Investigating Factors Influencing Subjective Taste and Smell Alterations in Colorectal Cancer Patients

doi:10.21203/rs.3.rs-4699737/v1

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Investigating Factors Influencing Subjective Taste and Smell Alterations in Colorectal Cancer Patients

https://doi.org/10.21203/rs.3.rs-4699737/v1

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Purpose

This study aimed to assess the factors influencing self-reported taste and smell disturbances in patients with colorectal cancer.

Methods

A total of 152 participants were enrolled in the study. All subjects completed surveys that assessed taste and smell alterations using the Taste and Smell Survey (TSS), linear analog self-assessment (LASA), Patient-Generated Subjective Global Assessment (PG-SGA), and Pittsburgh Sleep Quality Index (PSQI). The TSS gathered data on the nature of taste and smell changes and their impact on quality of life. LASA was employed to evaluate the quality of life in cancer patients, while PG-SGA was used to indicate the nutritional status of the participants. PSQI was used to evaluate sleep quality.

Results

Among the 152 colorectal cancer patients, the total TSS score was 5.68 ± 2.84. No changes were observed in 5 cases (3.3%), mild changes in 58 cases (38.2%), and moderate to severe changes in 89 cases (58.6%). The severity of taste and smell disturbances increased with tumor stage, the cycle of chemotherapy, deteriorating sleep quality, and poor nutritional status, displaying significant correlations. Additionally, 83 patients (54.6%) complained of taste abnormalities, while 81 (53.3%) reported smell abnormalities.

Conclusion

Taste and smell disturbances are prominent in colorectal cancer patients. Taste abnormalities are significantly correlated with tumor stage, the cycle of chemotherapy, sleep quality, and nutritional status. Recognizing the high prevalence of taste and smell abnormalities and the influencing factors among patients with colorectal cancer may aid in predicting and understanding the severity of these symptoms more effectively.

colorectal cancer

chemotherapy

Taste and smell disturbances

quality of life

quality of sleep

Taste and smell are essential chemical senses for perceiving food flavors like sweet, sour, bitter, and salty and identifying environmental odors. Both senses are crucial for survival and reproduction. Disruptions of these sensations, called sensory dysfunctions[9], include anosmia, dysosmia, parosmia, hyposmia, phantosmia, and agnosia for smell and total loss of taste, taste distortion, or perception of taste without stimuli for taste[16]. These changes often manifest as symptoms of chronic illnesses affecting endocrine, metabolic, and neurological systems[15]. The exact mechanisms behind taste and smell abnormalities remain uncertain due to their complex origins and the diverse cancer populations being studied.

Colon cancer, originating in the inner lining of the large intestine, typically affecting the colon or rectum, is increasing rapidly in China[31]. Unlike other cancers, it often remains asymptomatic in the early stages, leading to delayed diagnosis and treatment[29]. Symptoms such as altered bowel habits, abdominal discomfort, and weight loss can significantly disrupt daily activities and quality of life[30]. The intricate correlation between colorectal cancer and changes in taste and smell perception is often overlooked. Chemotherapy, the primary treatment for colon cancer, affects not only cancer cells but also mucosal, olfactory, and gustatory receptors, impacting these senses[1]. Outside of the well-documented impact of chemotherapy, it is yet to be definitively established whether additional factors contribute to the alterations in gustatory and olfactory perception observed in patients diagnosed with colon cancer. This necessitates further research to understand multitude of factors on taste and smell perception and explore mitigation strategies for better patient outcomes.

This study investigates the relationship between colorectal cancer and alterations in taste and smell perceptions, identifying key influencing factors. The findings provide a novel perspective on the impact of colorectal cancer on daily life and offer a scientific basis for developing effective intervention strategies. Multi-targeted interventions aim to mitigate the adverse effects of taste and smell changes in colorectal cancer patients, enhancing comfort and overall quality of life.

Patients

Patients (both outpatients and inpatients) with histologically confirmed, unresectable adenocarcinoma of the colon or rectum, who had undergone a maximum of two prior chemotherapy regimens, were enrolled in this study conducted at the Oncology Department of Xi-Jing Hospital, a leading tertiary-care facility in China. A total of 152 patients with colorectal cancer were surveyed from January 2023 to August 2023. Informed consent was obtained from all participants. The protocol and study design were approved by the hospital's ethics committee under IRB number KY20232235-3, conducted in accordance with the Declaration of Helsinki. The exclusion criteria were: (i) chronic conditions linked to neuropathy or gastrointestinal disorders, (ii) cognitive impairment, (iii) indeterminate lesion extent and unclear treatment efficacy, and (iv) incomplete clinical data.

