH on different chromosomes that suggest previously unknown genetic interactions for lung cancer development. We conclude that (a) in lung cancer cell lines, at least 17-22 chromosomal regions with frequent allele loss are involved, suggesting that the same number of putative TSGs are inactivated; (b) SCLC and NSCLC frequently undergo different specific genetic alterations; and (c) clusters of TSGs are likely to be inactivated together. Overall, these data provide global estimates of the extent of genetic changes leading to lung cancer and will be useful for the positional cloning of new TSGs and for the identification of multiple new biomarkers for translational research.

Alleles↗

[Cancer procoagulant activity in cases of esophageal, stomach and colorectal cancer considering progression degree and histological type of cancer].

The cancer procoagulant activity has been evaluated in homogenates of esophagal, stomach and colorectal cancer tissues and in the blood serum of patients with these neoplasms's. Activity of CP was significantly higher in examined material than in control. The correlation between CP activity and progression degree as well as histological type was affirmed. The higher activity of CP in homogenates as well as in serum was observed in cases with higher degree of clinical progression and smaller activity of this enzyme corresponded with lower degree of the cancer progression. The highest activity of CP was observed in the cases of adenocarcinoma whereas the lowest in cases of squamous cell carcinoma. Higher activity of CP in homogenates of examined tissues correlated with higher activity of this enzyme in the serum. Activity of CP depended on the tissue localisation of the cancer and the highest was in the cases of stomach cancers whereas the lowest was in the cases of esophagal cancer.

Adenocarcinoma↗

A pilot study of weekly docetaxel therapy for recurrent ovarian cancer, tubal cancer, and primary peritoneal cancer.

We investigated the efficacy and toxicity of salvage chemotherapy with weekly docetaxel for recurrent ovarian cancer, tubal cancer, and primary peritoneal cancer after treatment with regimens containing platinum or paclitaxel. The 15 subjects were managed as outpatients and received at least two courses of docetaxel therapy (35 mg/m2 on days 1, 8 and 15). Antitumour activity was assessed radiologically and from the CA-125 level. Among five patients with measurable lesions, one showed partial remission and three showed stable disease. Based on CA-125 levels, there were three partial remissions and five patients with stable disease (progression-free survival was 7.5 months and 7.6 months, respectively). During 61 courses, the severe toxicities were grade 3 leukopaenia/neutropaenia (6.7%) or grade 2 oedema and pleural effusion (13.3%). Weekly docetaxel may be useful salvage chemotherapy for recurrent ovarian cancer, tubal cancer, and peritoneal cancer, especially as tumour dormancy therapy.

Adult↗

Workshop report from the Division of Cancer Etiology, National Cancer Institute, National Institutes of Health. Protease inhibitors as cancer chemopreventive agents.

This workshop was organized to discuss the current state of research on anticarcinogenic protease inhibitors with regard to their potential use as human cancer chemopreventive agents. Previous studies have indicated that protease inhibitors can be powerful anticarcinogenic agents for animals and cells in culture and that human populations known to have high concentrations of protease inhibitors in the diet have low overall cancer mortality rates. In the workshop discussions, emphasis was placed on certain dietary protease inhibitors, such as the soybean-derived Bowman-Birk inhibitor and chymotrypsin inhibitor 1 from potatoes and some of the highly purified protease inhibitors of microbial origin provided by the Japan Society for the Promotion of Science, which have already been shown to contain anticarcinogenic activity in laboratory studies. Potential adverse side effects of dietary protease inhibitors were also considered, specifically, their possible effects on the pancreas and in causing decreased growth rates in young organisms. It was pointed out that the pancreata of a few species, notably rats and chicks, are extraordinarily sensitive to dietary protease inhibitors. Rats fed diets containing high concentrations of soybean-derived protease inhibitors (raw soy flour) had enlarged pancreata; increased pancreatic growth is thought to accelerate cancer development in the pancreas. The effect of raw soy flour on the growth of the rat pancreas has not been shown to occur in most other species tested (examples include hamsters, mice, dogs, pigs, and monkeys) and is not expected to occur in humans. There is no evidence that dietary protease inhibitors have adverse effects on the human pancreas. In fact, it has been observed that human populations with high levels of dietary protease inhibitors have decreased rates of pancreatic cancer. Dietary concentrations of protease inhibitors which have been shown to be anticarcinogenic have not produced decreased growth rates in animals or any type of pancreatic pathology. In general, there was a high level of enthusiasm at the workshop for the further development of protease inhibitors as chemopreventive agents. Recommendations for future research include: (a) research and development of sources of protease inhibitors; (b) analysis of human foods for protease inhibitor content; (c) evaluation of cancer incidence data in relation to protease inhibitor content and characteristics in the diet of human populations; (d) animal studies on the efficacy of protease inhibitors in cancer prevention; and (e) studies on the mechanism of action of anticarcinogenic protease inhibitors.

Humans↗

Update in cancer chemotherapy: genitourinary tract cancer, Part 4: Testicular cancer.

