Assessing the Global Impact of Ambient Air Pollution on Cancer Incidence and Mortality: A Comprehensive Meta-Analysis

Abstract

PURPOSE

This study aims to examine the association between exposure to major ambient air pollutants and the incidence and mortality of lung cancer and some nonlung cancers.

METHODS

This meta-analysis used PubMed and EMBASE databases to access published studies that met the eligibility criteria. Primary analysis investigated the association between exposure to air pollutants and cancer incidence and mortality. Study quality was assessed using the Newcastle Ottawa Scale. Meta-analysis was conducted using R software.

RESULTS

The meta-analysis included 61 studies, of which 53 were cohort studies and eight were case-control studies. Particulate matter 2.5 mm or less in diameter (PM_2.5) was the exposure pollutant in half (55.5%), and lung cancer was the most frequently studied cancer in 59% of the studies. A pooled analysis of exposure reported in cohort and case-control studies and cancer incidence demonstrated a significant relationship (relative risk [RR], 1.04 [95% CI, 1.02 to 1.05]; I², 88.93%; P < .05). A significant association was observed between exposure to pollutants such as PM_2.5 (RR, 1.08 [95% CI, 1.04 to 1.12]; I², 68.52%) and nitrogen dioxide (NO₂) (RR, 1.03 [95% CI, 1.01 to 1.05]; I², 73.52%) and lung cancer incidence. The relationship between exposure to the air pollutants and cancer mortality demonstrated a significant relationship (RR, 1.08 [95% CI, 1.07 to 1.10]; I², 94.77%; P < .001). Among the four pollutants, PM_2.5 (RR, 1.15 [95% CI, 1.08 to 1.22]; I², 95.33%) and NO₂ (RR, 1.05 [95% CI, 1.02 to 1.08]; I², 89.98%) were associated with lung cancer mortality.

CONCLUSION

The study confirms the association between air pollution exposure and lung cancer incidence and mortality. The meta-analysis results could contribute to community cancer prevention and diagnosis and help inform stakeholders and policymakers in decision making.

INTRODUCTION

Global cancer burden has been on a rapid rise. In the year 2020, there were an estimated 19.3 million newly reported cases of cancer, resulting in the tragic loss of 10 million lives.¹ Cancer ranks as the foremost or second most prominent cause of premature death in 134 of 183 countries.² In terms of disability-adjusted life years (DALYs), which is a measure of the years of healthy life lost because of illness, disability, or premature death, cancer is the second leading cause, accounting for approximately 9.93% of total DALYs worldwide in 2019, after cardiovascular diseases.³ Lifestyle risk factors which are potentially modifiable, including behavioral, environmental, and occupational risk factors, contributed to 44.4% of all cancer deaths and 42% of all DALYs in 2019.⁴ Cancer burden varies across the countries, with the highest incidence in the WHO Europe region (age-standardized rate [ASR], 234.6 per 100,000 population) and lowest in the WHO Southeast Asia region (ASR, 98.1 per 100,000 population).⁵ The differences could be attributed to various factors such as lifestyle, genetics, environmental factors, and access to cancer screening and treatment.

Ambient air pollution has been a significant environmental factor affecting human health. WHO defines ambient air pollution as potentially harmful pollutants emitted by industries, households, cars, and trucks. In 2019, 99% of the global population resided in areas where air quality failed to meet the WHO standards.⁶ In India, air pollution has been associated with a high mortality burden, morbidity, and economic loss.⁷ Indoor and outdoor air pollution is the third and ninth risk factor for worldwide mortality and morbidity and is linked to several chronic noncommunicable conditions such as cancers, including lung, cervical, and brain cancers; cardiovascular diseases; chronic obstructive pulmonary diseases; and asthma.^8-15 Air pollution in India accounts for 17.8% (1.67 million) of all deaths and financial losses, amounting to $28.8 billion in US dollars.⁷

The composition of air pollution and levels of exposure can exhibit substantial variation, contingent on factors such as the season, the weather conditions, and the variety of pollution sources. Among all the pollutants, fine particulate matter (<2.5 μm) significantly affects human health. Lozano et al¹⁶ found that airborne particulate matter 2.5 μm or less in diameter (PM_2.5) in the air contributes to an estimated 2 million premature deaths each year, positioning it as the 13th leading cause of mortality worldwide. Earlier studies have reported a positive association between ambient air pollution and cancers of the pancreas, urinary bladder, breast, prostate, and liver.^17-22 The International Agency for Research on Cancer classifies outdoor air pollution and airborne particulate matter of 2.5 µm or less (PM_2.5) as a group 1 carcinogen contributing to human lung cancer. In addition, there exists weak evidence for urinary bladder, breast, childhood leukemia, liver, pancreatic, kidney, cervical, and brain cancer sites. However, there is no evidence for head and neck, bone cancer, soft tissue tumor, corpus uteri, ovary, prostate, and thyroid cancers.²³

