Association between body mass index and major cancers with a focus on breast in South and Southeast Asia: A regional systematic review and meta-analysis

INTRODUCTION

Globally, the prevalence of obesity has nearly doubled since 1990.(1) According to the WHO, worldwide, 43% of adults aged 18 years and over were overweight, and 16% were obese in 2022.^[1] The prevalence of obesity is a growing concern across Asia, with projections indicating a significant increase in its incidence. According to the World Obesity Atlas of 2022, South and Southeast Asia are expected to see a doubling in the prevalence of obesity from 2010 to 2030.^[2] This trend highlights a serious public health challenge, as obesity is associated with various health risks such as diabetes, cardiovascular diseases, and certain cancers.

In 2020, the International Agency for Research on Cancer (IARC) published a report indicating a strong association between obesity and several types of cancer, including colon,^[3-5] breast, endometrial, kidney, and oesophageal cancer.^[6] A large population-based study involving 5.24 million adults in the UK and 166,955 new cases of 22 types of cancer demonstrated a strong association between BMI and several common cancers.^[7] Previous studies from different geographical regions have evaluated the association between overweight, obesity, and body mass index (BMI, kg/m²) as a measure of body weight and the risk of developing different types of cancer, including colorectal, endometrial, oesophageal, gallbladder, liver, and pancreatic cancers.^[8-11] In 2022, GLOBOCAN reported that lung (15.9%), breast cancer (10.0%), and colorectal cancers (9.8%) were the top three cancers in the Asia region.^[12] Several studies conducted in India, Bangladesh, and Indonesia have demonstrated a significant correlation between overweight and obesity and the incidence of breast cancer.^[13-18] An Asia Cohort Consortium (ACC) pooled study conducted in 2022 revealed a significant gender-specific association between BMI and thyroid cancer.^[19] A Japanese cohort study demonstrated a correlation between overweight and oesophageal cancer, but no clear association was found with BMI and non-cardia gastric cancer.^[20]

Previous systematic reviews and meta-analyses assessed the potential association between overweight and obesity and total as well as site-specific cancer.^[21-28] Some studies included obesity as a factor in determining survival outcomes of cancer patients.^[27,28] However, the definition of obesity is often heterogeneous, and results for Asian populations are lacking. In addition, a systematic review and meta-analysis of 221 datasets (141 articles) comprising 282,137 incident cases from multiple regions reported that in the Asia-Pacific region, increased BMI was positively associated with both premenopausal and postmenopausal breast cancer.^[29] A weaker positive association was observed for men and women in the correlations between BMI and malignant melanoma, multiple myeloma, rectal cancer, leukaemia, non-Hodgkin lymphoma, thyroid, pancreas, and colon cancer.^[29] In 2017, another meta-analysis in Southeast Asia reported that BMI was positively correlated with survival outcomes in patients with breast cancer.^[30] Cancer incidence patterns in South and Southeast Asia differ from those observed in high-income regions due to variations in body composition, environmental exposure, and healthcare system capacity. Several epidemiological studies have examined the link between body mass index (BMI) and cancer risk in Asian populations. However, the results are inconsistent and often limited to one type of cancer or one country. Furthermore, inconsistent BMI classification and study design make it difficult to interpret and compare results from different studies. Despite the region's distinguishing epidemiological profile, few systematic reviews have focused specifically on South and Southeast Asia.

Despite these findings, a significant research gap remains: few studies have comprehensively examined how BMI influences cancer risk across South and Southeast Asia. However, the specific relationship between BMI and site-specific cancer incidence in this region remains inadequately investigated. To address this gap, we conducted a comprehensive literature review and meta-analysis to evaluate the association between BMI (overweight, obesity, and underweight) and site-specific cancer incidence in South and Southeast Asia.

MATERIALS AND METHODS

Data sources and search strategy

We conducted a computerised systematic search in four databases, including PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL), and Web of Science from 2000 to April 2023. The essential concept of the data search for the systematic review and meta-analysis was as follows: (Cancer OR oncology OR malignancy OR neoplasms) and (Overweight OR obese OR obesity OR body weight OR body mass index) and (South Asia) and (Southeast Asia). The full search strategy and results from each database search are described in Supplementary Tables 1-8. We limited our search to adult cancer and excluded case reports, systematic reviews, meta-analyses, animal studies, childhood cancer, skin cancer, melanoma, laboratory studies, and pediatric cancer. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guideline [Figure 1]. The study protocol was registered with the International Prospective Register of Systematic Reviews PROSPERO (registration No: CRD42023427644).

SUPPLEMENTARY FILE

Download

Close

Figure 1:

PRISMA flowchart for selection of studies. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analysis

Export to PPT

RESULTS

Figure 1 presents a flow diagram of the literature search conducted in accordance with the PRISMA guidelines. A total of 1,361 studies were identified through an electronic search on PubMed, Embase, CINAHL, and Web of Science. Of these, 293 duplicates were excluded, leaving 957 studies for title and abstract screening. Furthermore, 122 additional irrelevant articles were excluded based on the established inclusion criteria. Subsequently, 81 articles were excluded for the following reasons: a lack of exposure data (n=11), an incorrect outcome (n=24), an inappropriate population (n=11), and other reasons (n=35). A further five articles were identified through citation searching. Finally, 46 studies were selected for our systematic review and meta-analysis. Out of 46 studies, 26 studies were selected for meta-analysis, and 20 studies were included only in the narrative summary.

