Trends in the burden of most common obesity-related cancers in 16 Southern Africa development community countries, 1990–2019. Findings from the global burden of disease study

1 BACKGROUND

It has been projected that by 2030, 70% of cancer deaths may occur in developing countries, and that these countries are expected to bear the bulk of the projected 24.1 million new cases annually.^{1, 2} High body mass index (BMI exceeding 25 kg/m²) has been described as the largest health threat facing mankind today.¹ Epidemiological studies have identified obesity as a risk factor for morbidity and mortality for many cancers such as esophagus, breast (in postmenopausal women), colon/rectal, uterus, gallbladder, kidney, liver, ovary, pancreas, and thyroid.^3-7 A meta-analysis of 57 prospective studies with 900,000 adults with over 6.5 million person-years found that mortality was lowest for individuals with BMI within the normal range (22.5–25.0 kg/m²), and particularly for women.⁸ Each increase in BMI of 5 kg/m² conferred a 29% increase in the hazard for all-cause mortality, hazard ratio [HR] 1.29 (95% confidence interval [CI]: 1.27–1.32), and a 10% increase in the hazard for cancer mortality, 1.10, (1.06–1.15).⁸

A causal relationship has been established between overweight (BMI ≥30 kgs/m²) and obesity (BMI: 25-<30 kg/m²) and cancer,⁹ but the role of increasing overweight and/or obesity on the trends of high-BMI-related cancers, particularly in developing countries, remains uncertain. Adults with obesity were reported to have a higher risk of cancer than those with a healthy weight in developed countries like the US.^{6, 7} Globally, an annual 0.6% increase was observed for the age-standardized mortality rate and the burden of cancer attributable to obesity was heavier in regions with higher Socio-Demographic Index (SDI) levels.¹⁰ The rate of incident cancers not associated with overweight and obesity decreased by 13%^{6, 7} while age-adjusted rates of incident cancers associated with obesity [oesophagus, breast (in postmenopausal women), colon/rectal cancer; uterus, gallbladder, kidney, liver, ovary, pancreas, and thyroid cancers] in the US increased by 7% for the period 2005 to 2014. Currently, there is no such comparable data for many developing countries, especially those of the SADC. Goal 3.4 of the United Nations General Assembly 2030 agenda for Sustainable Development Goals (SDGs) aims to reduce by one third premature mortality from non-communicable diseases (NCDs) with indicator 3.4.1 specifically seeking to reduce by one third the mortality rate attributed to conditions that are known to be causally associated with high BMI. Furthermore, epidemiologic analysis found “convincing or probable” evidence for a causal relationship between obesity^{11, 12} and 20 health outcomes including cancers of the oesophagus, colon/rectal, liver, gallbladder and biliary tract, pancreatic, breast, uterine, ovarian, thyroid and leukaemia.^13-30

Meta-analyses relative risks (RR) of the association ranged from 1.2 to 1.5 for overweight, and from 1.5 to 1.8 for obesity for cancers of the colon/rectal,^{13, 31} gastric cardia,³² liver,²⁴ gallbladder,³³ pancreas³⁴ and kidney cancers.²¹ The RR for oesophageal adenocarcinoma was as high as 4.8 for individuals with a BMI of 40 kg/m² or more.³⁵ However, 18 studies of the Asia Cohort Consortium found that the hazard ratios for oesophageal cancer and BMI formed a wide J-shaped association indicating mortality risk increase for underweight (BMI < 18.5 kg/m²: HR = 2.20, 95% CI = 1.80–2.70) and extreme obesity (BMI ≥ 35 kg/m²: 4.38, 2.25–8.52) relative to the referent BMI category of (23–25 kg/m²).³⁶ Other studies show substantial evidence of the positive association between increased BMI near the time of cancer diagnosis and reduced survival in patients with breast cancer^37-39; however, recipients of bariatric surgery for intentional weight loss reported reductions in cancer incidence and mortality indicating a negative association between cancers and low BMI.⁴⁰