While past research has extensively investigated the connection between air pollution and lung cancer globally,^24-28 there is still limited evidence on the association between air pollution and the incidence of nonlung cancer. This study aims to fill that gap by examining the association between exposure to major ambient air pollutants and the incidence and mortality of lung cancer and some nonlung cancers.

METHODS

This study followed the systematic review and meta-analysis techniques defined by the Cochrane Collaboration. It adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Protocols guidelines.²⁹

Eligibility Criteria

Inclusion Criteria

The following were considered for study inclusion: (1) original article; (2) human studies; (3) major air pollutants: PM_2.5, particulate matter 10 mm or less in diameter (PM₁₀), nitrogen dioxide (NO₂), and ozone (O₃); (4) studies reporting the cancer incidence and mortality in people exposed to air pollution in the following sites: breast, liver, lung, pancreas, and urinary bladder cancer; (5) cohort and case-control studies; (6) reported outcome measures in terms of odds ratio (OR), relative risk (RR), and hazard ratio (HR) along with 95% CI; (7) full-text article in English; and (eight) studies conducted over the past 20 years, that is, from January 1, 2001 to December 30, 2021.

Exclusion Criteria

The following were considered for exclusion: (1) case reports, case studies, reviews, and correspondences; (2) studies focused on exposures to pollutants because of occupation or accidents; (3) non-English literature; and (4) articles not reporting outcome, exposure, and outcome measure of interest.

Data Sources and Search Strategy

PubMed and EMBASE databases were used to access published studies that met the eligibility criteria. The search strategies were based on a combination of keywords concerning air pollution (outdoor, ambient, traffic), air pollutants (particulate matter, PM_2.5, PM₁₀, NO₂, O₃), cancer (malignancy, carcinoma, neoplasm, breast, liver, lung, pancreatic, and urinary bladder cancers), and outcome indicators (incidence, mortality). In addition, we looked through the bibliographies of relevant publications for more information. The keyword combinations used for the literature search in Embase and PubMed databases are listed in the Data Supplement (Table S1). The data extracted included the first author's name, title, year of publication, study setting, study design, study duration in case of cohort studies, sex, type of air pollutant, mean concentrations of air pollutants, assessment of air pollution exposure, sample size, anatomic cancer site, adjusted confounding variables, and measure of effect size (RR, OR, or HR) with 95% CI. Two independent investigators performed the study selection, and a third person resolved any disagreements.

Assessment of Methodologic Quality

The quality of selected studies was evaluated using the Newcastle Ottawa Scale (NOS).³⁰ Each study was assessed on a NOS score from zero to nine. The studies were classified as low quality if the NOS score is ≤six and high quality if the score is >six.

Risk of Bias Assessment

The assessment of potential risk of bias was conducted using the Risk of Bias in Nonrandomized Studies-of Exposure (ROBINS-E) tool. This tool is primarily designed for systematic reviews and aims to gauge the strength of evidence regarding exposure's presence and potential effect on a given outcome.³¹ An integral aspect of the ROBINS-E methodology involves specifying, for each study, the causal impact estimated by the outcome under consideration.

Statistical Analysis

The primary analysis investigated the association between exposure to air pollutants and cancer incidence and mortality. To calculate the RR, we used a standardized incremental approach for each pollutant, using the given formula:³²

$${\text{RR standardized = e}}^{\left(\frac{\text{ln}\left({\text{RR}}_{\text{Origin}}\right)}{{\text{Increment}}_{\text{Origin}}}\times {\text{Increment}}_{\text{Standardized}}\right)}$$

Meta-analysis was conducted using R software (V 4.2.2, R: Core Team, Vienna, Austria). A heterogeneity assessment was performed to evaluate the consistency of the exposure-outcome association across the studies or populations. The Higgins I² statistic evaluated heterogeneity among the included studies.³³ The study was defined as having substantial heterogeneity with a χ² test P value of ≤.05 and an I² test value of >50%. A random-effects model was used for analysis on the basis of the DerSimonian and Laird method.³⁴ Pooled effect size (RR) and 95% CIs were calculated using this model and presented using a forest plot. A funnel plot was constructed to help identify publication bias.³⁵ Statistical tests, namely, the Begg and Egger tests, were used to check the asymmetry in the studies, and the P < .05 representative statistic was considered significant. The Institutional Ethics Committee of Indian Council of Medical Research -National Centre for Disease Informatics and Research (ICMR-NCDIR) approved the study (NCDIR/IEC/3051/2021).