Demographics Questionnaire

Demographic and clinical data were collected through specific inquiries during the baseline assessment. This data included gender, age, self-reported height and weight, smoking and alcohol consumption habits, and the presence of comorbidities. Obesity was defined as a body mass index (BMI) of 30 or higher. Participants also provided information on their current medications, recent tests, past medical conditions, and surgical history.

Taste and Smell Survey

The Taste and Smell Survey (TSS) was used to assess taste and smell perception changes among cancer patients[17, 23]. The questionnaire comprised nine items related to taste changes and five addressing olfactory alterations. A patient was considered to have experienced taste and smell changes if they met either of the following criteria: i) answering "yes" to at least 4 out of the items inquiring about the presence of any taste or smell change; ii) reporting alterations in sensitivity to sweet, salty, bitter, sour tastes, or smell. Taste distress and olfactory abnormalities were rated on a 3-point scale: 0 indicating barely noticeable, 1 suggesting mild to moderate, and 2 denoting severe impact. The remaining questions were assessed on a 2-point scale: 0 for no change and 1 for the presence of change, with a total possible score of 16. Based on the total score, the degree of alteration was categorized into four levels: 0–1 points indicated no change, 2–4 points signified mild changes, 5–9 points represented moderate changes, and 10–16 points implied severe changes. The internal consistency reliability was 0.89, as reported in a previous study[4].

Measurement of Quality of Life

Quality of life among cancer patients was assessed using the LASA tool, a validated instrument for comprehensive evaluation of overall quality of life[21]. The LASA is recognized as a reliable brief tool for quality of life appraisal in cancer patients[14], with significant correlations with established multi-item scales. This tool employs an 11-point Likert scale, where 0 represents "couldn't be worse" and 10 signifies "couldn't be better," with higher scores indicating a better quality of life.

Assessment of Nutritional Status.

The Patient-Generated Subjective Global Assessment (PG-SGA) scoring system comprehensively assesses nutritional status by evaluating weight loss, food intake, symptoms, activity and function, disease status, metabolic requirements, and physical examination. The scoring results categorize a patient's nutritional status into four levels: well nourished (0–1 point), mild malnutrition (2–3 points), moderate malnutrition (4–8 points), and severe malnutrition (≥ 9 points)[12]. This system provides healthcare professionals with accurate nutritional assessments to guide appropriate intervention strategies.

Measurement of sleep quality.

The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality[8]. The PSQI includes 19 self-reported items and five additional items, with only the 18 primary items contributing to the total score. These items are categorized into seven components, each scored from 0 to 3. The total PSQI score ranges from 0 to 21, with higher scores indicating poorer sleep quality. A score above seven suggests a sleep disorder. The PSQI has demonstrated strong internal consistency and reliability, with Cronbach's α coefficients ranging from 0.82 to 0.83[27].

Statistical Analysis.

Data analysis was performed using SPSS 21.0 software (SPSS Inc., Chicago, IL, USA). Normally distributed data were presented as mean ± standard error of the mean (SEM), while non-normally distributed data were expressed as median and range. Continuous variables were compared using the t-test, and the chi-square test was used to assess relationships between qualitative variables. One-way ANOVA was employed to compare quantitative variables. A P-value of less than 0.05 was considered statistically significant. Violin plots and correlation analysis were generated using R software in R studio (version 4.3.1), and data processing was conducted with Microsoft Excel (Microsoft Corporation, Redmond, WA, USA).

Characteristics of the study population.

A total of 152 adult patients undergoing chemotherapy for various malignancies were recruited and completed initial evaluations. Participant demographics are presented in Table 1. The median age of the study cohort was 44 years, with a predominant female representation of 79 out of 152 participants (52.0%). Comorbidities were documented in 43 cases (28.3%), while 48 patients (31.6%) were classified as having tumor stage III. Additionally, 17 patients (11.2%) underwent more than 5 cycles of chemotherapy.

Alterations in the taste and smell perceptions in patients with different demographic characteristics.

Among the 152 colorectal cancer patients, the total TSS score was 5.68 ± 2.84 (Table 2). No change was observed in 5 cases (3.3%), mild changes in 58 cases (38.2%), and moderate to severe changes in 89 cases (58.6%). There were no significant differences in taste and smell alterations among patients of different sexes, ages, drinking habits, smoking habits, comorbidities, tumor stages, or households (P > 0.05). However, significant differences in TSS scores were observed among patients with different cycles of chemotherapy, quality of life, nutritional status, and sleep quality (P < 0.05) (Fig. 1A-E). Further analysis revealed that the severity of taste and smell disturbances increased with tumor stage, the number of chemotherapy cycles, deteriorating sleep quality, and poor nutritional status, showing a significant correlation(Fig. 1A-E, Fig. 2C-D). However, no significant correlation was observed between TSS scores and quality of life (P > 0.05)(Fig. 2A).

