The Global Burden of Disease 2000 (GBD 2000) study deals with the problem of systemic bias in cause-specific mortality by estimating total mortality for each Member State, starting from an analysis of the overall mortality envelope for each region, in order to ensure that the cause-specific estimates add to the total all cause mortality by age and sex and that there is not systematic over- or under- estimation or double counting of deaths. This regional cause-specific mortality envelope serves as an upper bond of mortality from a certain cause and partly ensures the internal consistency among incidence, prevalence and mortality rates 6. The approaches to estimating mortality and incidence of cancer by site also follows this process (Figure 1).

Firstly, we obtained the age- and sex- specific mortality envelope for all malignancies by region derived from the analysis of country life-tables and cause of death models in each region. Secondly, we estimated the site-specific cancer mortality distributions from vital records or cancer survival models depending on the availability and quality of detailed cause of death data. Cancer sites for which survival was calculated were: mouth and pharynx (ICD-10 C00-C14), oesophagus (C15), stomach (C16), colon and rectum (C18-C21), liver (C22), pancreas (C25), trachea, bronchus and lung (C33-C34), melanoma (C43), female breast (C50), cervix uterine (C53), corpus uteri (C54-55), ovary (C56), prostate (C61), bladder (C67), lymphomas and multiple myeloma (C81-C90, C96), leukaemia (C91-C95), and other malignant neoplasms (balance of ICD-10 C00-C97). The GBD 2000 assigns Kaposi's sarcoma and non-Hodgkin lymphomas (NHL) attributable to HIV/AIDS among AIDS sequela and their burden is included separately with HIV/AIDS. Thirdly, the final regional cancer mortality by site is estimated by disaggregating the regional cancer envelope based on the mortality distribution by site. Finally, we applied the incidence-to-mortality rate ratios to back calculate the final cancer incidence estimates by site.

Complete or incomplete vital registration data together with sample registration systems now cover 74% of global mortality in 128 countries. Survey data and indirect demographic techniques provide information on levels of child and adult mortality for the remaining 26% of estimated global mortality. The available sources of mortality data for the WHO sub regions of the GBD 2000 are summarised in Table 1.

Causes of death for the WHO sub regions and the world have been estimated based on data from national vital registration systems that capture about 17 million deaths annually. In addition, information from sample registration systems, population laboratories and epidemiological analyses of specific conditions have been used to improve estimates of the cause of death patterns 689. As a general rule, vital registration data, suitably corrected for ill-defined coding and probable systematic biases in certifying deaths to non-specific vascular, cancer and injury codes were used to estimate the cause of death pattern. The GBD 2000 approach adjusts the cause-specific mortality to include a proportion of deaths coded to ill-defined causes in vital registration data and redistributes these deaths pro-rata among broader communicable and non-communicable causes.

Cause of death data have been carefully analysed to take into account incomplete coverage of vital registration in countries and the likely differences in cause of death patterns that would be expected in the uncovered and often poorer sub-populations 10. For countries lacking sufficient vital registration data, cause of death models were used to firstly estimate the maximum likelihood distribution of deaths across the broad categories of communicable, non-communicable and injuries, based on estimated total mortality rates and income 8. A regional model pattern of specific causes of death was then constructed based on local vital registration and verbal autopsy data, and this proportionate distribution was then applied within each broad cause group. Finally, the resulting estimates were then adjusted based on other epidemiological evidence from specific disease studies. Methods used to estimate global all-cause and cause-specific mortality from these data are described elsewhere 6.

In the GBD 1990 5, deaths coded to ICD-9 195–199 (i.e., malignant neoplasm of other and unspecified sites including those whose point of origin cannot be determined, secondary and unspecified neoplasm) were redistributed pro-rata across all malignant neoplasm categories within each age-sex group, so that the category 'Other malignant neoplasms' includes only malignant neoplasms of other specified sites. Reviews of the cancer registry and methods of diagnosis suggest that four sites (month and pharynx, liver, breast and cervix uteri) where there did not appear to be any significant mis-coding of cancer deaths, since these can be diagnosed clinically without any further diagnostic tests even in developing regions 11. Accordingly, the cancer garbage code redistribution algorithm was revised for the GBD 2000 to redistribute cancer deaths in ICD C76-C80 pro-rata across the sites other than the four sites above.

Given the regional cancer mortality envelope by age and sex, the site-specific distributions of cancer mortality are necessary to disagreggate the estimated total cancer deaths by age and sex for each region. The approaches to estimating mortality distributions were different depending on the availability and quality of data on detailed causes of death.

Direct estimates of the site-specific distributions of cancer mortality were possible for the regions where established vital registration records with high coverage and ICD-coding are available, including countries in the A sub regions (AmrA, EurA and WprA) and countries in AmrB, EurB1, EurB2 and EurC 6. For the other regions of the world (AfrD, AfrE, AmrD, EmrB, EmrD, SearB, SearD, WprB1, WprB2 and WprB3 sub regions), a site-specific model for relative interval survival adjusted for each region was developed and applied to the regional incidence estimated by International Agency for Research on Cancer (IARC) to calculate the mortality distribution by site for the year 2000 712. The region-specific incidence estimates of the Globocan 2000 was adjusted to ensure the consistency with the GBD 2000 definitions 7. Our survival model and adjusted incidence estimates of the Globocan 2000 were primarily used to estimate the distribution, but not the magnitude, of cancer by site, sex, and age group.

The final site-specific cancer mortality was then estimated by multiplying age- and sex- specific regional cancer mortality envelope by estimated cancer mortality distribution by site. The cancer survival model is flexible enough to yield the survival estimates of various age, years and period as well as mean duration of time of cancer by site 7. We estimated incidence-to-mortality rate ratios at each age group form the survival model and, by using the final cancer mortality, applied the ratios to back calculate the final incidence by age and sex for each cancer site in all regions of the world for the year 2000.

The GBD 2000 classifies the cause of deaths into three broad categories: communicable disease, non-communicable disease, and injuries. In 2000, approximately 56 million deaths occurred world wide and non-communicable disease accounted for 58% of total number of deaths, followed by communicable disease (33%) and injuries (9%) (Figure 2). Cancer was estimated to account for over 7 million deaths (13% of total mortality and 22% of non-communicable disease mortality) world wide in 2000, only preceded by cardiovascular diseases (29 % of total) and infectious and parasitic diseases (19%). Depending on the extent of health transition, cancer mortality as a proportion of total mortality differed substantially by region, from less than 5% in AfrE to approximately 30% in WprA sub region.

Tables 2,3,4,5 show the regional estimates of total number of deaths and age-specific mortality rates of all cancers for the GBD 2000. More than 60% of cancer deaths occurred in developing regions, particularly in SearD (mainly India) and WprB1(mainly China) sub regions due to their large population size. On average global cancer mortality rates among males and females were 128.2 and 104.6 per 100,000, respectively. Not surprisingly crude mortality rates from all cancers vary significantly and are much higher in developed regions (AmrA, EurA, and WprA). However, since age-specific mortality rate is generally higher in developing regions, regional mortality rates, age-standardised to the world population, showed less variations compared to crude mortality rates and higher mortality rates were observed in regions such as AfrD, AfrE, AmrB, EurC, and WprB (Figure 3).