RESULTS

A comprehensive search across Embase and PubMed and a review of the reference lists of selected papers produced 6,409 articles. After excluding 3,983 duplicates, 2,426 articles were chosen to screen titles. This resulted in 1,347 articles for full-text reading (Fig 1). The meta-analysis included 61 studies,^{19,20,36‐94} of which 53 were cohort studies and eight were case-control studies. The characteristics of included studies that analyzed the association between air pollution and cancer incidence or mortality are shown in the Data Supplement (Tables S2 and S3). Among studies on the association between air pollution and cancer incidence, most (78%) comprised prospective cohort studies. PM_2.5 was the exposure pollutant in half (55.5%), and lung cancer was the most frequently studied cancer in 59% of the studies. The number of study participants ranged from 799 to 78,822,970. Regarding studies on the association between air pollution and cancer mortality, 64% assessed PM_2.5 as an exposure pollutant, and lung cancer was the most common cancer to be examined (79%). The sample size ranged from 2021 to 7,218,363.

FIG 1.

Flow diagram showing the selection of eligible studies.

Risk of Bias and Study Quality

Most studies (44.4%) on cancer risk and 38.2% on cancer mortality were estimated to have a low risk of bias (Data Supplement, Tables S4 and S5). Most studies predicted that direction of bias was toward the harm of exposure. Most of the studies had an NOS score of seven and above among cancer incidence and mortality studies (Data Supplement, Tables S6 and S7).

Air Pollution and Cancer Incidence

A pooled analysis of exposure reported in cohort and case-control studies ^19,20,36-60 and cancer incidence demonstrated a significant relationship (RR, 1.04 [95% CI, 1.02 to 1.05]; I², 88.93%; P < .05; Fig 2). Similar findings were reported on subgroup analysis (Table 1) on the basis of study design: cohort studies (RR, 1.03 [95% CI, 1.02 to 1.05]; I², 90.92%; P < .05) and case-control studies (RR, 1.05 [95% CI, 1.02 to 1.09]; I², 0.00%; P < .05) and among males (RR, 1.07 [95% CI, 1.04 to 1.10]; I², 90.92%; P < .05) and females (RR, 1.04 [95% CI, 1.01 to 1.06]; I², 86.95%; P < .05).

FIG 2.

Forest plot for the association between all air pollutants (PM_2.5, PM₁₀, NO₂, and O₃) and incidence of all included cancers. BG, both genders; M, men; W, women.

TABLE 1.

Subgroup Analysis of Exposure to All Air Pollutants (PM_2.5, PM₁₀, NO₂, and O₃) and Cancer Incidence

Subgroup	No. of Studies	Effect Size (95% CI)	Q	P > Q	Tau2	I2, %	Egger's Test
Overall	27	1.036 (1.021 to 1.051)	541.76	<.001	0.002	88.93	0.0093
Sex
Male	5	1.066 (1.036 to 1.097)	16.38	.003	0.0001	75.58	0.4493
Female	28	1.037 (1.013 to 1.062)	206.94	<.001	0.0022	86.95	0.4224
Study designa
Cohort	49	1.034(1.017 to 1.050)	528.36	<.001	0.0016	90.02	0.1165
Case control	12	1.054 (1.021 to 1.086)	10.83	.4576	0	0	0.0334
Region
Western Pacific	4	1.082 (1.072 to 1.091)	3.62	.3058	0	17.07	0.3542
European region	28	1.055 (1.020 to 1.090)	75.05	<.001	0.0042	64.02	0.6283
Region of Americas	29	1.013 (1.000 to 1.025)	120.84	<.001	0.0004	76.83	0.0028
Site of cancerb
Lung	30	1.049 (1.026 to 1.072)	436.5	<.001	0.0019	93.36	0.0135
Breast	19	1.016 (0.999 to 1.032)	41.64	.0012	0.0004	56.78	0.048
Urinary bladder	8	1.021 (0.980 to 1.061)	8.75	.2708	0.0007	20.04	0.5289
Pollutant
PM2.5	22	1.054 (1.024 to 1.084)	54.01	.0001	0.0014	61.12	0.3316
PM10	10	1.041 (0.991 to 1.091)	20.66	.0143	0.0025	56.43	0.0199
O3	5	1.001 (0.923 to 1.078)	321.51	<.001	0.006	98.76	0.8921
NO2	22	1.030 (1.017 to 1.043)	56.95	<.001	0.0002	63.12	0.0078
Quality score
More than six	57	1.034 (1.018 to 1.049)	528.96	<.001	0.002	89.41	0.0108
Six and less	4	1.077 (0.989 to 1.165)	7.60	.055	0.004	60.52	0.8932
Risk of bias
High risk	7	0.996 (0.962 to 1.03)	7.70	.261	0.000	22.12	0.1539
Low risk/some concerns	54	1.039 (1.024 to 1.055)	508.77	<.001	0.002	89.58	0.0197

