Freddy Sitas

Association between infection with Helicobacter pylori and risk of gastric cancer : evidence from a prospective investigation

OBJECTIVE--To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN--Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS--29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS--20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS--H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.

The burden of non-communicable diseases in South Africa

15 years after its first democratic election, South Africa is in the midst of a profound health transition that is characterised by a quadruple burden of communicable, non-communicable, perinatal and maternal, and injury-related disorders. Non-communicable diseases are emerging in both rural and urban areas, most prominently in poor people living in urban settings, and are resulting in increasing pressure on acute and chronic health-care services. Major factors include demographic change leading to a rise in the proportion of people older than 60 years, despite the negative effect of HIV/AIDS on life expectancy. The burden of these diseases will probably increase as the roll-out of antiretroviral therapy takes effect and reduces mortality from HIV/AIDS. The scale of the challenge posed by the combined and growing burden of HIV/AIDS and non-communicable diseases demands an extraordinary response that South Africa is well able to provide. Concerted action is needed to strengthen the district-based primary health-care system, to integrate the care of chronic diseases and management of risk factors, to develop a national surveillance system, and to apply interventions of proven cost-effectiveness in the primary and secondary prevention of such diseases within populations and health services. We urge the launching of a national initiative to establish sites of service excellence in urban and rural settings throughout South Africa to trial, assess, and implement integrated care interventions for chronic infectious and non-communicable diseases.

Cohort profile: the 45 and up study.

In common with virtually all industrialized countries and many less developed nations, Australia is facing rapid population ageing. Historical patterns of fertility and migration, along with changes in life expectancy, mean that the over 65 age group is likely to increase by around 50% in the next 15–20 years. The further increase in the proportion of people in the very old age groups will result in the ‘ageing of the aged’. The challenges presented by the ageing of the population are far reaching. Discussions have tended to focus on its likely health and economic consequences; however, few aspects of society will remain unaffected by the issue. There is an urgent need for reliable evidence to inform policy to support healthy ageing. The concept of healthy ageing encompasses traditional ideas relating to freedom from disease, as well as broader considerations including independence, quality of life, management of disability, participation in society and the workforce and productivity. A wide range of factors are likely to affect health in later life, including socioeconomic, environmental and cultural variables, cigarette smoking, alcohol consumption, diet, physical activity, reproductive and hormonal factors, infections, availability of healthcare and use of pharmaceutical agents, as well as individuals’ susceptibility to disease. A comprehensive investigation of the determinants of healthy ageing must incorporate assessment of disease risk, quality of life and other indices, in relation to a very wide range of possible exposures, and with consideration of how these exposures might interact with one another. Research needs to be of a sufficient scale to provide specific information on the major diseases and health problems experienced in later life. This is because reliable assessments of risk factor–disease relationships require a substantial degree of pathological homogeneity of outcome and appropriate consideration of confounding. At the same time, research needs to be able to assess the broad risks and benefits of particular exposures, to allow meaningful conclusions to be reached about suitable public health interventions. Finally, it needs to be large and long term enough to track the impact of health interventions and policies at the population level. Australia has some unique characteristics that will impact on healthy ageing and provide particular challenges in delivering health care. For example, it has: a relatively heterogenous population with a large migrant community; an indigenous population with an average life expectancy 17 years less than for nonindigenous Australians; some remote and sparsely populated regions and a mixed health care system with responsibility shared between the national and state governments and delivery in both the public and private sectors. Excellent population-level databases relating to use of health services and medications, and registers of cancers and deaths, are available for statistical linkage with research data sets. There is therefore a need for research that addresses issues specific to the Australian population and makes use of the unique features of the Australian setting, giving the opportunity to provide insights of international relevance. The 45 and Up Study was conceived as a long-term collaborative resource to investigate healthy ageing, in response to the gaps in existing knowledge and the needs of researchers. Initial discussions among interested researchers resulted in the formation of a Scientific Steering Group in 2003 to oversee the development of the Study. The Study is auspiced by the Sax Institute, which also provided funding for its development. The Sax Institute is an independent organization with core funding from the state government of New South Wales, Australia’s most populous state. Its mission is to improve health through facilitating high-quality research and increasing the impact of this research on health policy and services; it has membership from y The Writing Committee is listed at the end of the report. For a list of the 45 and Up Study Collaborators please go to www.45andUp.org.au.

