| Background: The association between psychological factors and diseases has been discussed in traditional Chinese medicine(TCM)theory since ancient times.However,no systematic study regarding this theory has been conducted in the fields of cancer diseases.Objective: The purpose of this study is to investigate the theory regarding the association between psychological factors and cancer diseases in different historical periods,to analyze its theoretical connotation and characteristics,to compare the theoretical similarities and differences among different periods,and to outline the development of theories related to this kind of cancer etiology.With the method of systematic review,the study took the relationship between marital status and breast cancer risk as the object of study to provide evidence for the relationship between psychological factors and cancer.Methods: This research is divided into two parts: The first part examines the theory regarding the association between psychological factors and cancer diseases in different historical periods.We analyzed ancient medical literature that are representative,official and mainstream in each historical period with general research methods.According to the social background of each historical period,the characteristics of medical development,and the academic viewpoints of the main medical experts,we will systematically collate and analyze the data,and probe into the connotation of related theories.The contents of the research and analysis include the types of malignant tumors related to psychological factors,the types of psychological factors,the pathogenic patterns,the key pathogenesis,the influencing factors and other relevant theories.It will be discussed in combination with other psychological theories and the theory of tumor etiology and pathogenesis,if necessary.Additionally,we will compare the theories in different historical periods and outlines the development vein of this theory.The second part is a research of systematic review,exploring the relationship between marital status and breast cancer risk,to provide evidence for the relationship between psychological factors and malignant tumors.The MEDLINE,EMBASE and Psyc INFO databases were searched from their inception to September 2018.The Newcastle-Ottawa Scale was used to rate the methodological quality of included studies.Study data were pooled using random-effects meta-analyses to compare breast cancer risk between unmarried,widowed,divorced or lifelong single women and married women.Subgroup analyses by adjustment level were also performed.Meta-regression was performed when high heterogeneity was detected.This study is registered with PROSPERO(number CRD42018112368).Results: Through analyzing the literature of past dynasties,it is found that the theory regarding the association between psychological factors and cancer diseases has the following characteristics:(1)Anxiety,anger and thinking were the main causes of illness,but joy,fear and surprise were rarely mentioned by ancient TCM practitioners.(2)Psychological factors could become the etiological factors of tumor diseases,only if they meet specific states,such as the abnormal condition with regards of quality,quantity or degree.(3)The common cancers caused by psychological factors mainly include breast cancer,esophageal cancer,thyroid cancer,cervical cancer,lip cancer,tongue cancer,bone cancer,penis cancer.(4)There are four modes of psychological pathogeny in tumor diseases,which are pathogenic mode with single psychological factor,pathogenic mode with multiple psychological factors,pathogenic mode with psychological factors and other factors,and pathogenic mode with psychological factors or other factors.(5)The course of disease is influenced by many factors,such as the change of social and economic level,the special physiological characteristics of certain population,such as widows and nuns,the bad luck of the imperial examination,and the character of being doubtful and unyielding.(6)The key to the occurrence of malignant tumor syndrome caused by psychological factors is the turbulence of the movement of qi,which is mainly caused by qi-stagnation and qi-inversion;the viscera injured mainly involve the heart,liver and spleen;it is often accompanied with deficiency syndrome and fire-heat characteristics.With the development of the dynasties,the knowledge of psychological pathogenic phenomena in tumor diseases has been accumulated,the amount and content of the literature have been increasing and enriching,and the description has gradually changed from general and vague to specific and detailed.Specifically,the theoretical features of each period are as follows:(1)In the pre-Qin period was the embryonic stage,there was no direct discussion about the occurrence of tumor caused by psychological factors,but the scattered psychology medicine seemed to be the embryonic form of the theory regarding the association between psychological factors and cancer diseases.