^aSimilar result was found when analyzed using the fixed-effect model

^bNo eligible study was identified for pancreas, and only one study was found for liver cancer

The results of subgroup analysis according to the geographic region demonstrated a significantly higher association between air pollution and cancer incidence in the Western Pacific region with low heterogeneity (RR, 1.08 [95% CI, 1.07 to 1.09]; I², 17.07%; P < .05) compared with the European region (RR, 1.06 [95% CI, 1.02 to 1.09]; I², 64.02%) and the Americas (RR, 1.01 [95% CI, 1.00 to 1.03]; I², 64.02%; P < .05).

A significant association was observed between exposure to pollutants such as PM_2.5 (RR, 1.08 [95% CI, 1.04 to 1.12]; I², 68.52%) and NO₂ (RR, 1.03 [95% CI, 1.01 to 1.05]; I², 73.52%) with lung cancer incidence (shown in Data Supplement, Figure S3). However, the association between exposure to air pollutants and incidence of breast, liver, pancreatic, and urinary bladder cancers was not significant, as shown in Table 1 (Data Supplement, Figures S4 and S5).

Air Pollution and Cancer Mortality

The relationship between exposure to the air pollutants and cancer mortality demonstrated a significant relationship (RR, 1.08 [95% CI, 1.07 to 1.10]; I², 94.77%; P < .001), as shown in Table 2. Similar findings were reported on subgroup analysis among males (RR, 1.07 [95% CI, 1.03 to 1.11]; I², 78.37%; P < .0001) and females (RR, 1.08 [95% CI, 1.04 to 1.12]; I², 48.71%; P < .05; Fig 3).^61-72

TABLE 2.

Subgroup Analysis of Exposure to All Air Pollutants and Cancer Mortality

Subgroup	No. of Studies	Effect Size (95% CI)	Q	P > Q	Tau2	I2, %	Egger’s Test
Overall	74	1.086 (1.070 to 1.102)	1,395.09	<.0001	0.0019	94.77	0.000
Sex
Male	10	1.071 (1.028 to 1.114)	41.61	<.0001	0.0029	78.37	0.3583
Female	20	1.082 (1.044 to 1.120)	37.04	.0078	0.0024	48.71	0.0042
Region
Western Pacific	13	1.153 (1.094 to 1.211)	132.59	<.0001	0.0071	90.95	0.0032
European region	20	1.113 (1.061 to 1.165)	214.66	<.0001	0.0064	91.15	<0.0001
Region of Americas	41	1.067 (1.045 to 1.088)	988.77	<.0001	0.0017	95.95	0.0642
Site of cancer
Lung	47	1.097 (1.078 to 1.115)	1,302.95	<.0001	0.0018	96.47	<0.0001
Nonlung cancer	27	1.069 (1.023 to 1.116)	92.14	<.0001	0.0069	71.78	0.0005
Quality score
More than six	67	1.082 (1.064 to 1.099)	1,352.07	<.0001	0.002	95.11	<0.0001
Less than six	7	1.137 (1.072 to 1.202)	24.56	.0004	0.0029	75.57	0.0925
Risk of bias
Yes	13	1.114 (1.083 to 1.144)	916.74	<.0001	0.0015	98.69	0.0288
No	61	1.091 (1.06 to 1.119)	453.96	<.0001	0.0068	86.78	<0.0001

FIG 3.

Forest plot for the association between all air pollutants (PM_2.5, PM₁₀, NO₂, and O₃) and mortality due to included cancers in females and males.

