N-acetyltransferase 2 (NAT2) metabolizes arylamines and hydrazines moeities found in many therapeutic drugs, chemicals and carcinogens. The gene encoding NAT2 is polymorphic, thus resulting in rapid or slow acetylator phenotypes. The acetylator status may, therefore, predispose drug-induced toxicities and cancer risks, such as bladder, colon and lung cancer. Indeed, some studies demonstrate a positive association between NAT2 rapid acetylator phenotype and colon cancer, but results are inconsistent. The role of NAT2 acetylation status in lung cancer is likewise unclear, in which both the rapid and slow acetylator genotypes have been associated with disease.

Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on survival in patients with lung cancer. Studies evaluating the survival impact of COX-2 in lung cancer, published until December 2005, were selected. Data for estimation of individual hazard ratios (HR) for survival were extracted from the publications and combined in a pooled HR. Among 14 eligible papers, all dealing with non-small-cell lung cancer, 10 provided results for meta-analysis of survival data (evaluable studies). Cyclooxygenase-2 positivity was associated with reduced survival, improved survival or no statistically significant impact in six, one and seven studies, respectively. Combined HR for the 10 evaluable studies (1236 patients) was 1.39 (95% confidence intervals (CI): 0.97-1.99). In stage I lung cancer (six evaluable studies, 554 patients), it was 1.64 (95% CI: 1.21-2.24). No significant impact was shown in ADC. A slight detrimental effect on survival in patients with lung cancer is associated with COX-2 expression, but the statistical significance is not reached. This effect is statistically significant in stage I, suggesting that COX-2 expression could be useful at early stages to distinguish those with a worse prognosis.

Individuals and families dealing with the possibility of hereditary cancer risk face numerous decisions, including whether to obtain genetic testing. The purpose of this article is to determine what is known about the rate at which people obtain cancer genetic testing.

Polymorphisms in the vitamin D receptor gene have been hypothesized to alter the risk of prostate cancer. However, studies investigating the associations between specific vitamin D receptor polymorphisms and prostate cancer risk have yielded inconsistent results.

Microsomal epoxide hydrolase 1 (EPHX1) plays an important role in both the activation and detoxification of tobacco-derived carcinogens. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to review and summarize the available molecular epidemiologic studies of lung cancer and EPHX1.

The incidence of oesophageal adenocarcinoma is increasing in the UK faster than any other malignancy. Despite its relatively poor prognosis and the limited success of existing treatments, there is enthusiasm that chemopreventive agents might be able to stem the transition from normal squamous epithelium to adenocarcinoma. We discuss gastro-oesophageal reflux as the main risk factor for the development of Barrett's metaplasia, the only known precursor of oesophageal adenocarcinoma. Treatment options for reflux disease are considered with regard to their effects on cancer risk. Recent advances in the molecular and cell biology of Barrett's are outlined, and potential targets for chemoprevention examined. Available treatments for reflux disease have not convincingly altered the likelihood of cancer development. Epidemiological and animal studies support the use of non-steroidal anti-inflammatory drugs as potential chemopreventive agents. Dietary agents, however, have a more favourable side-effect profile and may prove to be an attractive alternative, although more work is needed to fully explore this prospect.

This review will discuss the discovery and development of RNA interference (RNAi) technology, small interfering RNA (siRNA) design and delivery, and the implications of RNAi on gynecologic cancers.

We performed a systematic review of 28 case-control, 17 cohort and seven twin studies of the relationship between family history and risk of lung cancer and a meta-analysis of risk estimates. Data from both case-control and cohort studies show a significantly increased lung cancer risk associated with having an affected relative. Risk appears to be greater in relatives of cases diagnosed at a young age and in those with multiple affected family members. Increased lung cancer risk was observed in association with an affected spouse and twin studies, while limited, favour shared environmental exposures. The limitations of the currently published epidemiological studies to infer genetic susceptibility are discussed.

Clinically significant mutations of BRCA1 and BRCA2 genes are associated with increased susceptibility for breast and ovarian cancer. Although these mutations are uncommon, public interest in testing for them is growing.

Results from studies investigating the relationship between colorectal cancer survival and chromosome 18q allelic imbalance (AI)/loss of DCC expression (LOE) have been inconsistent. We have reviewed and pooled published studies to estimate the prognostic significance of chromosome 18q status more precisely. Data from 27 studies were eligible. Survival data were pooled using standard meta-analysis techniques. Considerable variation between assessment method, marker choice, and threshold for assigning AI/LOE was observed. Pooling data from a 2189 cases from 17 studies showed significantly worse overall survival in patients with AI/LOE (HR = 2.00, 95%CI: 1.49-2.69), maintained both in the adjuvant setting (HR = 1.69, 95%CI:1.13-2.54), and also by method (HR = 1.67, 95%CI: 1.19-2.36, genotyping microsatellites; HR = 3.00, 95%CI: 1.98-4.56, immunohistochemistry). There was however evidence of heterogeneity and publication bias. Cancers with chromosome 18q loss appear to have a poorer prognosis. Prospective studies using consistent methodology are needed to precisely quantify its effect and role in patients with stage II-III disease.

