A Meta-Analysis of Induced Abortion, Alcohol Consumption, and Smoking Triggering Breast Cancer Risk among Women from Developed and Least Developed Countries

Background The most prominent form of cancer in women is breast cancer, and modifiable lifestyle risk factors, including smoking, alcohol consumption, and induced abortion, can all contribute significantly to this disease. Objectives This study's primary purpose was to assess the prevalence of breast cancer among women in developed and developing countries and the association between three modifiable hazard factors (induced abortion, smoking behavior, and alcohol use) and breast cancer. Methods This study performed a systematic literature database review up to September 21, 2021. We employed meta-analytic tools such as the random effects model, forest plot, and subgroup analysis to conduct the research. Additionally, we conducted a sensitivity analysis to assess the influence of outliers. Results According to the random effects model, smoker women have a higher risk of developing breast cancer from different countries (OR = 1.46; 95% CI: 1.08–1.97). In the case of induced abortion, the pooled estimate (OR = 1.25; 95% CI: 1.01–1.53) indicated a significant link between abortion and breast cancer. Subgroup analysis revealed that smoking substantially influences breast cancer in developing and developed countries. Breast cancer was more common among women who smoked in developed countries than in developing nations. Conclusion The observed findings give sufficient support for the hypothesis that smoking and abortion have a significant influence on breast cancer in different nations. Health organizations should individually design comprehensive scientific plans to raise awareness about the risks of abortion and smoking in developed and developing countries.


Introduction
As the most commonly diagnosed neoplasm, breast cancer is a leading cause of cancer-related mortality among females in both developed and less developed nations [1,2]. Cancer has spread to the majority of countries (154 out of 185) and is currently the primary cause of cancer-related deaths in more than 100 nations [3]. In conformity with the global cancer statistics for 2018, about 2.1 million recent cases, representing nearly one of every four women, were diagnosed with breast cancer. Approximately 626,679 women died due to breast cancer in 2018 [4]. Te incidence (number of new cases occurring or rate per 100,000 persons per year) is highest in developing countries, which account for 60% of the deaths, yet it is growing at a faster pace in middle-and low-income countries [5,6]. More specifcally, most occurrence rates are detected in many European countries, notably Switzerland, Italy, and U.S. whites, whereas rates are low in South America, Asia, and Africa [7]. Te incidence rate for women living in developed countries (except Japan) is four times higher than that of the least developed countries [8,9]. A risk factor is defned as an element that increases the probability of inciting breast cancer [10]. In this way, the identifcation of modifable breast cancer risk factors has crucial implications for preventing and reducing the incidence of breast cancer [11]. Physical activity, diet, weight, use of oral contraceptives, alcohol, ingestion of smoke, anxiety, and stress are conventionally modifable risk factors [12]. Alcohol consumption and smoking are modifable infuencing factors that are generally related to breast cancer to a few more extensive degrees [13,14]. Besides, it is grounded that full-term pregnancy (without abortion or miscarriage) consummately recommends a defensive impact on the possibility of breast cancer. In contrast, the idea of incomplete pregnancies afecting the risk of breast cancer remains ambiguous [15]. Various articles have explored the association between alcohol consumption, smoking intake, induced abortion, and breast cancer [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Previous research suggested an association between alcohol consumption and breast cancer [16][17][18][21][22][23][24]. Moreover, it is evident that multiple studies have found a possible link between smoking and breast cancer [25,29,32,33]. Alcohol causes approximately 4% of breast cancer cases in developed nations [32]. Numerous research studies have suggested a benefcial relationship between breast cancer and induced abortion. Regardless of the alarmingly high frequency of breast malignancy and prompted abortion, the past forty years have delivered neither agreement of opinion into the clinical research nor a need to keep moving to show up at one. Nevertheless, several studies have shown an inverse, null, or weak association between breast cancer and these risk factors (alcohol consumption, smoking intake, and induced abortion), leading to inconsistent fndings [15, 18-20, 26, 34-40]. It may be owing to the short sample size and methodological constraints [36]. Moreover, biases, especially those connected with the case-control studies and the insufcient alternative of the reference group, can produce conficting results on induced abortion and breast cancer [41]. Te literature review reveals that the association between three lifestyle-related variables (such as abortion, alcohol consumption, and smoking) and breast cancer varies between studies. Te generalization of lifestyle-related indicators' infuence on breast cancer among women is pivotal in light of their clinical signifcance, although it is scarce in the literature. To overcome this gap, the primary aim of this study is to apply a meta-analysis based on a comprehensive review of observational studies published by 2021. Tis study elucidates the degree of association between these three attributes and breast cancer among women from least developed and developed countries.
We considered literature in the present investigation based on the following criteria: (a) bivariate data available for the breast cancer risk with alcohol consumption, smoking infuence, and abortion cases; (b) article full-text availability; (c) information made available in the English language; and (d) peer-reviewed, accepted, or published articles. Te authors evaluated the appropriateness of the studies after fnding the full texts. In the case of multiple studies in one country, the data of individual variables were appropriately merged.