The results of subgroup analysis (Table 2) according to the geographic region demonstrated a significantly higher association between air pollution and cancer mortality in the Western Pacific region (RR, 1.15 [95% CI, 1.09 to 1.21]; I², 90.95%; P < .0001) compared with the European region (RR, 1.11 [95% CI, 1.06 to 1.16]; I², 64.02%) and the Americas (RR, 1.07 [95% CI, 1.04 to 1.09]; I², 95.95%; P < .05).

A significant association was noted between all four air pollutants and lung cancer mortality (RR, 1.10 [95% CI, 1.08 to 1.11]; I², 96.82%; Fig 4).^{35,61,62,65,66,67,71,72,73‐100} Among the four pollutants, PM_2.5 (RR, 1.15 [95% CI, 1.08 to 1.22]; I², 95.33%) and NO₂ (RR, 1.05 [95% CI, 1.02 to 1.08]; I², 89.80%) were associated with lung cancer mortality. A significant relationship was observed between the air pollutants and breast cancer mortality (RR, 1.14 [95% CI, 1.05 to 1.23]; I², 30.64%; P > .05), as shown in Figure 5. In addition, a significant association was found between pollutants such as PM_2.5 (RR, 1.20 [95% CI, 1.05 to 1.35]; I², 45.00%) and PM₁₀ (RR, 1.11 [95% CI, 1.01 to 1.20]; I², 0.00%) and breast cancer mortality. A significant association was also noted between PM_2.5 exposure (RR, 1.14 [95% CI, 1.04 to 1.24]; I², 00.00%) and liver cancer mortality as presented in Figure 6.

FIG 4.

Forest plot for the association between air pollutants (PM_2.5, PM₁₀, NO₂, and O₃) and lung cancer mortality.

FIG 5.

Forest plot for the association between air pollutants (PM_2.5, PM₁₀, NO₂, and O₃) and breast cancer mortality.

FIG 6.

Forest plot for the association between air pollutants (PM_2.5, PM₁₀, NO₂, and O₃) and liver cancer mortality.

Publication Bias

The assessment of publication bias for the studies included in the meta-analysis is graphically presented in the Data Supplement (Figs S1 and S2). P values exceeding .05 in Egger's test suggest the absence of significant evidence for publication bias.

DISCUSSION

This meta-analytical study incorporated data from 53 cohort and eight case-control studies that met the specific study selection criteria. The study demonstrated a significant relationship between all exposure to PM_2.5, PM₁₀, NO₂, and O₃ and cancer incidence and mortality in five sites: breast, liver, lung, pancreas, and urinary bladder. The strength of association for cancer incidence was higher in males than females, which could be attributed to higher rates of smoked tobacco use in males.⁹⁵ Aggregate findings from another meta-analysis by Huang et al indicated that former smokers might face a heightened lung cancer risk linked to PM_2.5 compared with current smokers and individuals who have never smoked across mortality, incidence, and complete meta-estimates.⁹⁶ Concerning cancer mortality, the strength of association was higher in females than males. In low- and middle-income countries, women experience higher mortality rates from cancer compared with their counterparts in high-income countries although the overall incidence of cancer is lower among them. This disparity can be primarily attributed to limited access to early detection and treatment options.⁹⁷ One of the most frequently proposed mechanisms to explain the connection between exposure to air pollution and cancer mortality is the acceleration of cancer progression.⁹⁸ The strongest link between air pollution and cancer incidence and mortality was observed in the Western Pacific Region. This region has documented some of the highest levels of PM_2.5 concentration, with approximately one third of global PM_2.5-related deaths occurring in this area.^99,100

Our meta-analysis confirms the association between air pollution exposure and lung cancer incidence and mortality aligning with the results of other meta-analyses.^{9,25-27,49,96,101,102} The association between PM_2.5 and lung cancer mortality exhibited a greater strength than that between PM_2.5 and lung cancer incidence. PM_2.5 is known to substantially contribute to cancer-related morbidity and mortality, accounting for 14.1% of all deaths because of lung cancer in 2017.¹⁰³ While we did not find a specific association between O₃ and lung cancer incidence and mortality, there is a growing concern regarding the potential health risks of ozone, particularly in light of efforts to control other major air pollutants. In China, for example, research has shown that exposure to a combination of ozone and particulate matter can increase the incidence of lung cancer among females.¹⁰⁴

The study estimated a nonsignificant association between air pollution and nonlung cancer incidence, contrasting the findings by Kim et al,¹⁰⁵ who observed a significant association between PM_2.5 and PM₁₀ exposure and nonlung cancers. Traffic air pollutants, including NO₂ and NOx, have been notably associated with increased breast cancer incidence.^106-108 Air pollutants can potentially influence the occurrence of breast cancer by raising breast density, a recognized risk factor.¹⁰⁹ Identical to our meta-analysis results, Gabet et al¹¹⁰ noted a weak association between PM_2.5, PM₁₀, and breast cancer. Despite low heterogeneity in the identified studies and using a fixed-effect model, we could not establish an association between air pollution and urinary bladder cancer incidence. Similarly, a systematic review by Zare Sakhvidi et al¹¹¹ reported a suggestive positive association (nonsignificant in most studies) between air pollution and renal and urinary bladder cancer incidence.

