Introduction

Globally, cancer is the second cause of mortality and the number of cancer patients worldwide is expected to double in the next 50 years [1, 2]. The number of disability-adjusted life years (DALYs) due to all cancer has been gradually rising over the past two decades [3]. 8.97 million deaths were caused by cancer, accounting for 15.8% of all-cause mortality [4]. The growing incidence and burden of cancers in the past decades demands thorough investigation of cancers and the epidemiology of responsible risk factors [5].

The overall impact of environmental risk factors on cancer can be measured by either the number of attributable cancer cases or the number of attributable cancer deaths. Worldwide, it is estimated that around 20% of premature cancer deaths are due to environmental risk factors. In Europe, almost 9% of all cancer deaths in 2019 were estimated to be attributable to this group of risk factors Additionally, environmental risks were responsible for more than 5% of cancer deaths in several European countries [6]. The International Agency for Research on Cancer (IARC) has identified a significant number of modifiable factors, including indoor pollutants from burning coal, as known human carcinogens [7, 8]. About 3 billion people worldwide are affected by indoor air pollution (IAP), which is mostly caused by the use of solid fuels for cooking and heating. This has a significant negative impact on health, including cancers [9]. Although generally environmental risk factors are known to be non-modifiable, the effects of some of these risks could be limited by making changes in the environment and place of living, especially regarding risks like household air pollution which could be significantly controlled by improving in-house fuel used for cooking, heating, or other purposes [10]. These statistics highlight the importance of addressing environmental and occupational risk factors for cancer through evidence-based interventions.

It is crucial to implement strategies that modify behaviors, settings, processes, regulations, and policies to reduce exposure to environmental risk factors, particularly in low middle income countries (LMIC) in which the effect of environmental risk factors on burden of disease is significant, and this major issue is neglected principally in vulnerable groups [11]. By doing so, the prevalence of these risk factors can be reduced, leading to a decrease in the number of future cancer mortality. The population attributable fraction (PAF), which is the percentage of mortality that is attributable to that exposure, can be used to evaluate the public health impact of specific exposures on disease mortality. [12] The PAF is an appropriate epidemiologic measure to be considered by policymakers for prioritizing the preventive strategies and interventions based on the percentage of mortality saved by modifying a risk factor.

In this study, we aimed to calculate the population attributable fraction of environmental risk factors on cancer mortality in a large population-based cohort study with about 18 years of follow up which is settled in a LMIC to provide evidence for policy implication. The main findings of this study were outlining the patterns of predominant fuel use, water source, and animal contact in the cohort study and the share of mortality of each major cancer attributable to the corresponding type of each environmental risk factor.

Materials and methods

Results

Baseline characteristics

From 50,045 participants in Golestan Cohort, 211 of them were diagnosed with cancer when entered the study, which 61 did not have complete information of their disease or of the variables we were investigating, so 49,773 participants of whom 2,196 were deceased from cancer were enrolled in this study. Of all participants, 28,685 (57.56%) were female and 21,149 (42.44%) were male. Most of them 39,866 (80%) lived in rural areas and others 9,968 (20%) lived in urban areas. The vast majority, 41,728 (84.76) used gas as their main fuel for cooking, and as for heating only 5,839 (11.86%) used gas. The main fuel for heating was Kerosene used by 35,486 (72.08) individuals. About 45 percent (22,800) of participant had former contact and 6.72% (3,346) had no animal contact in their life. 8,419 (16.91%) of participants did not have access to tap water source in their life. Gastrointestinal (GI) Cancer patients had the highest mortality with 1,099 deaths after about 18 years of follow up followed by hematologic cancer (166), lung cancer (159), and brain cancer (79). The majority of deceased cancer patients aged between 55 and 64 except for brain cancer which was a decade earlier. Most cancer deaths were reported in male participants particularly, lung and stomach cancer. This pattern is reverse in brain cancer. Mortality of cancer is higher in individuals with low score of wealth among all type of cancer except for colorectal and hematologic cancers. The prominent fuel used for cooking and heating is gas and kerosene in all cancer type, respectively. Biomass use is higher than kerosene use in stomach and esophagus cancer deaths in both cooking and heating purpose, but is in third level in other cancers. Higher amount of former animal contact is reported among stomach and colorectal cancer deaths comparing to other cancer types. More detail could be found on Table 1.