Study Selection and Data
Extraction. Te following criteria for including diferent studies were identifed in accordance with the PICOs acronym: Population: women with breast cancer. Intervention: consider three lifestyle-related indicators (e.g., abortion, alcohol consumption, and smoking) of developing breast cancer. Comparison: consider three lifestyle-related indicators (e.g., abortion, alcohol consumption, and smoking) of developing breast cancer. Outcomes: breast cancer, mammary neoplasm, breast neoplasm, breast tumor, mammary cancer, breast carcinoma, and mammary carcinoma. Study design: prospective study, cross-sectional study, cohort study, and case-control study.
Initially, 895 articles were appended after employing distinct search strategies and PICOs schema for each database. In the fnal stage, the authors rechecked and rescanned the abstracts of the included papers to ensure their accuracy. Figure 1 depicts the overall eligibility requirements of the studies for the fnal assessment.

Statistical Analysis.
We have applied the software R version 3.6.2 (Bell Laboratories, New Jersey, USA) and IBM SPSS version 27 (SPSS Inc., Chicago, USA) to convey the investigation. We utilized meta-analysis to examine studies from diferent countries. Computing values evaluated heterogeneity using the p values and I 2 of the datasets [42,43]. We performed the meta-analytical procedure by executing a random-efects model as this study found signifcant heterogeneity, which assessed DerSimonian and Laird's pooled efect [44]. Te Q statistic, a weighted squared deviation, is used to estimate I 2 , and the value ranges from 0 to 100% [45] to display the 95% confdence interval, summary measure, and weight for each article for the most signifcant factors [46]. A leave-one-out sensitivity analysis was conducted to determine the efect of heterogeneity and outliers [47]. We utilized the odds ratio for the summary measures, and all outcomes were weighted to handle bias due to underselection and overselection [48]. For the dichotomous variable, the odds ratio (OR) as well as efect size were estimated with 95 percent confdence intervals (CI). A contour-enhanced funnel plot is adopted for the assessment of publication bias. We have observed the symmetry of the plot to determine whether there is a presence or absence of publication bias. In addition, Egger's test was used to estimate the risk of publication bias, with p values of 0.05 indicating the occurrence of publication bias [49].

