1. Background
Human and only human is an absolute creature with all materialistic and spiritual features. In His holy verses (Alhijr, 10) (1) God recognizes human beyond the mere physicality by fashioning him from soil and then breathing His spirit into him. He puts upon his shoulder nothing but to serve Him (Zaryiat, 56) (1) which in fact is a responsibility on manās spirituality through his physicality. Humanās spiritual and physical dimensions are interwoven in his creation and inseparable till death takes them apart. Motahari (2) refers to this as spirituality and physicality inter-affecting one another. During the last two decades, there have been spiritual/religious interventions in cancer patients to prevent or treat a range of physical problems, including managing chronic pain, coping with the disease, boosting hope, increasing quality of life and mental health. Koenig (2012) showed, in his review, a fundamental change in studies related to spirituality and religion from 1971 to 2012 (e.g. from 2002 to 2012, the number of studies investigating various effects of spirituality on physical and mental dimensions was 7-fold those of the last 30 years) (3). Spirituality is a universal keyword and representative of search for meaning, perfection and salvation (4). Although societies are of different faiths and belief systems, what they all share is spirituality (5). Of these, some do not differentiate between religion and spirituality, some differentiate the two, some recognize spirituality as part of religion and some others lean toward religion as the basis (6-12). Spirituality is often known in relation with their inner motivations and their emotional relationship with their god(s) (13). While other societies have not yet reached a consensus on the common definition of spirituality (14), Islamic sources have a clear definition for spirituality. To put it in Motahariās terminology, spirituality in view of Quran is the basis for perfection, and it is mostly faith in God and right deeds and behavior or in other words: serving God. In the main study, which is the first one of its kind in the world, conducted by the authors on these very principles, we managed to revive spiritual behaviors in a group of cancer patients leading to changes (the cell biological changes begin with changes in its genes) in their gene receptor expressions so much that genetic stress factors were controlled and the patients were able to experience significantly calmer and more peaceful (15). This is due to the fact that, based on a literature review, with chronic stress, dopamine concentration increases leading to an inhibitory effect on T-cells which in turn expands cancer (16).
2. Objectives
The present study is also an attempt to show the effects of spiritual intervention on gene receptor expressions and behavior modifications in patients based on Islamic principles. The decision stems from causality rules as the main religious guideline of the authors. This is clearly reflected in a Hadith by Imam Sadegh, Peace be upon him āGod refrains from running affairs but by their causes. Thus He has appointed a cause for any effect, an expression for any cause, knowledge for any expression and a way for acquiring any knowledge.ā Upon this, we put forward the hypothesis of changes in gene receptor expressions as a last terminal biological result of spiritual intervention.
3. Materials and Methods
3.1. Participants
58 women suffering from primary breast cancer took part in this study based on inclusion and exclusion criteria and were placed in two groups: experimental and control, with 28 and 29 people respectively. Blood samples were collected prior to and after the intervention to analyze the changes in dopamine gene receptor expressions.
3.2. Concepts
In order to administer the spiritual intervention backed by Quran, Islam and international standards, issues, with emphasis on peace, human growth and perfection, accepting God as an eternal source of power and kindness to build trust and reduce stress, were selected. They included prayer, patience, reliance, self-sacrifice and forgiveness, altruism and kindness, remission and repentance, thankfulness, mantra, meditation, and death concept.
3.3. Structure
The mentioned spiritual issues were presented in 10 weekly sessions of 90 minutes each. The framework of a given session is presented in the following Table 1.
Table 1.Framework of a Given Session
| Session | Spiritual Issue |
|---|---|
| Prayer in the beginning, in order to establish a spiritual presence and to feel closer to God. | |
| Relaxation | |
| Review of material from the previous session as well as the homework | |
| Explanation of the topic at hand for the session with participation of members | |
| Discussion of the topic at hand by members using spiritual/religious and Islamic issues | |
| Summarizing and conclusion | |
| Homework | |
| Ending the session by prayer | |
| Personal consultation | |
| Transcribing discussed topics |
3.4. Procedure
Thus blood samples were obtained from healthy people as controls. Blood samples were obtained from breast cancer patients prior to and after the spiritual intervention as the case group by means of real-time PCR in order to assess the dopamine gene receptor expressions. Participants attended the study with a background of belief in Islam, thus Islamic issues can be explained separately in sessions.