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Table 1. Baseline characteristics Golestan Cohort participants and the demographic and environmental risk factors by cancer type mortality.

https://doi.org/10.1371/journal.pone.0304828.t001

HR and PAF of environmental risk factors on all-cancer mortality

Among indoor air pollution, biomass use in cooking purpose is associated with increased risk of all-cancer mortality with HR 1.17 (95%CI: 1, 1.38) compared to gas. However, other type of fuel for cooking and heating purpose had no association with all-cancer mortality. Of total cancer deaths, 1.26% (95% CI: 0, 2.64) were attributable to biomass use as fuel for cooking purposes.

This means that about 26 deaths from cancer could be prevented if biomass is eliminated for cooking purpose. There was no significant association between animal contact and type of water source as environmental risk factors with all-cancer mortality. There is no significant association found in rural and urban residence between exposures and mortality (Table 2).

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Table 2. The hazard rate and population attributable fraction of environmental risk factors on all-cancer mortality.

https://doi.org/10.1371/journal.pone.0304828.t002

HR and PAF of environmental risk factors on GI cancer mortality

Predominant biomass use for cooking was associated with higher risk of esophageal, gastric and colorectal cancer mortality with HR: 1.66 (95% CI: 1.22, 2.26), 1.37 (1, 1.92), 1.84 (1, 3.42), respectively. There is no association between kerosene use and risk of GI cancer mortality. The estimated PAF for biomass was slightly higher among esophageal cancer 5.70 (1.53, 9.69) comparing to gastric cancer 3.01 (0, 6.45). Eliminating biomass for cooking purpose could reduce about 23 and 13 deaths from esophageal and gastric cancer. Although biomass was associated with higher risk of colorectal cancer mortality, but the respective PAF was not significant. Moreover, no association was found between different type of fuel use as indoor pollution for heating propose and GI cancer mortality. Using non-tap water source is associated with higher risk of esophageal cancer mortality with HR 1.26 (1.00, 1.58), and PAF: 5.01 (0, 10.03), saving about 21 deaths by using healthy tap water source. Hence, there is no association reported with other type of GI cancer mortality. There is no association between animal contact and GI cancer mortality (Table 3).

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Table 3. The hazard rate and population attributable fraction of environmental risk factors on GI-cancer mortality.

https://doi.org/10.1371/journal.pone.0304828.t003

In rural area, biomass use for cooking propose was associated with higher risk of esophageal cancer mortality [HR: 1.69(1.24, 2.30), PAF: 6.36(1.82, 10.70)], gastric cancer mortality [HR: 1.38 (1, 1.93), PAF: 3.43 (0, 7.33)], and colorectal cancer [HR: 1.88(1.00, 3.53), PAF: 6.25 (1.76, 13.63)]. This pattern is not seen in urban area. Moreover, non-tap water source is associated with higher risk of mortality in esophageal cancer [HR: 1.26(1.01,1.59), PAF:5.50(0, 10.93)]. There was no association in urban area between environmental risk factors and cancer mortality. In addition, no association was found between environmental risk factors and pancreatic cancer mortality.

Discussion

This study estimated the population attributable fraction of cancers due to environmental risk factors. The main finding of this study was a significant reduction in cancer-related mortality when biomass fuel, as an indoor air pollution, was replaced with gas for cooking purpose, particularly in GI cancers. Prominent use of biomass for cooking purpose increased 84%, 66%, and 37% the risk of colorectal, esophageal, and gastric cancer mortality, respectively. About 6 percent of esophageal cancer, 3% of gastric cancer, 6% of colorectal cancer mortality would be saved by eliminating non-gas fuel for cooking particularly in rural area. Using healthy piped water source could save 5% of esophageal cancer mortality, particularly in rural area. We could not find any significant association between indoor air pollution for heating purpose or animal contact with cancer mortality. Although, accessing sufficient healthcare facilities and quality treatment is a challenge for those living in rural areas, controlling environmental risk factors could potentially reduce mortality in both rural and urban regions [19].