Variables.
In this meta-analysis, we well-thought-out breast cancer as the dependent variable. In addition, Egger's test was used to estimate the risk of publication bias, with p values of 0.05 indicating the occurrence of publication bias. We also considered the impacting factors of alcohol consumption, smoking, and abortion cases included as covariates to execute the exploration and fnd out the most impacting factors around the world. Table 1 represents the baseline characteristics of diferent selected studies focusing on smoking, alcohol consumption, and induced abortion triggering breast cancer among women of diferent countries. Table 2 shows the output of the heterogeneity test for alcohol consumption. Te estimated value of tau square is 0.25, which indicates the absolute estimated value of the between-study variation. From the value of I 2 , we have come to know that 95.2% of the overall variation is due to true heterogeneity (which can be explained). Also, the observed weighted value of S.S. is 456.00 with df � 22 and p value <0.001, thus signifcant. Table 2 shows that the pooled estimate is 0.9401 and the 95% confdence interval is [0.751; 1.176]. Tis outcome suggests that alcohol consumption has no signifcant impact on breast cancer in diferent studies in diferent countries. Table 3 shows the output of the heterogeneity test for smoking infuence. Te estimated value of the tau square is 0.55, which indicates the absolute estimated value of the between-study variation. From the value of I 2 , we have come to know that 98.8% of the overall variation is due to true heterogeneity (which can be explained). Also, the observed weighted value of S.S. is 1930.79 with df � 24 and p value <0.001, which is signifcant.  Figure 2 shows the vibrant sight of the random efects model for variable smoking. Inclusive concise information on data from individual studies is given there. We can perceive individual studies' confdence intervals and estimated values with a rectangular shape and combined efects with a diamond shape. Te combined efect for the fxed efects model is 1.27, and for the random efect, the model is 1.46. Te overall visualization of the studies suggests that smoking signifcantly impacts breast cancer in diferent studies. Table 4 shows the output of the heterogeneity test for abortion cases. Te estimated value of tau square is 0.18. It indicates the absolute estimated value of the between-study variation. From the value of I 2 , we have come to know that 84.7% of the overall variation is due to true heterogeneity (which can be explained). Also, the observed weighted value of S.S. is 117.96 with df � 18 and p value <0.001, which is also signifcant.  Figure 3 shows the vibrant sight of the random efects model for the variable abortion case. A comprehensive summary of the data from individual studies is given there. We can perceive individual studies' confdence intervals and estimated values with rectangular and combined diamondshaped efects. Te combined efect for the fxed efects model is 1.13, and for the random efects model, it is 1.25. Te overall visualization of studies suggests that abortion cases signifcantly impact breast cancer in diferent studies. Table 5 represents that the cases of abortion and smoking have a substantial infuence on breast cancer in developing and developed countries. Women who had abortions in developing countries were more likely to have breast cancer (OR: 1.39, p < 0.01, I 2 � 90%) compared to women in          (Figure 4). Besides, the odds of having breast cancer were higher among smoker women residing in developed countries (OR: 3.66, p < 0.01, I 2 � 87%) than in women who smoked in developing countries ( Figure 5). At the 5% level of signifcance, Egger's test for a regression intercept produced nonsignifcant p values of 0.3694 (smoking) and 0.0884 (abortion). It implies that there is no asymmetry in the funnel plot, which is compatible with the absence of publication bias. Terefore, the funnel plots depicted in Figures 6 and 7 show no evidence of publication bias.

