To determine whether blacks with hormone-refractory prostate cancer have shorter survival compared with whites with the same disease.

The L-myc EcoRI polymorphism is a noncoding variation in the second intron of the L-myc gene, resulting in S and L alleles. Individuals carrying the S allele tend to have poor prognosis and increased risk of several tumor types, although controversial results have been reported. A meta-analysis of 36 studies on L-myc EcoRI genotyping, including 3563 patients with different types of cancer and 2953 controls, was performed. In lung cancer patients the S/S genotype was significantly associated with lymph node metastasis [odds ratio (OR), 2.8; 95% confidence interval (CI), 1.8-4.3], distant metastasis (OR, 4.7; 95% CI, 2.4-9.2), and stage (OR, 2.3; 95% CI, 1.2-4.4). No association was observed between the S/S genotype and cancer (OR, 1.1; 95% CI, 0.8-1.4). In patients with other cancers, the S/S genotype was significantly associated with tumor recurrence (OR, 2.8; 95% CI, 1.4-6.0), whereas no significant association was seen for the other prognostic parameters. When all types of cancer were examined together, the S/S genotype was associated with lymph node metastasis (OR, 2.3; 95% CI, 1.6-3.3), distant metastasis (OR, 2.9; 95% CI, 1.8-4.6), clinical stage (OR, 1.8; 95% CI, 1.2-2.9), and cancer risk (OR, 1.25; 95% CI, 1.07-1.45). The meta-analysis suggests that the L-myc EcoRI polymorphism is a marker of tumor prognosis in lung cancer and possibly in other types of cancer.

A major focus of current cancer research is to identify genes that can be used as markers for prognosis and diagnosis, and as targets for therapy. Microarray technology has been applied extensively for this purpose, even though it has been reported that the agreement between microarray platforms is poor. A critical question is: how can we best combine the measurements of matched genes across microarray platforms to develop diagnostic and prognostic tools related to the underlying biology?

Many studies have used DNA microarrays to identify the gene expression signatures of human cancer, yet the critical features of these often unmanageably large signatures remain elusive. To address this, we developed a statistical method, comparative metaprofiling, which identifies and assesses the intersection of multiple gene expression signatures from a diverse collection of microarray data sets. We collected and analyzed 40 published cancer microarray data sets, comprising 38 million gene expression measurements from >3,700 cancer samples. From this, we characterized a common transcriptional profile that is universally activated in most cancer types relative to the normal tissues from which they arose, likely reflecting essential transcriptional features of neoplastic transformation. In addition, we characterized a transcriptional profile that is commonly activated in various types of undifferentiated cancer, suggesting common molecular mechanisms by which cancer cells progress and avoid differentiation. Finally, we validated these transcriptional profiles on independent data sets.

Although some studies have reported that the arginine isoform on codon 72 of p53 increases the susceptibility to invasive cervical cancer, such data remain controversial. The objective of this study was to quantitatively summarize the evidence for such a relationship.

Our aim was to analyze the clinicopathologic features of screen-detected ovarian cancers identified in women, either at general population risk or high genetic risk of ovarian cancer, who have participated in screening studies.

Given that there are millions of single-nucleotide polymorphisms (SNPs) in the entire human genome, a major difficulty faced by scientists in planning costly population-based genotyping is to choose target SNPs that are most likely to affect phenotypic functions and ultimately contribute to disease development. Although it is widely accepted that sequences with important functionality tend to be less variable across species because of selective pressure, to what extent evolutionary conservation is mirrored by epidemiological outcome has never been demonstrated. In this study, we surveyed odds ratios detected for 46 SNPs in 39 different cancer-related genes from 166 molecular epidemiological studies. The conservation levels of amino acid that these SNPs affected were calculated as a tolerance index by comparing sequences from different species. Our results provide evidence of a significant relationship between the detected odds ratios associated with cancer risk and the conservation levels of the SNP-affected amino acids (P = 0.002; R(2) = 0.06). Tolerance indices were further calculated for 355 nonsynonymous SNPs identified in 90 human DNA repair genes, of which 103 caused amino acid changes in very conserved positions. Our findings support the concept that SNPs altering the conserved amino acids are more likely to be associated with cancer susceptibility. Using such a molecular evolutionary approach may hold great promise for prioritizing SNPs to be genotyped in future molecular epidemiological studies.