Indoor air pollution from solid fuels is a major risk of respiratory tract and other organs diseases and cancers, especially when solid fuels are used in poorly ventilated spaces in which toxic emissions from combustion accumulate and increase the risk of diseases [20]. The aforementioned situation of using solid fuels in poorly ventilated places mainly happens in developing and low- and middle-income countries, where poor housing structures exist and solid fuels are still extensively used to heat the living place and for cooking purposes [21]. The contribution of indoor air pollution from solid fuels to lung cancer and other respiratory cancers like those arising from larynx, hypopharynx, tracheal, and bronchus is demonstrated previously [22]. Moreover, in low-income population, biomass smoke is a risk factor for esophageal and gastric cancer [8]. A meta-analysis of literature found higher risk of upper-digestive tract and cervical cancer associated with household air pollution, while the results were adjusted for other risks like smoking [23]. Studies have shown associations between certain types of air pollution and brain cancer [24, 25]. Besides, some studies have reported associations between indoor air pollution from solid fuels and other neurologic conditions and cognitive impairments, which altogether suggests the neurologically toxic impact of the emissions of solid fuels on human brain and neurologic system [26–28]. In this study, we did not observe any impact of indoor air pollution on the mortality rate of brain cancer patients. Among hematologic malignancies, studies reported associations between indoor pollutants of nitrogen dioxide and several types of volatile organic compounds and incidence of childhood acute leukemia [26, 29]. It is suggested that various environmental pollutants added to immunologic factors and genetic susceptibility may expose to leukemia [30, 31]. Parallel to other studies, we observed that the use of solid fuels for cooking purpose had a significant impact on esophageal, gastric, colorectal, lung, and hematologic cancer related mortality particularly in individuals living in rural areas. By implementing appropriate interventions to minimize the application of solid fuel by society, 1% of all-cancer, 6% of esophageal, 3% of gastric, and 6% of colorectal cancer deaths would be averted, adjusted for confounders including socioeconomic status. This has great impact on the burden of cancers in LMIC which are struggling with the health inequities.

According to several studies, there is an apparent excess risk of all-cancer mortality among cities that use surface drinking water supplies, with the increased risk being slight but statistically significant, while the results of recent studies do not appear to implicate drinking water as a factor in causing considerably higher cancer mortality rates in cities, and the gastric cancer mortality rate is higher among those who drink river water than those who drink shallow well water [32–34]. A study by the Environmental Working Group found that millions of Americans are drinking water containing carcinogens, and the contamination may be responsible for more than 100,000 cases of cancer. The strongest evidence for a cancer risk involves arsenic, which is linked to cancers of the liver, lung, bladder, and kidney [35, 36]. In LMIC, the relationship between water source and cancer mortality is not extensively studied. This indicates a gap in research in these regions. However, the available previous evidence suggests that water source can potentially impact cancer mortality rates. This study implemented in a LMIC for the first time suggested association between water source and esophageal cancer, which is parallel to available evidence from developed countries.

Epidemiologic studies to date have provided little evidence that animal viruses and bacteria cause human cancer, although exposure to farm animals or manure has been associated with childhood brain and adult hematologic tumors in some studies [37, 38]. Overall, the available search results do not provide clear evidence on the relationship between animal contact and cancer mortality in humans. This study did not find any association between animal contact and any type of cancer mortality.