Discussion
Te purpose of this study is to systematically identify the degree of association between three lifestyle-related indicators (e.g., abortion, smoking, and alcohol consumption) and breast cancer risk in women in developed and least developed countries. Based on a systematic review of observational studies published in 2020 in PubMed, Wiley, and ScienceDirect, the study was analyzed. According to the author's best knowledge, this is one of the frst studies to execute a meta-analysis of tracking breast cancer risk using three lifestyle-related indicators. Te random efects model in the meta-analysis found that exposure to smoking and abortion was signifcantly related to the chance of developing breast cancer.
Women who smoked had a 45 percent greater likelihood of having breast cancer than women who did not smoke.
Smoking appears to raise the chance of developing breast cancer in both developed and developing countries. Te positive relationship between smoking and breast cancer that was discovered in the present studies was consistent with previous research [50][51][52][53]. Te increased risk of breast cancer associated with smoking could be responsible for the impaired metabolic and immune systems compared to nonsmokers. For instance, a previous study mentioned that tobacco smoke had a substantial adverse infuence on endocrine function [50]. Tis might have also contributed to having worse steroid-responsive tissues and a decreased rate of endometrial neoplasia, accounting for smoking as a human carcinogen.
Individuals with a history of abortion were also found to have an increased chance of developing breast cancer. A meta-analysis reached a similar conclusion, indicating that abortion increases women's risk of breast cancer [54]. Earlier studies that support this assertion have also found a statistically signifcant relationship between abortion and breast cancer risk [55,56]. Contrary to this fnding, two recent studies showed that women who do abortions have no infuence on developing breast cancer [57][58][59]. Te confict could be due to variations in the environment, information, methodology, and so on. Te precise data for abortion is arduous to gather as it is a very private incident for every individual. Terefore, it is argued that the combined efects of several articles increased the validity and accuracy of the present study fndings.
In keeping with the fndings of past systematic reviews, this investigation found no statistically signifcant relationship between alcohol use and breast cancer risk [60,61]. Te underreporting or absence of alcohol consumption in religious countries is one of the key factors  [62,63]. Arguably, the inconsistency may be explained by the prevalence, dose, and type of alcohol consumption due to its non-normative patterns [61,64]. Tus, because the present study used the most recently published articles, the infuence of diverse alcohol consumption incidents varied from country to country. However, some biological factors are correspondingly impactful in this regard. Terefore, further research is required on a large scale to identify the efects of diferent types of alcohol consumption and treatments on breast cancer risk. Tis current study also includes a subgroup analysis to demonstrate the efects of abortion and smoking on breast cancer in developing and developed countries. Te risk of breast cancer is greater across developing territories because of abortion than in developed countries, consistent with an earlier study [65]. Te nonutilization and unavailability of   International Journal of Clinical Practice 9 contraceptives among women in developing countries are observed, which increases the abortion rate [66]. Terefore, this discrepancy occurs due to birth control awareness restrictions in developing and developed settings. Besides, smoking is a sensitive factor in breast cancer in developed countries compared to developing countries. A study conducted with data from 187 countries similarly reveals that smoking infuences breast cancer [67]. Te possible reason might be that antismoking laws like MPOWER measures are not strictly followed in developed countries, provoking the increased possibility of smoking [68].
Smoking and abortion are two risk factors for breast cancer among women in developed and least developed countries, as shown in the present study. Strengthening the implementation of MPOWER policies might help create awareness among women about the hazards of smoking. In addition, multifaceted interventions like government, nongovernment, and NGO's health programs based on sexuality education, unintended pregnancy awareness, and efective contraception and emergency contraception are needed to reduce abortion in society, thus controlling the risk of breast cancer. Besides, comprehensive science-based strategies for developed and developing countries might be designed individually to create awareness about the risks of abortion and smoking.
Tus, smoking and induced abortion are connected with breast cancer in diferent nations, which has clinical signifcance. Its explication will aid health organizations and stakeholders in establishing comprehensive scientifc plans to promote awareness about the risks of abortion and smoking in women. Tis agreement is supported by the extant literature [69,70]. A study on breast cancer patients determined that awareness of the benefts of quitting smoking is related to a reduction in breast cancer severity [69].

Strength and Limitation
Tere are numerous unique strengths in the present study. Firstly, the methodology is the main advantage, as the systematic reviews combine fndings from several published studies and draw a pooled conclusion from them. Secondly, this study considered three exposures to identify their  International Journal of Clinical Practice relationship with breast cancer risk. Tirdly, subgroup analysis appends an additional advanced dimension to the current study. Te current study is not without limitations. Firstly, the methodology follows observational trials that restrict the nature of the generalizability of the study fndings [45]. Secondly, the unavailability of factors such as genetic factors or family factors was not appended, which might contribute to the risk of breast cancer. Additionally, underreporting or the absence of alcohol consumption in religious countries could introduce bias into the study.

Conclusion
Initially, the risk of breast cancer was not associated with smoking-related cancer. Over time, however, sufcient evidence has accumulated to suggest that smoking is correlated with an increased risk of breast cancer. Although this study found no correlation between drinking and breast cancer, it did fnd a substantial association between induced abortion and breast cancer. Tis study reveals that the risk of breast cancer linked to smoking is higher in developed nations than in developing countries. So, the authority should consider these infuences and make their strategies to raise awareness accordingly among people to reduce the smoking habit for a better healthcare situation in their respective countries.

Data Availability
Te data supporting the fndings of this study are available from the corresponding author upon request.

Conflicts of Interest
Te authors declare that they have no conficts of interest.