Tables 1 and 2 shows the background characteristics of all 46 included studies. The selected studies were published between 2000 to 2023.^{[3-5, 13-18, 32-68]} We included six cohort studies and 34 case-control studies in the analysis. Additionally, six cross-sectional studies, excluded from the meta-analysis, were reported only in the narrative summary. Most studies evaluated overweight (32 studies [70%]), obesity (20 studies [43%]), and BMI (six studies [14%]). We identified 30 studies for breast cancer, four studies for colorectal cancer, while studies for the remaining cancer sites (cervical cancer, prostate cancer, oral cancer, esophageal cancer, gallbladder cancer, lung cancer, colon cancer, endometrial cancer) were too scarce for the meta-analysis. The selected studies covered 11 different countries. The highest number of studies was from India (16 studies, 35%) followed by Pakistan (six studies, 13%). According to the Newcastle-Ottawa scale, 95% of the included studies were of high or moderate quality (score of at least 6). [Supplementary Tables 7 and 8]

A total of 19 studies were included in the meta-analysis investigating the association between overweight and breast cancer [Figure 2]. The pooled OR for the association between overweight and breast cancer was 1.29 (95% CI: 1.02-1.64), with considerable eterogeneity (I² = 87.31%).

Close

Figure 2:

Association of overweight and breast cancer Note: Overweight include all definition WHO (25-29.9) and Asia (23-24.9). OR: Odds ratio, CI: Confidence interval

Export to PPT

Figure 3 depicts the association between obesity and breast cancer. The pooled OR for obesity and breast cancer was 1.82 (95% CI: 1.21-2.75), with considerable heterogeneity (I²=87.68%). To address potential bias and verify our results, we performed sensitivity analyses excluding highly influential studies with small effect sizes. By omitting individual studies and recalculating the pooled ORs for the remaining studies, we found no changes in the direction of the effect when any single study was excluded. [see Supplemental Figures 1 and 2]. The funnel plots and Egger test were indicated that there was no evidence of publication bias for overweight and breast cancer (p-value for Egger test=0.13), but the publication bias was present among the studies investigating the association between obesity and breast cancer (p-value for Egger test=0.02) [Figures 4]. The association of underweight (BMI<18.5 kg/m²) and breast cancer is presented in [Supplemental Figures 3-5]. We found no significant association between underweight and breast cancer. The pooled OR was 0.65 (95% CI: 0.18-2.25) with high heterogeneity (I² =83.66%). Results for other cancer sites were too sparse to justify a meta-analysis.

Close

Figure 3:

Association of obesity and breast cancer Note: Obesity include all definition WHO (>=30) and Asia (>=25). OR: Odds ratio, CI: Confidence interval

Export to PPT

Close

Figure 4:

Funnel plot for breast cancer (A) Overweight and (B) Obesity. CI: Confidence interval

Export to PPT

A subgroup analysis was conducted to investigate the relationship between overweight and obesity and breast cancer, with respect to region, country, study design, sample size, and study quality [Table 3]. A subgroup analysis by geographic region revealed a higher risk of breast cancer in South Asia for individuals with obesity (OR: 2.01; 95% CI: 1.36-2.99). The p-value for the Q-statistic was greater than 0.05 for both overweight and obesity, indicating that the pooled OR was not significantly different between regions. Due to the limited number of studies conducted in Bangladesh, the pooled OR for breast cancer in overweight and obese individuals was higher than in other countries (OR: 4.66; 95% CI: 2.58-8.40 for overweight and OR: 3.91; 95% CI:1.0-15.3 for obese) compared to other countries. The p-value for the Q-statistic was less than 0.05, which indicates that the pooled OR significantly differed between countries. Furthermore, the data were stratified according to the definitions of BMI proposed by the WHO and the Asian region. The pooled OR for the Asian definition was 1.14, while that for the WHO definition was 1.43. The p-value for Q statistics was 0.56 see [Supplementary Figures 4 and 5], indicating that there was no statistically significant difference between the two definitions. In the case of obesity, the p-value for Q-statistics was 0.98, indicating that there was no statistically significant difference between the two definitions. The pooled OR for obesity in cohort studies demonstrated a significantly higher OR for breast cancer compared to that observed in case-control studies.

Table 4 presents a narrative summary of the relationship between overweight/obesity and cancer risk. In the narrative summary, we observed an association between BMI and different sites of cancer among 28 studies. Out of 12 studies, 4 studies reported a positive association with BMI and breast cancer, and 3 of 5 studies for colorectal cancer. The result of two studies indicated an insignificant association between overweight and cancers of the colon and cervix. A positive correlation was observed between obesity and endometrial cancer. The findings of studies conducted on esophageal and gastric cancers have indicated an evident non-association with BMI.