Present guidelines to identify hereditary non-polyposis colorectal cancer (HNPCC) families are criticized for limitations in accuracy. The Amsterdam criteria I and II (AC I and AC II) are used to predict a germline mutation in one of the mismatch repair genes. In families not fulfilling the AC I and AC II criteria, individual indications to test cancer specimens for microsatellite instability (MSI) are guided by the Bethesda Guidelines (BG). Germline mutation testing is then performed in patients who conform to the BG and show MSI. We investigated the sensitivity and specificity of AC I, AC II, and BG. A meta-analysis of studies on the value of the AC I and AC II criteria for predicting germline mutation, as well as a meta-analysis of BG for the detection of MSI was performed. For the AC I, sensitivity varied from 54 to 91% and specificity varied from 62 to 84%. For the AC II, the pooled sensitivity was 78% and specificity ranged between 46 and 68%. Post-test probabilities of a positive test result were 0.61 and 0.46 for the AC I and AC II, respectively. Post-test probabilities of a negative test result were 0.17 and 0.21 for the AC I and AC II, respectively. For the BG, the pooled sensitivity was 89% and pooled specificity was 53%. Post-test probability of a positive test result was 41%, and post-test probability of a negative test result was 9%. The sensitivity and specificity of the Amsterdam criteria for predicting a germline mutation that causes HNPCC is not sufficient. The BG are useful for the detection of MSI in a group of patients suspected of having familial colorectal cancer (CRC), but sensitivity is very low in the total group of newly diagnosed CRC patients. Therefore, a new strategy is needed for the identification of HNPCC.

We studied the relation of breast cancer to common deletion mutations in GSTM1 and GSTT1 and the functional Ile(105)Val polymorphism in GSTP1 in a large, population-based case-control study conducted in China and performed a meta-analysis to summarize the literature.

The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated as a risk marker in cervical neoplasia. However, research on this topic has produced controversial results. We reviewed the published literature to summarize the association and to identify methodological features that may have contributed to the heterogeneity. Information on specific methodological features of studies addressing this topic published between 1998 and 2002 were obtained. Study-specific odds ratios (ORs) were combined in a meta-analysis, assuming random effects. To identify characteristics that significantly contributed to heterogeneity, we used meta-regression analysis. We identified 50 articles, of which 45 were included in the meta-analyses and regressions. No evidence of association or heterogeneity was detected for preinvasive lesions. For invasive cervical cancer with undefined histology, the Arg/Arg genotype was not found to affect risk (OR, 1.1; 95% confidence interval (CI), 0.9-1.3). However, a slightly increased risk was observed for squamous cell carcinoma (OR, 1.5; 95% CI, 1.2-1.9) and adenocarcinoma (OR, 1.7; 95% CI, 1.0-2.7). Meta-regression analysis identified that the most important factor contributing to heterogeneity among results for invasive lesions was departures from Hardy-Weinberg equilibrium in the control group. Summary ORs for studies in equilibrium were essentially null. A possible susceptibility role by the p53 codon 72 polymorphism at a late carcinogenetic stage in cervical cancer cannot be ruled out. However, various methodological features can contribute to departures from Hardy-Weinberg equilibrium and consequently to less than ideal circumstances for the examination of this polymorphism. Future investigations require appropriate attention to design and methodological issues.

Identification of a genetic basis underlying certain types of cancer has led to an increase in demand for genetic counseling about individual risks of the disease. We conducted a systematic review of the literature to determine the quality and strength of evidence relating to psychological outcomes of genetic counseling for familial cancer.

Sequence variation in the GSTM1, GSTT1, GSTP1, and CYP1A1 genes may potentially alter susceptibility to head and neck cancers, although evidence from previous studies has not been consistent. To explore these associations, we conducted a meta-analysis of 31 published case-control studies (4635 cases and 5770 controls) and a pooled analysis of original data from nine published and two unpublished case-control studies (2334 cases and 2766 controls). In the meta-analysis, the summary odds ratios (ORs) for head and neck cancer were 1.23 [95% confidence interval (95% CI), 1.06-1.42] for the GSTM1 null genotype, 1.17 (95% CI, 0.98-1.40) for the GSTT1 null genotype, 1.10 (95% CI, 0.92-1.31) for carrying the GSTP1 Val105 allele, and 1.35 (95% CI, 0.95-1.82) for carrying the CYP1A1 Val462 allele. The pooled analysis ORs were 1.32 (95% CI, 1.07-1.62) for the GSTM1 null genotype, 1.25 (95% CI, 1.00-1.57) for the GSTT1 null genotype, 1.15 (95% CI, 0.86-1.53) for carrying the GSTP1 Val105 allele, and 0.98 (95% CI, 0.75-1.29) for carrying the CYP1A1 Val462 allele. Increasing risk of head and neck cancer was observed with inheritance of increasing numbers of modest risk genotypes at the three GST loci (P for trend = 0.04), with the combination of carrying the GSTM1 null, GSTT1 null, and GSTP1 Val105 alleles conferring an OR of 2.06 (95% CI, 1.11-3.81). In conclusion, both the meta- and pooled analysis support modest associations of GSTM1 and GSTT1 genotypes with head and neck cancer risk, and our pooled analysis supports the notion of greater risk when genotypes at multiple GST loci are considered in a multigenic model.

