Laryngeal cancer is a common malignant tumor of the head and neck region, exhibiting an increasing incidence in recent years. The latest data indicated the global standardized incidence rate of laryngeal cancer to be 2.2/100,000 population (1). In China, specifically, the incidence rates in certain provinces have been reported to be ~2.31/10 million (2). However, this rate has increased in recent years. In modern medicine, it is important to consider not only factors such as physical chemical stimulation and pathogenic infection, but also socioeconomic factors, life and dietary habits, personality and psychological behavior (3). The majority of previous studies on laryngeal cancer have indicated that its incidence is associated with smoking, alcohol consumption, lifestyle factors and living environment (4,5). However, a growing number of studies have demonstrated that stress, low social support, community alienation, chronic social isolation, and other related psychological variables, may lead to cancer development (6–8). As medicine has shifted from its reliance on the traditional biomedical model to a more multidisciplinary biological-psychological-social model, the profound impact that social psychology has on cancer risk, development and outcome, has become more apparent (5). Psychosocial factors refer to life events, coping mechanisms, social support and personal traits, among others. Through retrospective and prospective research, national and international studies have discovered that long-term and chronic stress and stressful life events may increase the risk of various tumors, such as breast (7,9), prostate (10) and colorectal cancer (11). A 1:1 matched case-control study was conducted, involving 237 laryngeal cancer patients and healthy controls, in order to expand on these findings and provide evidence for the improvement of laryngeal cancer prevention and treatment through elucidating the association between certain psychosocial factors and laryngeal cancer.

The question of whether psychological factors affect cancer development and progression has long been debated upon; this is not only of interest to scientists, but also of importance to patients. Although researchers have progressed considerably towards answering this question, no definitive conclusion has yet been reached. Garssen, upon summarizing ~30 years of research, identified stressful life events, social relationships, distress levels and the number of psychological problems, having a psychiatric diagnosis, repression, coping style, and personality factors, loss events, and locus of control, as potential factors (15). Some studies have further demonstrated that psychosocial factors are associated with the occurrence of cancer (16,17), while other studies considered them to be associated with cancer prognosis (18,19), and even recurrence and metastasis (20,21). To further advance our understanding of this association, we investigated the impact of life events and social support on the occurrence of laryngeal cancer and observed that the two groups exhibited significant differences in terms of scores on the life events and social support scales, and on all dimensions of the EPQ (P<0.05), except the psychoticism scale.

In the present study, the total and negative life event scores of the patient groups were found to be remarkably and significantly higher compared with those of the control group. Goodkin et al reported similar findings, in that the number of stressful life events was associated with cancer progression (22), albeit weakly. Another study investigating the impact of bereavement on cancer mortality classified cancer according to four types, namely lung, stomach, breast, and ‘other’. No effect of bereavement on cancer mortality was observed among women, while in men, bereavement predicted a higher cancer mortality rate. The higher mortality rate in bereaved men was observed for only those with lung and ‘other’ cancers. The bereavement effect on cancer was highest for the younger group of men (aged 35–64 years), and entirely absent for the oldest group (age 75–84 years) (23). Overall, the results for life events suggest that, compared with the healthy population, patients with laryngeal cancer experienced greater mental and psychological stress and more negative emotions prior to their illness. This allows us to tentatively infer that considerable psychological stress and negative emotions may be a risk factor for laryngeal cancer. Several studies have indicated that negative life events (such as poor marital quality, loneliness, depressed mood, dissatisfaction with social support, unemployment and bereavement) affect immune system functioning; specifically, they cause immune suppression. However, the association among stress, the immune system and disease has not been fully elucidated. Negative life events may be associated with a reduction of natural killer (NK) cytotoxicity.

Regarding social support, we found that patients with laryngeal cancer obtained significantly lower scores on objective support, subjective support, and support utilization scales compared with the control group. Shaffer et al similarly found that male medical students who developed cancer while being followed up over 16–32 years had lower scores on closeness to their fathers at initial assessment, as compared to the entire group or the healthy subgroup (24). Another study reported that women with few relationships, particularly friends, and those experiencing feelings of social isolation, were at higher risks of developing cancer and dying from cancer; notably, this was not found in men (25). Levy et al found that better perceived social support was associated with a longer disease-free interval within a subgroup of women who exhibited recurrence (26). An impressive study in this area was conducted by a Canadian study group, Maunsell et al, who found a type of dose-response relationship for social support and cancer survival rate; survival rates at 7 years increased stepwise in women reporting none, one, or at least two types of confidants (27). Our findings suggest that laryngeal cancer patients lacked social assistance and support, both subjectively and objectively, compared with healthy individuals. As a result, laryngeal cancer patients were more prone to psychological and mental isolation and helplessness, which suggests that reduced social support may be a predisposing factor for laryngeal cancer. Social support is considered to promote biological or behavioral adaptations under conditions of stress. This, in turn, may lead to positive effects on immune functioning and may limit the effects of stress-related endocrine changes that are possibly associated with tumor proliferation. This may result in better treatment compliance and the adoption of better health behaviors, which will generally exert positive effects on overall physical condition.