DISCUSSION

This is one of the first studies to systematically explore the association between overweight and obesity and multiple cancer sites in South and Southeast Asian countries. The present systematic review and meta-analysis include 45 studies on BMI and different sites of cancer incidence, and results showed that being overweight and obesity are significantly associated with an increase of breast cancer in South and Southeast Asia. Based on the results, overweight women had a 1.29 times risk of developing breast cancer compared to normal BMI women, and obese women had a 1.82 times risk of developing breast cancer. The result indicated that obese women had a higher chance of developing breast cancer than overweight women. Additionally, our findings indicate that there is no significant difference between the two regions, sample sizes, or study quality regarding overweight and obesity. Most importantly, we observed no difference by WHO and the Asian definition of BMI categories. However, we did identify notable differences between countries, notably Bangladesh showing the highest OR for both overweight and obesity, possibly due to difference in lifestyle, sample characteristics, or genetic factors.^[34] Furthermore, our narrative summary identified positive associations between overweight and obesity and other forms of cancer, for example, colorectal, endometrial, and cervical cancer. No relationship was found between BMI and esophageal and gastric cancer.

The results of this study are in line with previous studies, which showed an association of overweight and obesity with breast cancer during the menopausal period in Asian countries.^[69,70] Other studies from Europe and North America found an inverse association between high BMI and the risk of breast cancer in premenopausal women.^[71-73] Furthermore, an additional study from the Philippines found no correlation between BMI and breast cancer.^[51] Additionally, when stratified by menopausal status, no statistically significant association was observed.^[51] However, some research indicates that women who are overweight or obese in the premenopausal period may have a reduced risk of developing breast cancer.^{[73, 74]} Interestingly, two studies from India and Malaysia reported contradictory findings with high BMI being associated with a lower risk of breast cancer.^{[36, 46]} It seems probable that the current BMI estimates were used, but the weight subsequently decreased. Studies in India, Thailand, and Vietnam have identified an association between BMI and an increased risk of breast cancer.^[13,54,55] Our systematic review and meta-analysis confirmed that breast cancer in South and Southeast Asia is significantly correlated being overweight and obesity. Stratified analyses by sub-regions suggested no difference between them. The findings emphasize the need for targeted public health interventions to address obesity and promote healthy lifestyles in these regions.

The results of our study indicate a correlation between BMI and not only breast cancer but also other cancer sites. As with our present findings, a meta-analysis of studies conducted in high- and middle-income countries demonstrated that individuals with a higher BMI are at an elevated risk of developing colorectal cancer in comparison to those with a normal weight.^[75] Additionally, a cohort study and a meta-analysis in an Asian country also identified a positive correlation between BMI and the risk of developing colorectal cancer incidence and mortality.^[8,76] Another meta-analysis provided strong support for the association between excess body weight, overweight, and obesity and endometrial cancer risk.^[77] Similar to our narrative findings, a meta-analysis result indicated that obesity was associated with the risk of gastric cancer.^[78] A 2020 meta-analysis hypothesized that overweight might be a protective factor in gastric cancer risk in Asian adults.^[79] The present study underscores a substantial evidence gap regarding the association between BMI and site-specific cancer risk in South and Southeast Asia. The majority of available studies focus on breast cancer, with limited data on other common cancers such as colorectal, prostate, and lung cancer. Most studies used a case–control design, with only a few being long-term cohort studies. Because of this, we cannot be sure about cause and effect, so the link between BMI and cancer risk should be interpreted with caution. It is imperative that future research prioritizes prospective studies with standardized BMI measurement, stratification by menopausal status, and evaluation of other risk modifiers such as diet, physical activity, and metabolic health.

To our best knowledge, this is the first comprehensive systematic review and meta-analysis on BMI to include multiple cancer sites from South and Southeast Asia. The main strength is that we included all types of observational studies, including case-control, cohort and cross-sectional studies. The large sample size provides a more precise result and a narrower confidence interval than obtained from previous meta-analyses. The study has a few limitations. While the search strategy included a comprehensive 20 countries from South and Southeast Asia, we only identified articles from 11 countries (Afghanistan, Bangladesh, India, Pakistan, Philippine, Singapore, Sri Lanka, Thailand, and Vietnam). Due to a lack of comparable data on multiple cancer sites, we only conducted the meta-analysis for breast cancer. We were not able to conduct a stratified analysis by pre- and post-menopausal women. Additionally, cancer incidence data are not available for all Asian countries due to limited high-quality cancer registries in the region.

CONCLUSION

In conclusion, being overweight or obese raises the risk of breast cancer and other cancers in South and Southeast Asia. This review provides a comprehensive synthesis of the available evidence, but the predominance of case-control studies limits causal inference. To improve the quality of the evidence base and clarify the relationship between BMI and cancer risk, future large-scale prospective cohort studies are needed in South and Southeast Asia. The implications of our results are profound, emphasizing the need for targeted public health interventions to address obesity and its related health risks. Strategies should include promoting healthy dietary practices, increasing physical activity, and implementing policies that foster environments conducive to healthy living. Furthermore, this review underscores the importance of culturally tailored cancer prevention programs that consider regional dietary habits, socioeconomic factors, and healthcare access. Further research is needed to explore the underlying mechanisms and develop region-specific guidelines.