(2)The period of Qin and Han dynasties was the foundation stage,which manifested the obvious view of mind-induced phenomenon in the tumor diseases,such as ji syndrome,blockage syndrome,syndrome of consumption of yinqi and loss of essence and ju syndrome,and laid the foundation for the theory of "five aspirations leading to five ji".But at this time,the understanding of malignant tumors is still at the stage of relatively vague.(3)From the Wei dynasty to the Tang dynasty,through the accumulation and observation of clinical practice,doctors gradually enriched the range of cancers that could be caused by psychological factors From the General Diaphragm Syndrome,ji syndrome and ju syndrome to the five-choke Syndrome,five-diaphragm Syndrome,"ji syndrome induced by deficiency","ji syndrome induced by seven-qi" and shiju syndrome;psychological causes appear directly in the name of the disease,directly linking psychological factors with tumor diseases;the medical literatures not only contain a wide range of diseases,but also list a variety of causes,in which psychological factors and other causes are often in a parallel position.(4)In the Song,Jin and Yuan Dynasties,the theory of mind-induced disease made a creative breakthrough and entered a mature stage.Since the theory of three causes was put forward,later generations of doctors have used this method of etiological classification to penetrate into the understanding of the etiological factors of various diseases,including tumors,and thus psychological factors could play a more important role in the etiology of cancer diseases.In addition,with the deepening of the understanding of the disease,doctors have gradually found some unique characteristics of cancer,and could grasp the main cause of the disease.(5)With the unprecedented development of internal medicine and surgery in the Ming and Qing Dynasties and the Republic of China,the number of literatures related to the psychological causes of tumor diseases also greatly exceeded that of the previous generations.The types of psychological causes and cancer were enlarged obviously,and the perspective that certain cancer diseases could be caused by psychological factors alone gradually became the mainstream in the TCM theory.The relationship between the above psychological factors and the incidence of malignant tumors has also been verified by the method of systematic review.The results are as follows: Forty-seven publications were included in the meta-analysis.Compared with married women,unmarried,divorced and lifelong single women have an elevated risk of breast cancer;the pooled ORs of case-control studies were 1.22(95% CI: 1.07 to 1.39),1.34(95% CI: 1.01 to 1.77)and 1.34(95% CI: 1.10 to 1.63),respectively;the pooled OR of cohort studies examining the effect of being lifelong single was 1.10(95% CI: 1.04 to 1.16);multivariate-adjusted estimates demonstrated a strong association,while age-adjusted estimates produced nonsignificant results.Being widowed was inversely associated with breast cancer risk(OR=0.95;95% CI: 0.81 to 1.12),but the estimate was not statistically significant.Heterogeneity was moderate to substantial across case-control studies(I2: 48% to 82%),which might be partially explained by differences in geographic region and publication year according to the meta-regression.No indication of publication bias was observed in the funnel plot and Egger’s test(P=0.07).However,suboptimal selection of controls,insufficient exploration of confounding effects,and inadequate ascertainment of marital status may have limited the quality of the available evidence.Conclusions: The theory regarding the association between psychological factors and cancer diseases could be traced in almost each dynasty.With the evolution of the dynasties,the knowledge of tumor etiology has been accumulated continuously,and the amount and content of the literature have been increasing and enriching The understanding of etiology gradually changed from generality and ambiguity to concreteness and refinement,the expression of pathogeny became more and more clear,the analysis of pathogenic mechanism became clearer and the records of influencing factors became more and more abundant.Anxiety,anger and thinking were the main causes of illness and the common cancers caused by psychological factors include breast cancer,esophageal cancer,thyroid cancer,cervical cancer,lip cancer,tongue cancer.The key to the occurrence of malignant tumor syndrome caused by psychological factors is the turbulence of the movement of qi,which is mainly caused by qi-stagnation and qi-inversion;the viscera injured mainly involve the heart,liver and spleen;it is often accompanied with deficiency syndrome and fire-heat characteristics.Emotional factors can only become the pathogenic factors of tumor diseases and syndromes when there are abnormity in quality,quantity and degree,which is usually initiated by the stimulation of negative life events and influenced by many factors such as constitution,temperament and personality.It is inferred that the intervention of these influencing factors can prevent the occurrence of tumor to a certain extent,which is proved by the systematic review investigating the relationship between marital status and the incidence of breast cancer. |
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