Despite numerous individual studies of psychological factors (depression, anxiety, distress) related to genetic testing for inherited cancer syndromes (CGT), there has been no systematic review of the psychological factors are measured among individuals at increased risk for hereditary breast, ovarian, or colon cancer. Our review provides an analysis of psychological factors in studies of CGT and discusses the instruments most commonly used to measure them. We performed a literature search using three major OVID databases from 1993 to January 2003. In the 19 studies that met our inclusion criteria, the most commonly assessed psychological factors were distress, anxiety, and depression. These factors were most often measured by the impact of event scale (IES), the state-trait anxiety inventory (STAI), and the Centers for Epidemiologic Studies and Depression scale (CES-D), respectively. Our results show deficits in the existing body of literature on psychological factors associated with CGT including limited documentation of psychometrics and variability in instrumentation.

Glutathione s-transferase (GST) polymorphisms (GSTM1, GSTP1 and GSTT1) have been considered as risk factors for developing acute leukaemia in a number of studies; however the overall results of such studies are inconsistent. To investigate a putative association of GST polymorphisms with the risk of acute leukaemia, we performed a systematic review and meta-analysis of 30 published case-control studies. To take into account the possibility of heterogeneity across the studies, a statistical test was performed. The pooled odds ratios (ORs) were assessed using both a fixed-effects and a random-effects model. The pooled OR of acute leukaemia risks associated with GSTM1 null genotype, GSTP1 Val105 allele and GSTT1 null genotype were 1.22 (95% confidence interval (CI) 1.07-1.38), 1.07 (95% CI 1.00-1.13) and 1.19 (95% CI 1.00-1.41), respectively. Significantly increased risk of acute lymphoblastic leukaemia associated with GSTM1 and GSTT1 null genotypes was observed. Their pooled ORs were 1.24 (95% CI 1.17-1.31) and 1.30 (95% CI 1.06-1.60), respectively. We also found substantial evidence of heterogeneity between the studies. Our results suggest that GSTM1 and GSTT1, but not GSTP1 polymorphisms, appear to be associated with a modest increase in the risk of acute lymphoblastic leukaemia. It is conceivable that GSTM1 and GSTT1 null genotypes may thus play a role in leukemogenesis. A review of the 30 case-control studies indicates that greater attention should be paid to the design of future studies.

The objective of this study was to conduct a broad-based systematic review of social, ethical, and legal considerations associated with genetic cancer risk assessment technologies (CaRATs). This paper focuses on psychosocial and ethical issues. Search results were limited to papers published in English, French, or German from January, 1990, to May, 2003. A quality assessment tool was developed and applied to retrieved papers. Application of the quality assessment tool resulted in 77 of 247 qualitative and quantitative primary research papers being reviewed and synthesized. A broad range of issues were addressed and grouped into content areas. Despite a large literature addressing psychosocial and ethical issues associated with CaRATs, many existing studies are not adequate to inform decision-makers and stakeholders. Careful policy analysis, as in some of the economic analyses reviewed here, is important to bridge this gap.

Phase I/II enzymes metabolize environmental carcin-ogens and several functional polymorphisms have been reported in their encoding genes. Although their significance with regard to esophageal carcinogenicity has been examined epidemiologically, it remains controversial. The present systematic review of the literature was performed to clarify associations.

Although differences in prostate cancer incidence and mortality between black and white men are widely accepted, the existence of racial differences in treatment outcomes remains controversial. We conducted a systematic review of racial differences in prostate cancer treatment outcomes. Systematic review of literature from 1992-2002 was conducted. Database searches were performed using the terms: "prostate cancer" (keyword) or "prostate neoplasm" (subject heading) + "blacks" (subject heading) or "blacks" (keyword) + "African-Americans" (subject heading or "African-Americans" (keyword). Two hundred fifty-eight relevant articles were identified; 29 fit the inclusion criteria. All but 3 were retrospective. Seven (24%) studies were conducted at Veterans Affairs medical centers. Treatment included radical prostatectomy (15 studies), hormonal therapy (5 studies), and radiotherapy (12 studies). Three studies included more than 1 treatment. Twenty-three (79%) studies, observed no significant difference in treatment outcomes between races. The remainder found worse outcomes among black men, including worse 5-year survival (HR range, 2.35-96.74) and higher rates of PSA failure (OR range, 1.15-1.69). Most studies investigating racial differences in prostate cancer treatment outcomes over the past 10 years found no difference between races after controlling for tumor and patient characteristics. Efforts to narrow the gap between black and white prostate cancer mortality should focus on ensuring that all patients receive optimal treatment and that all patients become informed about the use of screening for early cancer detection. Research should focus on interventions to reduce advanced presentation of the disease and disease-related mortality among black men.