Part I: Cancer in Indigenous Africans—burden, distribution, and trends

Cancer is an under-emphasised issue in Africa, partly because of the overwhelming burden of communicable diseases. However cancer is a common disease in Africa with 650 000 people, of a population of 965 million, diagnosed annually. Furthermore, the lifetime risk in females (between 0 and 64 years) of cancer is about 10%, which is only about 30% lower than the risk in developed countries. In females, the lifetime risk of dying from cancer in Africa is almost double the risk in developed countries. This Review is the first of two papers and focuses on the current knowledge of the distribution and trends of the most common cancers in Africa. The cancers with the highest incidence are cervical, breast, and now HIV-associated Kaposis sarcoma. The top five cancers in males--Kaposis sarcoma (constituting 12.9% of all cancers in males) and cancer of the liver (14.8%), prostate (9.5%), bladder (6.1%), and non-Hodgkin lymphoma (5.7%)--and in females--cancer of the cervix (constituting 23.3% of all cancers in females) and breast (19.2%), Kaposis sarcoma (5.1%), cancer of the liver (5.0%), and non-Hodgkin lymphoma (3.7%)--are discussed in detail. The second paper will focus on the causes and control of cancer in Africa. The cancer burden in Africa is likely to increase as a result of increases in HIV-associated cancers, changes in lifestyles associated with economic development, and the increasing age of the population (despite AIDS). Although the knowledge of cancer in this region is improving, better surveillance of cancer incidence, mortality, and prevalence of risk factors is urgently needed to monitor the development of the cancer epidemic, formulate appropriate cancer-control strategies, and assess the outcomes of these strategies.

Helicobacter pylori infection rates in relation to age and social class in a population of Welsh men.

The seroprevalence of IgG antibodies to Helicobacter pylori was determined using a standard enzyme linked immunosorbent assay in a population of 749 randomly selected men, aged 30-75 years, from Caerphilly, South Wales. The overall prevalence of H pylori was 56.9%, increasing sharply in middle age from 29.8% in those aged 30-34 to over 59% in those aged 45 or older (p less than 0.0001). Age standardised seroprevalence rates were lowest in combined social class categories I and II (49.2%), intermediate in categories IIIN and M (57.5%), and highest in categories IV and V (62.2%) (p = 0.01). In those aged 30-34 years, the prevalence rate for those in combined social class categories IV and V was 57.9% - double the rate for social class categories IIIM and N (28.3%) and five times the prevalence rate in those in social class categories I and II (11.1%). These differences in the infection patterns of H pylori by social class are consistent with patterns of peptic ulcer disease and gastric cancer.

The spectrum of HIV‐1 related cancers in South Africa

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposis sarcoma (OR=21.9, 95% CI=12.5–38.6), non‐Hodgkin lymphoma (OR=5.0, 95%CI=2.7–9.5), vulval cancer (OR=4.8, 95%CI=1.9–12.2) and cervical cancer (OR=1.6, 95%CI=1.1–2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposis sarcoma, non‐Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposis sarcoma and non‐Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West. Int. J. Cancer 88:489–492, 2000.

Cervical carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies.

The International Collaboration of Epidemiological Studies of Cervical Cancer has combined individual data on 11,161 women with invasive carcinoma, 5,402 women with cervical intraepithelial neoplasia (CIN)3/carcinoma in situ and 33,542 women without cervical carcinoma from 25 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of cervical carcinoma in relation to number of full‐term pregnancies, and age at first full‐term pregnancy, were calculated conditioning by study, age, lifetime number of sexual partners and age at first sexual intercourse. Number of full‐term pregnancies was associated with a risk of invasive cervical carcinoma. After controlling for age at first full‐term pregnancy, the RR for invasive cervical carcinoma among parous women was 1.76 (95% CI: 1.53–2.02) for ≥≥7 full‐term pregnancies compared with 1–2. For CIN3/carcinoma in situ, no significant trend was found with increasing number of births after controlling for age at first full‐term pregnancy among parous women. Early age at first full‐term pregnancy was also associated with risk of both invasive cervical carcinoma and CIN3/carcinoma in situ. After controlling for number of full‐term pregnancies, the RR for first full‐term pregnancy at age <17 years compared with ≥≥25 years was 1.77 (95% CI: 1.42–2.23) for invasive cervical carcinoma, and 1.78 (95% CI: 1.26–2.51) for CIN3/carcinoma in situ. Results were similar in analyses restricted to high‐risk human papilloma virus (HPV)‐positive cases and controls. No relationship was found between cervical HPV positivity and number of full‐term pregnancies, or age at first full‐term pregnancy among controls. Differences in reproductive habits may have contributed to differences in cervical cancer incidence between developed and developing countries.