Studies on cancer and BMI are extremely few in most developing countries.^41-43 The 16 countries that form the Southern Africa Development Community (SADC) shown in Figure 1 (Angola, Botswana, Comoros, Democratic Republic of Congo [DRC], Lesotho, Madagascar, Malawi, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Eswatini [formerly Swaziland], Tanzania, Zambia, and Zimbabwe) are no exception and they generally lack important information regarding the morbidity and mortality trends due to high-BMI-related cancers. As yet, there has not been any systematic understanding in SADC countries of the distribution of BMI related cancers and time trend analysis of the same. On the global scale, the International Agency for Research on Cancer's Global Cancer Observatory (GLOBOCAN) series estimated that there were 14.1 million new cancer cases and 8.2 million deaths worldwide in 2012 of which breast (1.67 million), and colorectal (1.36 million) were among the top three most commonly diagnosed, while liver (745,000 deaths), and stomach cancers (723,000 deaths) were among the top three most common causes of cancer death.⁴⁴ Projection estimates from GLOBOCAN 2020 Study indicated that of the 34 cancer types studied, 1.1 million new cases (95% UIs: 1.0 – 1.3 million) and 711,429 (611,604 – 827,547) deaths due to neoplasms occurred in Africa in 2020, and that by 2040, the burden of all neoplasms combined is expected to increase to 2.1 million new cases and 1.4 million deaths in Africa alone.⁴⁵ In 2019, for all countries of Africa, the Institute for Health Metrics and Evaluation (IHME) estimated a total of 71,708 breast cancer deaths, 48,639.97 deaths for colon/rectal cancer, 37,208 for liver cancer, 35,584.86 for oesophageal cancer 24,507 for pancreatic cancer, 17,624 for bladder cancer, 13,041 for ovarian cancer, 7366 for gallbladder and biliary tract cancer, 7201 for kidney cancer, 5901 for uterine cancer corresponding to age-standardized mortality rates (95% uncertainty interval (UI)) ranging from 10.89 (9.53–12.34) per 100,000 population for breast cancer to 1.02 (0.80–1.22) for uterine cancer.⁴⁶

Our previous report revealed that⁴⁷ age-standardized prevalence of overweight in adult females in SADC countries increased by 8.3% over a 30-year period from 31.4% (30.5–32.3) in 1990 to 39.7% (38.7–40.7) in 2019; and increased in males by 8.5% from 20.2% (19.5–20.8) to 28.7% (27.9–29.5).⁴⁸ Obesity in adult females increased by >1.5-fold and nearly doubled in adult males. Despite these increasing trends in obesity and overweight, compounded by the well-established causal relationship between obesity and several cancers, there is no known in-depth analysis of trends in morbidity and mortality associated with high-BMI-related cancers for SADC countries. As a result, a descriptive epidemiological analysis of mortality and prevalence associated with high-BMI-related cancers for SADC countries was conducted using data from the Global Burden of Diseases (GBD), Injuries and Risk Factor Study.⁴⁷ This information will aid key stakeholders to track progress and identify priorities for resource investment and/or develop corrective interventions to mitigate the interplay between obesity and related cancers.

2 METHODS

3 RESULTS

Our recent report found that obesity in adult females increased >1.5-fold from 12.0% (95% UI: 11.5–12.4) in 1990 to 18.5% (17.9–19.0) in 2017; in adult males, obesity nearly doubled from 4.5% (4.3–4.8) to 8.8% (8.5–9.2). Mean BMI increased from 22.4 kg/m² (21.6–23.1) to 23.1 kg/m² (22.3–24.0) in adult males, and from 23.8 kg/m² (22.9–24.7) to 24.8 kg/m² (23.8–25.8) in adult females.⁴⁵ Results presented in this paper should be considered in the above context.

4 DISCUSSION

This study was heavily guided and inspired by the serious lack of information on trends in morbidity and mortality associated with high-BMI-related cancers in SADC countries. It was also inspired by our report of 2021.⁴⁸ To our knowledge, this study represents the most comprehensive study so far that has reported the estimates of the burden of cancer due to obesity in SADC countries. Escalation of such diseases and other NCDs in the SADC countries requires information to highlight the impact and changes of high-BMI-related cancer burden on the populations for each of the countries to inform strategies and guide interventions to reduce the burden. The generally negative AROCs in males and females for oesophageal and leukaemia cancers provides evidence that mortality for these cancers is trending in the right direction but at a pace not rapid enough to meet the WHO UN SDG Target 3.4.

The increasing burden of high-BMI-related or lifestyle-related cancers in SADC between 1990 and 2019 could be explained by the epidemiological transition where populations move from contracting primarily communicable diseases to developing non-communicable diseases due to concomitant changes in lifestyle, dietary, and environmental exposures as well as increased access to health care, a combination which can similarly shift the distribution of non-communicable diseases or conditions characterized as “degenerative and man-made diseases”.^55-57 The other reason, in part, is the aging populations. The demographic transition theory suggests that as populations live longer and age substantially, there seems to be a correlated increase to lifetime risks for cancer. While the demographic transition proposes that neoplasms occur mostly in middle and old age, it is now known that they may not primarily or necessarily be caused by age-related biological processes of ‘degeneration’ but also by exogenous factors including poor diet, limited physical activity, sedentary lifestyle, and excessive alcohol consumption, all of which are mediated by rapid urbanization in developing countries.⁵⁸ The lifetime probability of developing cancer and cancer-related mortality in developed countries has already reached 56.9% and 27.6% in men, and 51.9% and 21.7% in women respectively.⁵⁹ African countries are at different stages of the demographic transitions, and even in-country transitions are at different levels that is, transitions are not monolithic, therefore interventions should be targeted to specific demographic patterns for each country and within country by region, such as rural/urban and other country-relevant subnational demarcations.

