Colorectal cancer survival in the USA and Europe: a CONCORD high-resolution study.

OBJECTIVES: To assess the extent to which stage at diagnosis and adherence to treatment guidelines may explain the persistent differences in colorectal cancer survival between the USA and Europe. DESIGN: A high-resolution study using detailed clinical data on Dukes' stage, diagnostic procedures, treatment and follow-up, collected directly from medical records by trained abstractors under a single protocol, with standardised quality control and central statistical analysis. SETTING AND PARTICIPANTS: 21 population-based registries in seven US states and nine European countries provided data for random samples comprising 12 523 adults (15-99 years) diagnosed with colorectal cancer during 1996-1998. OUTCOME MEASURES: Logistic regression models were used to compare adherence to 'standard care' in the USA and Europe. Net survival and excess risk of death were estimated with flexible parametric models. RESULTS: The proportion of Dukes' A and B tumours was similar in the USA and Europe, while that of Dukes' C was more frequent in the USA (38% vs 21%) and of Dukes' D more frequent in Europe (22% vs 10%). Resection with curative intent was more frequent in the USA (85% vs 75%). Elderly patients (75-99 years) were 70-90% less likely to receive radiotherapy and chemotherapy. Age-standardised 5-year net survival was similar in the USA (58%) and Northern and Western Europe (54-56%) and lowest in Eastern Europe (42%). The mean excess hazard up to 5 years after diagnosis was highest in Eastern Europe, especially among elderly patients and those with Dukes' D tumours. CONCLUSIONS: The wide differences in colorectal cancer survival between Europe and the USA in the late 1990s are probably attributable to earlier stage and more extensive use of surgery and adjuvant treatment in the USA. Elderly patients with colorectal cancer received surgery, chemotherapy or radiotherapy less often than younger patients, despite evidence that they could also have benefited

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Breast cancer survival in the US and Europe: a CONCORD high-resolution study.

Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age-standardized survival. The aim of this study is to explain these survival differences. Population-based data on stage at diagnosis, diagnostic procedures, treatment and follow-up were collected for about 20,000 women diagnosed with breast cancer aged 15-99 years during 1996-98 in 7 US states and 12 European countries. Age-standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node-negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5-6%). Net survival in Northern, Western and Southern Europe (81-84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70-99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Breast cancer disparities in South Carolina: early detection, special programs, and descriptive epidemiology.

A discrepancy exists between mortality and incidence rates between African-American and European-American women in South Carolina. The relationship between tumor grade and the estrogen/ progesterone receptor status is different in African-American and European-American women. African-American women with breast cancer should be encouraged to participate in clinical trials, with the goal of identifying biological factors that might facilitate the detection of tumors at an earlier stage and the development of more effective therapies. The most important of our goals is to design studies to reduce the incidence of the disease and interventions to improve survival and quality of life. The importance of participation in research cannot be overstated. Reproductive factors such as early pregnancy and multiple pregnancies are strongly related to breast cancer risk, however, promotion of these factors as a "prevention strategy," clearly does not lead to cogent, comprehensive public health messages. Data from ecological and migrant studies point clearly to other factors that may be important such as diet. Additional research around primary prevention strategies is needed. In addition, yearly mammograms (secondary prevention) are recommended for women over 50 years old or those with relatives who have developed breast cancer. The Best Chance Network, as a provider of screenings to low-income, uninsured women, has helped to narrow the racial gap in screening that otherwise might exist (see Figures 3 and 4) to a large extent. The determination for timing of surgery after diagnosis needs additional consideration. For example, factors such as effective screening in younger women, timing of screening and surgery in relationship to the ovulatory cycle, and season of screening and surgery may have a great impact on outcomes and may offer some insight into the process of carcinogenesis and therapeutic efficacy. Research into this area is so novel that the impact on possible ethnic disparities is completely unknown. The South Carolina Cancer Disparities Community Network (SCCDCN) has identified the following areas as potential research foci: Identification of small media interventions as an effective strategy to motivate targeted populations, especially those least likely to seek screening for breast cancer and those least likely to participate in research programs (African-Americans). Utilization of breast cancer survivors, self-identified as community natural helpers, can share their experiences with their church congregation. A replication of such a program in South Carolina has great potential because of the strong presence of the church, especially in rural parts of the state. Programs that closely integrate religion with screening women for breast cancer are promising in this state. Development of a mammography registry whereby information on all mammography procedures would be collected within a single database system (much like a central cancer registry). This would aid in identifying population groups that could be targeted for special programs and in the examination and exploration of the most appropriate modalities of detection. Such a resource could also be a useful tool to encourage screening. Thus, this focus area has the potential to benefit epidemiologic and health promotion research on many different levels. Additional breast cancer screening methods should not be overlooked as a potential research focus. Mammography is not the only valid screening method for breast cancer. Magnetic resonance imaging has shown some promise for screening among women with a genetic predisposition for cancer. Another promising avenue is thermography. Because detection rates may depend on age, ethnicity, and breast mammographic characteristics, women for whom regular screening methods do not detect their cancers (e.g. older age, African-American ethnicity, dense breasts) must be identified and other screening methods promoted within these populations. The above-mentioned mammography registry would support this type of research