3.5. Prayer
Prayer is an expression of indigence before God when one is desperate of other sources. In other words, āThose who believe, and whose hearts find satisfaction in the remembrance of Allah: for without doubt in the remembrance of Allah do hearts find satisfactionā (Rad, 28) (1). Another verse emphasizes the necessity, āSay [to the Rejecters]: āy Lord is not uneasy because of you if ye call not on Himā, God says, āCall on Me; I will answer your [Prayer]ā (Ghafir, 60) It should be noted that prayer cannot replace efforts and hard work, but rather it completes them. Imam Ali says, He who prays and does nothing else is shooting an arrow without the bowstringā (17). Therefore, we did not replace any of conventional treatments with spiritual factors, but we used it as a useful complementary treatment.
3.6. Patience
āseek help with patient perseverance and prayerā (Baqarah, 153) (1). Although God clearly states, āverily We have created man into toil and struggleā (Balad, 4) (1), yet He advises man to patience repeatedly (e.g. Bagharah, 131 (1)) and adds, āO ye my servants who believe! Fear your Lord, good is [the reward] for those who do good in this world. Spacious is Allahās earth! Those who patiently persevere will truly receive a reward without measure!ā (Zummar, 10) (1).
3.7. Reliance
It is relying on someone else for your affairs; admitting weakness and ignorance, one relies on a qualified, trustworthy source of wisdom (18). Quran reassures people that the relation between reliance and faith is undeniable and guarantees its effectiveness (Maida, 11 and 23; All-i-Imran, 122 and 160; Anfal, 49; Abraham, 11; Tauba, 51; Mujadilah, 10) (1). Imam Ali says that faith has four pillars: reliance on Allah, assigning affair to Allah, satisfaction with His will and obedience to His orders (19). Allah says, āAnd if any one puts his trust in Allah, sufficient is [Allah] for him.ā(Talagh, 3) (1).
3.8. Alms
People give alms to purify and sanctify themselves (Tauba, 103) (1). Those who give in charity will have their rewards with Lord (Bagharah, 274) (1) , will please Him, be free of fears and be bestowed by His blessings (Al-i-Imran, 180) (1). āThe parable of those who spend their substance in the way of Allah is that of a grain of corn: it groweth seven ears, and each ear Hath a hundred grains. Allah giveth manifold increase to whom He pleaseth: And Allah careth for all and He knoweth all thingsā (Bagharah, 261) (1). āThose who spend [freely], whether in prosperity, or in adversity; whorestrain anger, and pardon [all] men;- for Allah loves those who do goodā (All-i-Imran, 134) (1).
3.9. Altruism and Kindness
Loving others is a key concept in holy Quran. The first verse of Quran, āIn the name of Allah, Most Gracious, Most Mercifulā, is a manifestation of mercy and love. Faith and love are inseparable. God says that those who have faith, love God more. As human goes further on the path of faith, he falls deeper in love with his goal and finds more pleasure (20). āOn those who believe and work deeds of righteousness, will [Allah] Most Gracious bestow loveā (Maryam, 96) (1). That is to say kindness generates kindness as God says to the holy prophet Muhammad, āIt is part of the Mercy of Allah that thou dost deal gently with them Wert thou severe or harsh-hearted, they would have broken away from about thee: so pass over [Their faults], and ask for [Allahā] forgiveness for them; and consult them in affairs [of moment]ā (Al-i-Imran, 159) (1).
3.10. Repentance
Repentance is a meaningful relationship that keeps people closer to God, those who were on the path to part from Him. Repentance is the most effective measure to seek spirituality that is knowing God and right deeds. God speaks of these in various verses (Al-i-Imran, 135; Nissa, 110; Hood, 11; Tauba, 27; Shuaraa, 13 and 25; Anam, 54) (1). The key point here is that repentance is not accepted in defiance and rejecting (Al-i-Imran, 90 and 92) (1). Thus this component brings about prerequisites one needs to reform oneself and get closer to God.