A major risk factor in developing cancer is obesity and/or high BMI. Generally, obesity is rising in developing countries; and the SADC is no exception. Among the many known and unknown reasons for this rise includes unhealthy diets and lack of preventive practices at both personal and policy levels⁶⁰ combined with rising disposable income.⁶¹ Observed obesity increase in Africa is largely caused by increasing urbanization,⁶² high changes in diet composition such as readily available and relatively cheaper fast foods confounded by dialogs comparing healthier foods as being harder to access and costly⁶³ reduced physical exercise, and sedentary life styles.⁴⁹ SADC countries should, as a matter of urgency start funding and developing public health and behavioral research interventions targeting these unhealthy behaviors with a focus on diet quality interrogations, caloric intake and physical activity, and the effect of rapid urbanization on childhood obesity and thereby suggest solutions as a way forward.⁶⁴

Apart from putting functional policies in place to effectively halt and reverse the occurrence of high-BMI-related cancers and mortality, African governments, especially in the SADC require investments in prevention and early detection and cancer care services. Currently, although the demand for cancer care has risen sharply, cancer care services are still limited and therefore, access to such is extremely difficult for many low-income cancer patients. For example, overweight and obesity were strongly associated with the later stages of breast cancer at diagnosis (stage III, IV) in Egypt,⁶⁵ however and perhaps due to lack of screening awareness among women with obesity, breast cancers were discovered quite late and when irreversible. Breast cancer survival for most cases is driven by early diagnosis. However, cancer survival rates are worse in the African population than in developed countries, with the 5-year survival rate of women with breast cancer in Europe being 82%, while it ranges between 12% and 46% in parts of Africa.⁶⁶ The call and need for SADC countries to invest in widespread cancer screening and early diagnosis and treatment together with preventive efforts at primary care facilities cannot be overstated.

It is our view that curtailing marketing of unhealthy food and promoting healthy ones, strengthening health promotion behaviors and awareness of risk factors may be valuable in contributing to the reduction of obesity and subsequently subduing the visible increases in high-BMI-related cancers. Health promotion messaging in SADC should target kidney, colon/rectal, pancreatic and breast cancers and encourage clinically tested methods of reducing BMI such as increasing personal levels of physical activity that produce results and adoption of dietary regimes that are equally effective. Several weight loss strategies have been successful, including dietary approaches such as low-calorie intake combining with behavioral therapy and behavioral dietary changes to support long-term weight loss maintenance.^{67, 68} Such strategies have been shown to reduce weight by approximately 3–5 kg after 1 year.⁶⁹ It is also true that certain observational studies have shown that consistent weight loss reduces the risk of cancer and therefore investment in such not-so-expensive therapies may suffice for the SADC. However, such studies maybe confounded by the fact that people who lose weight or avoid weight gain may differ in other ways from people who do not. For example, people who have lower weight gain during adulthood have lower risks of colon/rectal cancer, kidney cancer, and -for postmenopausal women—breast, endometrial, and ovarian cancers,^70-72 but counterfactually, individuals who have lower weight gain might also be more active or eat healthier.

The consumption of processed foods in Africa has increased in the last decades, with the downside impact of increased obesity⁷³ and cancer. SADC regions may require stringent and enforceable regulations to reduce uncontrolled access to ultra-processed foods.⁷³ The influence of ultra-processed foods (both imported and locally made) and poor food legislature, in addition to regulation enforcement may be notable factors driving the burden of obesity-related cancers. In developed countries, an increase in colorectal cancers have been attributed, in part, to high consumption of ultra-processed foods.⁷⁴ The consumption of processed foods has increased in SADC countries. In addition to locally processed foods, substantial increases in importation of poorly regulated processed drinks and foods from developed countries into the SADC region have dramatically increased. This is likely driven by a combination of the public need for cheaper food alternatives, and the need for increased business opportunities for regional and local importers, who create much needed employment and income opportunities.⁷⁵ Local food quality control has also been found lacking in SADC countries. Despite the well documented carcinogenic and health risk properties of mycotoxins, secondary fungal metabolites known to contaminate major staple foods in these regions, legislation controlling mycotoxin contamination of food is still limited in a number of SADC countries.⁷⁶ In addition, SADC populations, young and old, will benefit from awareness campaigns on food quality and conscious consumption through food label evaluation, specifically for those foods that may be associated with obesity and cancer.