Several polymorphisms in the vitamin D receptor (VDR) gene have been implicated as risk factors for prostate cancer. We performed a meta-analysis of 14 studies (17 comparisons) with TaqI genotyping (1870 prostate cancer cases; 2843 controls), 6 studies (8 comparisons) with poly(A) repeat genotyping (540 cases; 870 controls), 5 studies with BsmI genotyping (987 cases; 1504 controls), and 3 studies with FokI genotyping (514 cases; 545 controls). The random-effects odds ratio (OR) for the t versus T allele was 0.95 [95% confidence interval (CI), 0.86-1.05]. There was no suggestion of an overall effect either in recessive or dominant modeling, and the comparison of t/t versus T/T also showed no differential prostate cancer susceptibility (OR, 0.88; 95% CI, 0.70-1.10). No effect of t was seen in subjects of European descent (nine comparisons; OR, 0.97; 95% CI, 0.87-1.08), Asian descent (five comparisons; OR, 0.88; 95% CI, 0.66-1.17), or African descent (three comparisons; OR, 0.94; 95% CI, 0.41-2.17). There was no between-study heterogeneity in any of these analyses. Overall, the random effects OR was 0.94 (95% CI, 0.75-1.18; no between-study heterogeneity) for the S versus L allele, 0.92 (95% CI, 0.63-1.35; P < 0.01 for heterogeneity) for the B versus b allele, and 1.03 (95% CI, 0.86-1.23; no between-study heterogeneity) for the f versus F allele. The meta-analysis shows that these four polymorphisms are unlikely to be major determinants of susceptibility to prostate cancer on a wide population basis.

Anthracyclines have been incorporated into adjuvant chemotherapy regimens for breast cancer since the 1980s. A metaanalysis confirmed that regimens containing anthracyclines result in better disease-free and overall survival than standard CMF (cyclophosphamide/methotrexate/5-fluorouracil), with a proportional reduction of 11% in risk of death at 10 years with the addition of these agents. Dose escalation of doxorubicin results in outcome improvement up to a threshold dose beyond which no further improvement is seen. Epirubicin, with its better toxicity profile, can be escalated to higher doses than doxorubicin, with better outcomes associated with higher dose levels. Tumors expressing HER2/neu may respond better to anthracycline-containing regimens than to standard CMF, but this remains controversial. Newer regimens combining anthracyclines with taxanes may offer a slight additional advantage in terms of disease-free and overall survival in some patient populations. The scheduling of treatment is important, with recent results of dose-dense scheduling showing a greater survival benefit than conventional scheduling. Ongoing clinical trials should further define the best choice of anthracycline and the optimal dose and schedule of treatment.

An increased risk of prostate cancer associated with a family history of prostate cancer has been documented in multiple published reports. Risk has been shown to vary by degree of relationship and age of onset of disease in the affected relative. Several studies, using various designs, have estimated the relative risk (RR) for these associations. The purpose of our study was to identify and summarize published reports on the relationship between risk of prostate cancer and family history, which is defined as having a father, brother, any first- or second-degree relative or other relative affected with prostate cancer. A Medline and manual search from 1982 to 2000 identified 24 studies that reported RR and confidence intervals (CI) and satisfied inclusion criteria. Pooled RR estimates based upon a weighted average model were as follows: any affected family member RR = 1.93, CI 1.65-2.26; affected first-degree relative RR = 2.22, CI 2.06-2.40; affected second-degree relative RR = 1.88, CI 1.54-2.30; father with prostate cancer RR = 2.12, CI 1.82-2.51; and brother with prostate cancer RR = 2.87, CI 2.21-3.73). Statistical comparison of pooled data demonstrated that the RR is significantly higher for affected brother than for affected father (p < 0.03). A sensitivity analysis demonstrated that these results are robust with respect to population bias. This meta-analysis confirms that risk of prostate cancer is associated with family history of disease and improves the quantification of this risk.

Glutathione S-transferase M1 is an important phase II enzyme involved in the detoxification of many environmental carcinogens. It has been postulated that individuals with GSTM1 deficiency have increased susceptibility to carcinogens and are more likely to develop cancer. GSTM1 status has been extensively studied as a colon cancer risk factor, although published studies have produced conflicting results. To re-examine this controversy, we have undertaken a meta-analysis investigating the relationship of GSTM1 status and colon cancer risk.

To comprehensively analyse and evaluate the risk factors and to predict the trend of breast cancer in China.