This systematic review aims to assess the psychological impact of mammographic screening on women with a family history of breast cancer. Women with a family history, and hence increased risk, of breast cancer are known to experience higher levels of anxiety about cancer. They are also often offered screening from an earlier age. The psychological consequences of screening are therefore of particular importance for this group of women. A comprehensive search of 4 electronic databases was conducted from 1982 to 2003, combining sets of terms relating to (1) breast screening or mammography (breast screen*; mammogra*), (2) psychological impact (adverse effects; anxi*; distress; nervous; psych*, psychological consequences; stress; worry) and (3) family history. Reference lists from relevant papers were examined for additional papers. The review identified seven papers from four countries. Overall, the findings indicate that, similar to women in the general population, most women with a family history do not appear to experience high levels of anxiety associated with mammographic screening. Although women who are recalled for further tests do experience increased anxiety the levels appear to be no greater than for women without a family history. We conclude that further research on this topic is required--this should include studies designed specifically to consider both the negative and positive impact of mammographic screening on women with a family history, using validated measures of anxiety and worry in combination with qualitative research.

Uterine leiomyomas are extremely common and a major cause of pelvic pain, bleeding, infertility, and the leading indication for hysterectomy. Familial and epidemiological studies provide compelling evidence that genetic alterations play an important role in leiomyoma development.

We performed a systematic review of studies that investigated the effect of abnormalities of the tumour suppressor gene p53 upon prognosis in patients with colorectal cancer. The methods used to assess p53 status were immunohistochemistry (IHC), indicating abnormal accumulation of p53, and sequence analysis, indicating presence of p53 mutations (mut). We identified 168 reports, with 241 comparisons of relevant end points and survival data on 18 766 patients. We found evidence of both publication bias and heterogeneity of results. Our analysis was hampered by variability in both the assessment of p53 status and the reporting of results. We used a trim and fill method to correct for publication bias and minimised heterogeneity by using well-defined clinical subgroups for the assessment of outcomes. Overall, patients with abnormal p53 were at increased risk of death: relative risk (RR) with IHC 1.32 (95% confidence interval (c.i.) 1.23-1.42) and with mutation analysis 1.31 (95% c.i. 1.19-1.45). The adverse impact of abnormal p53 was greater in patients with lower baseline risk of dying: good prognosis RR (mut) 1.63 (95% c.i. 1.40-1.90) and poor prognosis RR (mut) 1.04 (95% c.i. 0.91-1.19). We found no effect of abnormal p53 on outcome in patients treated with chemotherapy. Abnormal p53 was associated with failure of response to radiotherapy in patients with rectal cancer: RR (mut) 1.49 (95% c.i. 1.25-1.77).

We reviewed all English-language articles on associations among circulating levels of the insulin-like growth factors (IGF) and their binding proteins (IGFBP), polymorphisms in their genes, and breast cancer risk. In premenopausal women, five of eight IGF-I studies and four of six IGFBP-3 studies of circulating levels found that women in the highest quantile had more than twice the risk of developing breast cancer of those in the lowest, although in some this effect was only apparent at young ages. In postmenopausal women, however, there was no consistent effect. A simple sequence length polymorphism 1 kb 5' to IGF-I was examined in relation to circulating levels of IGF-I (12 studies) or breast cancer risk (4 studies), but there was no convincing evidence of any effect. For an A/C polymorphism 5' to IGFBP-3, all three studies were consistent with a modest effect on circulating levels, but no evidence of a direct effect on breast cancer risk was seen in the only relevant study. Variation within the reference range of IGF-I and IGFBP-3 may confer only modest increases in breast cancer risk, and any single polymorphism may only account for a small proportion of that variation. Nevertheless, population attributable fractions for high circulating levels of IGF-I and IGFBP-3 and for common genetic variants could be substantial. Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely.

A number of studies have investigated the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Although many have reported a better survival with MSI, estimates of the hazard ratio (HR) among studies differ. To derive a more precise estimate of the prognostic significance of MSI, we have reviewed and pooled data from published studies.