3.11. Thankfulness
Thankfulness means using Godās blessings in the way they were aimed at their creation. Thankfulness is key to grace and value of self, and attracts people onto God. God Himself is thankful and appreciated those who give (Tagabun, 17) (1) and He says, āIf ye are grateful, I will add more [favors] unto youā (Abraham, 7) (1); āAny who is [so] grateful does so to the profit of his own soulā (Luqman, 12; Bagharah, 56) (1).
3.12. Mantra
Mantra (zikr) is the remembrance God in a devotional act and admitting His presence to meet human needs, and with it comes satisfaction and peace, āfor without doubt in the remembrance of Allah do hearts find satisfactionā (Rad, 28) (1).
God says, āO ye who believe! Celebrate the praises of Allah, and do this oftenā (Ahzab, 41) (1) and says, āBut whosoever turns away from My Message, verily for him is a life narrowed downā (Ta Ha, 124) (1). āThe most beautiful names belong to Allah: so call on him by them; but shun men as use profanity in his names: for what they do, they will soon be requitedā (Araf, 180) (1).
3.13. Meditation
It is the most effective way in reforming oneās behavior and persistence of right deeds. (Maida, 105) (1). Prophet Muhammad did emphasize on weighing oneās deeds. Meditation causes rectifying mistakes and timely correction of deeds and behaviors.
3.14. Death Concept
Death, the most certain incidence in life, is the most complicated concept. But Islam and psychology agree that emotional reactions of people to death and accepting death highly depend on their deeds, behaviors, thoughts, personality, and coping capabilities. God created death and puts it ahead of life (Mulk, 2) (1); He does not know death as the end of life but rather a new beginning (Zumar, 42; Waqia, 60; Anbyia, 34) (1). God brings the dead to life and this is one of His signs (Yunus, 56; Bagharah, 73) (1). Imam Sajad peace be upon him says, ādeath to believers is like ridding themselves of filthy and ragged clothes filled with bugs, and breaking free of heavy chains and shackles; instead change into scented elegant clothes, tamed horse and glorious houses. Or it feels like sleep only much longer (21).
Bearing in mind the religious/Islamic factors mentioned above, we designed a 10-session intervention of 120 minutes each session with āto do at home exercisesā in order to revive and re-establish the spiritual concepts within individuals. Every session would begin with prayer and then information on definition, cognition, and experience of the mentioned concepts were elicited in form of questions. The therapist(s) would then continue with follow-up questions to later establish the concepts upon the responses. Homework was assigned to participants based on the established concepts which were reviewed in the following session to address possible questions. Then blood samples were collected from the healthy individuals as control group, and from cancer patients as the case group both prior to and after the intervention. Gene expressions were measured and studied by real-time PCR.
4. Results
Obtained results, as thoroughly explained in our previous study (15), from peripheral blood mononuclear cell samples analyzed by Real time-PCR collected from patients who underwent the conventional treatment together with the spiritual intervention showed significant reduction in dopamine gene receptor expressions in comparison with those of pre-test scores and the control group (Tables 2 and 3).
Table 2.Experimental Group Peripheral Blood Monocle (PBMC) Pre-Test Scores Compared to Post-Test Scores
| Dopamine Receptors | Rate of Change | Standard Error | P Value |
|---|---|---|---|
| 9.81 | Ā± 1.70 | 0.001*** | |
| 8.11 | Ā± 0.89 | 0.001*** | |
| 8.56 | Ā± 0.97 | 0.001*** | |
| 6.94 | Ā± 0.73 | 0.001*** | |
| 2.56 | Ā± 0.63 | 0.004** |
a*** Significant decreasing at P ā¤ 0.001 level (down regulation), ** Significant decreasing at P ā¤ 0.01 level (down regulation), and * Significant decreasing at P ā¤ 0.05 level (down regulation).
Table 3.Experimental Group PBMC Compared to PBMC in Control Group
| Dopamine Receptors | Rate of Change | Standard Error | P Value |
|---|---|---|---|
| 8.61 | Ā± 0.84 | 0.001*** | |
| 10.73 | Ā± 0.77 | 0.001*** | |
| 11.8 | Ā± 1.0 | 0.001*** | |
| 8.90 | Ā± 0.7 | 0.001*** | |
| 3.7 | Ā± 0.73 | 0.004** |
aSee footnote of Table 2.