Iran, as a LMIC, faced a dramatic change in the burden of cancer and exposure to environmental risk factors in recent years. Exposures like indoor air pollution due to solid fuels have decreased substantially with wide-spread improvements in gas piping system through the country in this period [39, 40]. However, the use of biomass and solid fuels still is the only option in some regions of the country with limited resources [40]. Public health implications of the findings of this study could be focused on the populations with significant exposure to indoor air pollutants due to solid fuels and provide more cancer screening programs for them. Also, continuing efforts to decrease solid fuel use for heating, and cooking especially in settings with limited and inadequate ventilation need to be pursued to handle the burden of cancers associated with the toxic emissions of these sources of energy. To reduce the burden of cancer, it is crucial to implement evidence-based and comprehensive cancer prevention strategies that target modifiable risk factors. These strategies can include public policies, health-promoting environments, personal and community interventions, and optimized health service. By implementing interventions that target these risk factors, it is possible to make significant progress in reducing the number of cancer mortalities [41]. Reducing the environmental risk factors that affect cancer mortality requires a multi-faceted approach [42]. First, allocating sufficient resources by regulations to prevent exposure (including occupational) and reducing pollution. Stakeholders should allocate resources to mitigate or eliminate barriers to reducing environmental cancer risks. Second, changing behaviors can also reduce environmental and occupational cancer risk. Policies should be implemented to provide education and awareness to the public about the environmental risk factors that can cause cancer. This can include information about how to reduce exposure to indoor air pollution and how to identify hazardous substances. Third, providing access to clean water should be implemented to ensure that all populations have access to clean water sources. Fourth, conducting research on the environmental risk factors that can cause cancer. This can include identifying the sources, magnitude, routes of exposure, and distribution of these risk factors. Measuring the potential cancer mortality related to environmental hazard exposure can benefit to update efforts to modify health of communities. Finally, environmental justices are necessary and one of the social determinants of health which is neglected particularly in LMIC. The underprivileged population should be priories in implementation of policies which reduce the unique or compounded health risks. By implementing these policy strategies, it is possible to minimize environmental risk factors that affect cancer mortality and reduce the burden of cancer. However, it is important to prioritize efforts and focus on equity when implementing cancer prevention strategies. This ensures that interventions reach all populations, including vulnerable and marginalized groups, and that resources are allocated appropriately. Timely implementation, focus on equity, and prioritization of efforts are associated with public health and economic benefits. Detecting the level of awareness of cancer risk among high risk groups is essential for achieving health equity. Providing access to screening for people who are medically underserved and have low incomes, studying the cost of preventive care and cancer treatment, and the reasons people may not be able to prevent cancer, early detection, and treatment are other ways to achieve equity.

The strength of this study is its extensive follow-up of a large population based cohort with detailed risk factor assessments, and low rates of loss to follow-up which enable us to calculate precise estimations. Furthermore, this study is among the first to assessing the proportion of cancer mortality attributed to environmental risk factors in a LMIC. However, we could not assess the quantitative markers of indoor air pollution, such as the amount of natural carcinogenic chemicals produced by burning fuel in the household air as the data were not available. In this study, the adjusted Hazard Ratio (HR) was used to estimate Population Attributable Fraction (PAF). however, other variables such as access to facilities, first diagnosis, and treatment may have an impact on the prevalence and hazard ratios. we used socioeconomic status and urbanization as a proxy for health care access as they have correlation, hence, future research should investigate these factors in further studies. Moreover, there are other sources of indoor pollution that were not assessed in this cohort study. Bakhoor and other types of incense pose adverse health effects when used indoors, particularly in locations with inadequate ventilation. These suggested to be considered in future cohort studies.

Conclusions

To conclude, the effect of environmental risk factors is significant with substantial number of cancer mortality attributable to these risk factors. This study found significant associations between certain types of cancers and exposure to indoor air pollution and unsafe water source, based on a population-based cohort study in Iran. GI cancer showed to have strong associations with fuel and water source, especially among rural residents, which are more exposed to solid fuels use in Iran. Adopting appropriate strategies and interventions such as educating population, allocating resources for improving healthy environment of the community, and cancer screening polices among susceptible populations and decreasing exposure to solid fuels is suggested to be adopted by stakeholders and policymaker to reduce cancer mortality.