Regarding the EPQ dimensions, the extraversion scale scores of the patient and control groups were close to 15 and 8, respectively, and these differences were significant. This result confirms that, compared with healthy individuals, patients with laryngeal cancer appear to prefer excitement and are more prone to emotional impulsiveness. Similarly, the neuroticism scale scores of the patient and control groups were close to 14 and 9, respectively, which was also a significant difference. This suggests that, compared with healthy individuals, patients with laryngeal cancer are more prone to anxiety and emotional instability. Somewhat relatedly, one population-based prospective cohort study found a significant association between neuroticism and risk of death, particularly among women (28). Furthermore, a cross-sectional analysis from the Miyagi Cohort Study demonstrated that the personality traits of extraversion, neuroticism and psychoticism were significantly associated with attendance of gastric cancer screenings (29). van den Bergh et al reported that higher neurotic personality scores were associated with unfavorable effects for patients with early prostate cancer (30), while another study among cancer patients, non-cancer patients, and healthy individuals in a Japanese sample, indicated that the health-related quality of life score of individuals with tolerable/tolerant type personalities (high E, low N and high P scores) was higher compared with that of individuals with intolerable/intolerant type personalities (low E, high N and low P scores) and unclassified type personalities (31); notably, no differences in psychoticism scale scores were observed between the two groups. It was previously hypothesized that psychological stress may reduce NK cell activity (32). Psychological stress is also associated with the following two important processes for carcinogenesis: Poorer repair of damaged DNA and alterations in apoptosis, which play a role in malignant diseases. Conversely, the possibility that psychological interventions may enhance immune functioning and survival among cancer patients clearly merits further exploration, as does the evidence suggesting that social support may be a key psychological mediator.

The present study demonstrated that significant life and mental stress, proneness to anxiety and emotional instability are risk factors for laryngeal cancer, whereas sufficient social support and high utilization of social support are protective factors. Palermo et al systematically analyzed the effect of psychosocial factors on various stages of tumor development; they believed that psychosocial factors may increase susceptibility to cancer by altering the state of the body (e.g., increased possibility of genetic mutation, decreased DNA repairing capability and reduced immune function) (33). Hofsø et al (34)noted that mental status was closely associated with the functioning of the nervous, endocrine and immune systems. Additionally, mental disorders, such as depression, may alter the stress levels and immune function of the body through the neuroendocrine immunomodulation system, thereby affecting tumor occurrence and progression (34,35). In summary, several psycho-physiological mechanisms were found to be relevant. First, participants with high emotional constraint and/or high negative affectivity respond to stress with greater increases in heart rate, blood pressure and sweating, compared with low-anxiety, non-constrained individuals, and they also have higher basal cortisol levels. Second, decreased monocyte counts, elevated serum eosinophils and hyperglycemia have been found in low-anxiety/high-constraint individuals, when compared to their low-anxiety/low-constraint counterparts. This suggests that the elevation of another stress hormone, adrenocorticotropic hormone, the stimulant to cortisol secretion, and β-endorphin are both derived from a large precursor molecule, pro-opiomelanocortin, and both are released within min of exposure to mental stress. Therefore, mental stress is associated with physiological processes characteristic of emotionally constrained patients. Third, stress-induced immunosuppression is more pronounced with high emotional constraint and control over one's feelings rather than with low emotional constraint and lack of control. These physiological stress responses are known to exert deleterious health effects; however, the pathways through which they may adversely affect cancer progression remain under investigation. Furthermore, emotional distress and the psychological processes regulating it may also affect cancer progression indirectly through affecting health behavior.

The present study has several limitations. First, the interactions between the investigated factors were not considered. Second, due to different geographic populations having different dispositions, this study surveyed populations only from northern China. This may have resulted in some degree of bias in the results. Due to the abovementioned reasons and certain factors that have not been taken into consideration, it is difficult to establish with certainty whether the psychosocial factors in this study per se are risk factors for laryngeal cancer based on our study findings alone.

However, our results suggest that harmonic social relations and less dramatic mood swings may help reduce the risk of laryngeal cancer; otherwise, this risk increases. Therefore, positive social support should be provided to groups exhibiting depressed mood, in order to prevent the development of serious physical illnesses. Moreover, warning should be given to high-risk groups, including those with higher proneness to anxiety and emotional instability, to help in the prevention of adverse consequences. Such warnings could be paired with behavioral interventions to change insalubrious lifestyles and unhealthy living habits, which may make a positive contribution to the prevention and treatment of laryngeal cancer.