5. Discussion
Cancer is known as the major health threat of the century given rise to by inadequate nutrition, rising life span average, lack of physical activities, smoking, drinking alcohol, and chronic stress (22). Interventions to control causes of cancer are typically educational based programs to raise awareness resulting in changes in patientsā behavior. However, to come to terms with stress factors and to control chronic stress, there are various solutions, mostly psychological ones. Many are the studies reporting the positive effects of psychological interventions in reducing stress, depression and better coping with physical-psychological damages (23, 24). Spiritual interventions have been shown to generate positive effects in fighting against physical problems caused by cancer including chronic pain, fear of death, hope and mental health (25-28). Chronic stress manipulates the immune system through changes in catecholamine and cortisol release and eventually results in a reduction in protective cells especially T-cells activities (29). It also brings about lower quality of life, disruption in mental health, reduction of hope, and increase in anxiety and depression (30, 31). Spiritual interventions have been able to generate positive outcomes in all these cases (32-34) and based on previously mentioned verses, (e.g. surely in the remembrance of god do hearts find rest (Rad, 28) (1)), they could reduce chronic stress.
The authors of this study designed a spiritual intervention for the first time in the world based on the philosophy of causality and based on a Hadith from Imam Sadigh, āAllah doth everything in its natural way by means of known causesā (21), to discover the changes in dopamine gene receptor expressions as the final result of biological effect of spirituality. These manipulations generated direct effects in reducing chronic stress as well as cell proliferation (35, 36). There are important neurotransmitter pathways in the neuroendocrine system that control secretion of other neurotransmitters, like dopamine, serotonin, glutamate, etc. And they can play roles in causing or treating diseases via their interaction with other systems (37). Dopamine receptors and transmitters functioning in nerves have the capability to indirectly predict diseases or even worse directly cause diseases (37). In a study by Terasaka et al. conducted in 2000, they showed the reducing effects of dopamine (dose dependent) on the number of living cells in salivary gland tumors and squamous cell carcinoma (38). Also, Gutzkow et al. in a similar study back in 2003 showed that dopamine affects cAMP proliferation in T-cells and hinders their proliferation. Since the link between dopamine and its receptor increases cAMP proliferation, this secondary messenger has a regulatory function in cell proliferation and hinders lymphocyte proliferation (39). Hence a substantial increase in inhibitor receptors can weaken the immune system and in turn affects proliferation and induces spread of the disease. Dopamine is the stress related hormone. cancer patients experience stress from two sources: the chronic stress because of 3 to 5 years prior to cancer, and stress because of cancer and possibility to lose their job, to be socially isolated, to have financial problems, to spend a lot of time in chemotherapy or radiation therapy and the expenses. Therefore, due to the fact that stressful events can weaken the immune system and transform the disease from primary stages of neoplasm growth to higher stages of cancer (40), spiritual intervention can generate peace by reducing stress. As a result, by affecting the nervous system, it can regulate and balance in immune cell receptors (15).
Evidently, if spiritual factors are practiced, they can reduce stress factors and thus cell proliferation by changes in gene receptor expressions including dopamine gene receptor expressions and the consecutive epigenetic changes. Pornour et al. studied changes in dopamine gene receptors in breast cancer patients and healthy subjects and showed that DRD1-DRD4 dopamine gene have increased significantly in cancer patients accompanied by cell proliferation (41). These studies showed that chronic stress had direct effects on dopamine and its impact on recurrence or spreading of the cancer, and that spiritual therapy had positive effects in reducing stress and changing dopamine gene receptor expressions. In this study, we considered verses from the Holy Quran and Hadiths from the holy prophet Muhammd and his successors. In fact, changes in dopamine gene receptors give rise to cell proliferation and the spiritual intervention proved to have anti-cancer effects.
5.1. Conclusion
Spiritual intervention based on Islamic principals can bring back mental health, increase hope and quality of life and eventually change dopamine gene receptor expressions resulting in reduction of cell proliferation, thus better prevention and treatment in breast cancer patients compared to other forms of treatment.