Tobacco attributable deaths in South Africa

Background: In mid 1998, a question “Was the deceased a smoker five years ago?” was introduced on the newly revised South African death notification form. Design: A total of 16 230 new death notification forms from 1998 have been coded, and comparison of the prevalence of smoking among those who died of different causes was used to estimate, by case–control comparisons, tobacco attributed mortality in South Africa. Cases comprised deaths from causes known (from other studies) to be causally associated with smoking, and controls comprised deaths from medical conditions expected to be unrelated to smoking. Those who died from external causes, and from diseases strongly related to alcohol consumption, were excluded. Subjects: Reports were available from 5340 deceased adults (age 25+), whose smoking status was given by a family member. Results: Significantly increased risks were found for deaths from tuberculosis (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.23 to 2.11), chronic obstructive pulmonary disease (COPD) (OR 2.5, 95% CI 1.9 to 3.4), lung cancer (OR 4.8, 95% CI 2.9 to 8.0), other upper aerodigestive cancer (OR 3.0, 95% CI 1.9 to 4.9) and ischaemic heart disease (OR 1.7, 95% CI 1.2 to 2.3). Conclusion: If smokers had the same death rate as non-smokers, 58% of lung cancer deaths, 37% of COPD deaths, 20% of tuberculosis deaths, and 23% of vascular deaths would have been avoided. About 8% of all adult deaths in South Africa (more than 20 000 deaths a year) were caused by smoking.

The spectrum of human immunodeficiency virus-associated cancers in a South African black population: results from a case-control study, 1995-2004

The effect of the evolving HIV epidemic on cancer has been sparsely documented in Africa. We report results on the risk of cancer associated with HIV‐1 infection using data from an ongoing study. A case–control analysis was used to estimate the relative risk (odds ratio, OR) of cancer types known to be AIDS defining: Kaposis sarcoma (n = 333), non‐Hodgkin lymphoma (NHL, n = 223) and cancers of the cervix (n = 1,586), and 11 cancer types possibly associated with HIV infection: Hodgkin lymphoma (n = 154), cancers of other anogenital organs (n = 157), squamous cell cancer of the skin (SCC, n = 70), oral cavity and pharynx (n = 319), liver (n = 83), stomach (n = 142), leukemia (n = 323), melanoma (n = 53), sarcomas other than Kaposis (n = 93), myeloma (n = 189) and lung cancer (n = 363). The comparison group comprised 3,717 subjects with all other cancer types and 682 subjects with vascular disease. ORs were adjusted for age, sex (except cervical cancer), year of diagnosis, education and number of sexual partners. Significantly increased risks associated with HIV‐1 infection were found for HIV/AIDS associated Kaposis sarcoma (OR = 47.1, 95% CI = 31.9–69.8), NHL (OR = 5.9, 95% CI = 4.3–8.1) and cancer of the cervix (OR = 1.6, 95% CI = 1.3–2.0); Hodgkins disease (OR = 1.6, 95% CI = 1.0–2.7), cancers of anogenital organs other than the cervix (OR = 2.2; 95% CI = 1.4–3.3) and SCC (OR = 2.6, 95% CI = 1.4–4.9) were also significantly increased. No significant associations were found between HIV and any of the other cancers examined. Risks for HIV‐related cancers are consistent with previous studies in Africa, and are lower when compared to those observed in developed countries.

Association between human immunodeficiency virus type 1 infection and cancer in the black population of Johannesburg and Soweto, South Africa

A case-control study of 913 black cancer patients (aged 15-50 years) was undertaken to measure the association between human immunodeficiency (HIV) infection and cancers believed to have an infective aetiology. Controls were patients with cancers believed not to be infective in origin. The prevalence of HIV in the controls of 7.3% (24 of 325) was similar to the background HIV seropositivity in this population. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, year of diagnosis, marital status and sex were calculated. There was a strong association between HIV infection and Kaposis sarcoma (KS), with 27 of 33 cases being HIV seropositive, OR = 61.8 (95% CI 19.7-194.2) and an elevated association with non-Hodgkins lymphoma (NHL), with 27 of 40 cases being HIV seropositive [OR = 4.8 (95% CI 1.5-14.8)]. The elevated odds ratio for KS associated with HIV infection accords with the observed increases in the incidence of KS in several sub-Saharan African countries where the prevalence of HIV is high. The odds ratio for NHL associated with HIV infection was lower than that reported in developed countries, and the reason for this is not clear. No other cancers, including cervical and liver cancers, showed significantly elevated odds ratios associated with HIV infection.