Specific HIV treatment regiments have been associated with Obesity.⁷⁷ Considering that sub-Saharan Africa has the highest burden of people living with HIV and who are on anti-retroviral treatment, globally,⁷⁸ it is plausible that HIV treatment associated increases in BMI could also be driving increases in BMI-associated cancers in SADC. In addition, significantly improved survival of people living with HIV has resulted in notable increases in aging populations who may be at high risk of developing non-AIDS cancer,⁷⁹ and generally, increased risk of developing cancer due to advancing age.⁸⁰

Other more costly medical interventions that may allow the SADC to counter cancer progression could involve last resort surgical cancer care services not ideal for national rollout such as bariatric surgery for weight loss. Although such services are extremely limited and beyond the poor majority who may be at risk of such cancers, again, the demand in Africa is rising, although this may be an effective cancer prevention strategy needed to reduce cancer-related morbidity and mortality. Mortality studies have shown more robust protective hazards over 12.5 years for obesity related cancers due to such interventions as bariatric surgery, (HR = 0.62; CI: 0.49–0.78).⁸¹ On account of such overwhelming evidence, it is incumbent upon SADC countries to invest in surgical cancer care services as well. However, location-specific and culturally appropriate non-surgical interventions and strategies for weight loss are the most important since most SADC countries are generally poor and may not afford quick investment in surgical or indeed complex medical procedures.

This study reinforces conclusions of the IHME's Total Cancers report⁴⁷ and the GLOBOCAN 2020 analysis of 34 cancer types showing that high cancer mortality rates in Africa demand a holistic approach toward control and management such as increasing cancer awareness through health education, adoption of primary and secondary prevention methods through health promotion, mitigating risk factors, improving cancer infrastructure and robust screening, diagnosis, and timely treatment.^{45, 82} A large portion of the most rapidly rising cancers are avoidable by implementing public health. Such information is critical to help highlight the impact, changes and trends of high-BMI-related cancer burden on the populations for each of the countries to inform strategies and interventions to act to hopefully reduce the burden.

This study has some limitations. Firstly, period and cohort effects were not examined, which ideally would have allowed differentiation of the shift of cancer-related mortality risk by time periods and birth cohorts for each country so as to better appreciate effects of epidemiological and demographic transitions. To adequately capture time trends in mortality for each age-group adjusting for period effects, future analysis should use age-period-cohort models to analyze time trends in the burden of high-BMI-related cancers.⁸³ Secondly, specific population and country characteristics were not available to adjust for in the analyses. Future studies should tease out the intersection of obesity, different types of cancers (especially for breast cancer in females, and leukaemia, oesophageal, colon/rectal cancer in both sexes), and risk factors in the environment such as industrial pollution, air and water pollution as well as climate change. Other limitations of GBD estimates have been documented elsewhere.^{84, 85} Finally, information on country-specific policies were not available to address cancers, cancer-related care and mitigation.

5 CONCLUSION

Age-standardized death rates due to high-BMI-related cancers, especially kidney, colon/rectal, pancreatic and breast cancer in the SADC increased substantially in 2019. In particular, mortality due to breast cancer among males posted higher rates compared to cancers such as gallbladder/biliary tract, and thyroid cancers. Breast and other cancers were also significantly higher both at individual country level and across the SADC. However, it is important to note that while the situation requires maximum attention and intervention as well as investment in a number of programs including education, prevention and culturally sensitive aspects to curb cancers and related NCDs, SADC countries do actually have a “window” of opportunity to halt and reverse these negative health outcomes before they become endemic and out of control. Simple but comprehensive and broad implementation of known interventions at individual and community levels maybe starting points to fight off effects of both obesity and related cancers while looking forward to more intense policy shifts significant at individual country levels. Further and more focused research to identify tailored location-specific and more efficient strategies for weight loss and control, clinical trials of what works and what does not in different settings, as well as health promotion and health education are needed. Public funding for these strategies should be encouraged.

AUTHOR CONTRIBUTIONS

PNG conceptualized the study, had access to raw data, analyzed data, wrote the first draft of the manuscript, and interpreted the data, Clara M Gona, Suha Ballout, Chabila C Mapoma, Sowmya R Rao, contributed to the epidemiological, policy implications sections, and strengthened the intellectual content and recommendations of the study. Ali H. Mokdad supervised the development of the study, critiqued earlier drafts, and shaped the overall interpretation in relation to previous related studies. The authors read and approved the final manuscript. Please note: The publication is under the banner GBD 2019 SADC BMI. A full author list will be provided upon acceptance of the paper.

CONFLICT OF INTEREST STATEMENT

All authors report no conflicts.