An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series: included are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 4 is a review of treatments for cancer of the testicles.Testicular cancer is highly curable and responds well to both surgery and chemotherapy. Patients with stage I and stage II nonseminomatous germ-cell tumors may be cured by surgery alone or in combination with chemotherapy. In patients with pathologic stage II disease, the use of adjuvant chemotherapy with two courses of platinum-based combination drugs has been successful in preventing relapse. Further refinements in management and research could banish the problem of testicular cancer.

Antineoplastic Agents↗

Update in cancer chemotherapy: gastrointestinal cancer--colorectal cancer, Part 2.

An update of the state of the art of cancer chemotherapeutic treatment of gastrointestinal tract cancer is described in a multi-part series. Part 1 surveyed colorectal cancer and the use of single-agent chemotherapy in the April issue of the Journal. Part 2 of colorectal cancer will describe combination chemotherapy, preoperative and postoperative radiation, and combinations of chemotherapy and radiation, and adjuvant chemotherapy.In advanced gastrointestinal tract cancer, chemotherapy is only of palliative value with response rates generally under 50 percent and survival rates of several months to one year or more. Combination chemotherapy often produces higher response rates, yet there is no acceptable evidence that survival is improved. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers may be due to lack of data.

Antineoplastic Combined Chemotherapy Protocols↗

Update in cancer chemotherapy: gastrointestinal cancer--colorectal cancer, Part 1.

An update of the state of the art of cancer chemotherapeutic treatment of gastrointestinal tract cancer is described. A review of cancers of the colon, rectum, anus, pancreas, stomach, small intestine, biliary passages, liver, and esophagus will be published in a multiple-part series. Part 1 will survey colorectal cancer and the use of single-agent chemotherapy.In advanced gastrointestinal tract cancer, chemotherapy is only of palliative value with response rates generally under 50 percent and with duration of several months to one year or more. Combination chemotherapy often produces higher response rates, yet there is no acceptable evidence that survival is improved. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers may be due to lack of data.

Antineoplastic Agents↗

Early detection of prostate cancer following repeated examinations by multiple modalities: results of the American Cancer Society National Prostate Cancer Detection Project.

The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multicenter, interdisciplinary demonstration project to assess the impact on early detection of transrectal ultrasound (TRUS), prostate-specific antigen (PSA), and digital rectal examination (DRE). Preliminary data are available from the first 3-5 y of planned observation. The results show declining rates of detection for each succeeding examination. Cancer detection rates are highly dependent on age. The positive predictive value of a solitary examination is low regardless of modality, but any combination of positive results has a much better predictive value. The cancers detected were predominantly clinically localized tumors, and detection of advanced stage cancer was uncommon after the initial examination. Radical prostatectomy was the most common form of treatment. These findings have implications for prostate cancer early detection guidelines and practice.

Aged↗

Awareness of heightened breast cancer risk among first-degree relatives of recently diagnosed breast cancer patients. The High Risk Breast Cancer Consortium.

This investigation had two goals: (a) to determine the proportion of first-degree relatives of recently diagnosed breast cancer patients who are unaware of their elevated risk for breast cancer; and (b) to identify demographic medical, and lifestyle factors that characterize these women. The ultimate objective was to identify women at increased risk who could benefit from breast cancer risk education. Three hundred ninety-five female first-degree relatives, ages 30-75 years, completed a structured telephone interview. Twenty-five % of these women believed that their risk for breast cancer was the "same as or lower than" women who do not have a family history of breast cancer, despite the fact that they had an objectively increased risk. Bivariate analyses revealed that women who were unmarried (chi2 = 14.8; P = 0.001) and had less than or equal to a high school education (chi2 = 9.2; P = 0.002) were significantly less likely to perceive themselves as being at increased risk for breast cancer. In addition, almost one-half of African-American women were unaware of their increased risk compared to only 19% of white women (chi2 = 29.9; P < 0.001). More smokers were unaware of their elevated risk compared to nonsmokers (43 versus 21%; chi2 = 15.1; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Large-scale randomized prostate cancer screening trials: program performances in the European Randomized Screening for Prostate Cancer trial and the Prostate, Lung, Colorectal and Ovary cancer trial.

Two large-scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate-specific antigen (PSA). The PLCO trial and some European centers use also digital rectal examination (DRE) as an ancillary screening test. In the core age group (55-69 years), 3,362 of 32,486 men screened (10%) had a serum PSA concentration of 4 ng/ml or greater, which is 1 cut-off for biopsy (performed in 84%). An additional 6% was referred for further assessment based on other criteria, with much less efficiency. Differences in PSA by country are largely attributable to the age structure of the study population. The mean age-specific PSA levels are lower in the PLCO trial (1.64 ng/ml [in the age group 55-59 years], 1.80 [60-64 years] and 2.18 [65-69 years) than in the ERSPC trial (1.28-1.71 [55-59], 1.75-2.87 [60-64] and 2.48-3.06 [65-69 years]). Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures. In centers with consent to randomization design, adherence in the screening arm is 91%, but less than half of the men in the target population are enrolled in the trial. In population-based centers in which men were randomized prior to consent, all eligible subjects are enrolled, but only about two-thirds of the men in the intervention arm undergo screening. Considerable progress has been made in both trials. Enrollment will be completed in 2001. A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005-2008.

Aged↗