PM_2.5 and PM₁₀ exposure was significantly associated with breast cancer mortality, synonymous with other meta-analysis findings.^112,113 Similarly, a significant association between PM_2.5 and liver cancer mortality was established in the present analysis. PM_2.5 can trigger oxidative stress, inflammation, and genotoxic effects and expedite liver inflammation and steatosis, which contributes to the initiation and advancement of liver cancer.¹¹⁴

Our meta-analysis supports the hypothesis that exposure to air pollution is significantly associated with cancer incidence and mortality and substantially attributed to PM_2.5. Efforts to mitigate exposure to air pollution can be contemplated on multiple levels, encompassing individual, community, industrial, and broader regional scales. Across various higher-income and select middle-income nations, implementing multiple interventions spanning extended periods has enhanced outdoor air quality and, subsequently, positive impacts on health. Individuals can contribute to environmental well-being by opting for public transportation, cycling, or walking whenever feasible. In addition, using energy-efficient electrical appliances and refraining from burning leaves, garbage, and other materials are effective measures at the personal level. Initiatives to involve communities in tackling air quality include air quality monitoring and conducting environmental or health evaluations in cooperation with stakeholders from professional or policy realms. Adopting an airshed perspective in the management of air quality, involving consideration of a geographic area characterized by a distinct air mass, shared topography, meteorologic conditions, and climate, is found to be beneficial for improving air quality. Enacting laws to establish air quality standards is crucial in mitigating the effects of air pollution on both the public and the environment. Air quality regulations must adhere to a strong governance framework grounded in scientific insights with well-established criteria for accountability, monitoring, and transparency in implementation. While there have been indications of the potential effects on cancer survival after diagnosis, additional research is needed to assess the influence of reducing outdoor air pollution exposure at the patient level on survival outcomes. The meta-analysis results could contribute to community cancer prevention and diagnosis and help inform stakeholders and policymakers in decision making.

Our meta-analysis incorporated a substantial number of participants, with approximately 88,532,011 respondents, which ensured adequate statistical power. We included studies from diverse geographical regions, encompassing a comprehensive range of data. Most studies examining cancer incidence were deemed to have a low risk of bias, thus minimizing the potential for bias to affect the conclusions. Moreover, most studies evaluating cancer incidence and mortality had a Newcastle-Ottawa Scale score of seven or higher. Subgroup analysis was conducted on the basis of various factors such as study design, sex, geographical area, and study quality. Notably, our research went beyond previous studies by investigating the impact of air pollution on the incidence and mortality of nonlung cancers. This meta-analysis, to our knowledge, provides the most recent comprehensive information on the association between significant air pollutants and cancer burden. However, it is essential to acknowledge certain limitations of our study. We observed considerable heterogeneity, as the Higgins I² values indicated, which could introduce variability into the findings. In addition, there was a lack of studies from the Southeast Asia region, limiting the generalizability of the results to that specific area. Furthermore, some cancer subgroups, such as pancreatic, liver, and urinary bladder cancers, were represented by only one or two studies, which may affect the robustness of the conclusions in those specific cases.

AUTHOR CONTRIBUTIONS

Conception and design: Thilagavathi Ramamoorthy, Anita Nath, Shubhra Singh, Prashant Mathur

Collection and assembly of data: Thilagavathi Ramamoorthy, Anita Nath, Stany Mathew, Apourv Pant, Gurpreet Kaur, Shubhra Singh

Data analysis and interpretation: Thilagavathi Ramamoorthy, Anita Nath, Shubhra Singh, Apourv Pant, Samvedana Sheela, Krishnan Sathishkumar

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/go/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Acknowledgment

We are grateful to Dr P.C. Gupta: Healis, Mumbai; Dr Anju Sinha: ICMR, New Delhi; Dr Sreekumaran Nair: JIPMER, Puducherry; and Dr Harshal Salve: AIIMS, New Delhi, for their expertise and assistance throughout all aspects of this study.