Taste Survey of the TSS.

In the taste survey, 83 patients (54.6%) reported changes in their taste perception. Notably, 40 patients (55.6%) experienced a weakening of the sweet taste, and 27 patients (51.9%) experienced a weakening of the salty taste, significantly higher than those experiencing a strengthening of these tastes. In contrast, a higher proportion of patients reported a stronger taste of bitterness and sourness. Additionally, 21 patients (13.8%) reported severe to intolerable changes in their sense of taste, while 62 patients (40.8%) experienced mild to moderate changes (Table 3).

Smell Survey of the TSS.

In the smell survey, 81 patients (53.3%) reported alterations in their sense of smell compared to their pre-treatment state, while 63 patients (41.4%) observed changes in the aroma of their food. A common observation was a perceived reduction in olfactory acuity. Specifically, 62 patients (40.8%) experienced mild to moderate changes in their sense of smell, whereas 19 patients (12.5%) reported severe to intolerable changes (Table 4).

The chemical senses of taste and smell are vital for survival, alerting individuals to potential hazards and aiding in maintaining proper nutrition. Physiological alterations in these senses can signal dangers, such as gas leaks, and prevent the ingestion of harmful substances[7]. In contrast, pathological changes can increase the risk of malnutrition (both under and over-nutrition)[13], contribute to low mood, limit social interactions, and reduce overall quality of life[28]. This study highlights that taste and smell irregularities are common among colorectal cancer patients, with a positive correlation to tumor stage, chemotherapy cycles, sleep quality and nutritional status. Additionally, a significant number of patients reported weakened responses to salty and sweet tastes, with heightened sensitivity to sour and bitter flavors, consistent with previous research[23]. The exact mechanisms behind taste and smell changes in colorectal cancer remain unclear. While traditionally attributed to chemotherapy-induced neurological disorders[24], recent research suggests a link to abnormal brain-gut axis interactions[2, 11]. This axis facilitates bidirectional communication between the gastrointestinal tract and the brain through various cellular and molecular pathways[3]. Studies indicate that enterochromaffin cells may act as sensors for odorants and taste molecules[18]. Additionally, alterations in the insular lobe, a brain structure crucial for taste and smell processing, have been observed in colorectal cancer patients[6, 20]. These findings suggest gastrointestinal conditions may influence taste and olfactory perceptions through complex interactions involving genetic variants, epigenetic factors, and gut microbiota.

This study is the first to investigate the prevalence of self-reported chemosensory dysfunction in colorectal cancer patients. Comprehensive assessments are essential to determine the true prevalence of these dysfunctions, as factors influencing taste and smell changes are multifaceted and not solely due to chemotherapy[10]. The findings indicate that many colorectal cancer patients experience alterations in taste and smell perceptions associated with chemotherapy cycles, poor sleep quality, and compromised nutritional status. Furthermore, there is a positive correlation between tumor stage and changes in taste and smell perceptions, supporting the study's conclusions.

Definitive biomedical solutions for alleviating or restoring taste and smell functions and addressing changes in taste and smell perceptions are currently lacking[22]. Research has highlighted how patients develop strategies to circumvent unpleasant taste or smell experiences and mitigate the social repercussions of such changes[25]. Patients with a proactive stance tend to manage their dietary habits by opting for healthier food choices (reducing fat intake, increasing vegetable consumption), selecting seasonings to modify food taste, and avoiding odors[5]. Therefore, colorectal cancer patients must acknowledge potential alterations in their taste and smell faculties and the influencing factors to regulate their dietary patterns effectively. Healthcare providers should also consider this aspect, as this research suggests it could enhance the prediction and comprehension of lower gastrointestinal symptoms' severity.

This study has several limitations. Firstly, using self-reported food-related smell and taste scores rather than objective tests[19, 26] introduces inherent recall bias, potentially leading participants to understate or exaggerate their sensory experiences unconsciously. Secondly, the study's small sample size necessitates larger-scale, multicenter investigations in the future. The challenge of assisting patients with taste and smell alterations underscores the importance of developing diagnostic tools, evaluation methods for such changes, and evidence-based treatment strategies. Furthermore, the relationship between food-related smell and taste scores, lower gastrointestinal symptoms, and psychological comorbidities remains unclear and requires further clinical investigation.

Taste and smell abnormalities are common among colorectal cancer patients but are often overlooked in the diagnosis of gastrointestinal diseases. This study reveals that taste and smell disturbances are prevalent in colorectal cancer patients, influenced not only by chemotherapy but also by the patient's brain-gut axis, sleep quality, and nutritional status. These findings underscore the complexity of chemosensory disruptions in cancer patients. Therefore, it is crucial to recognize the high prevalence of taste and smell abnormalities in colorectal cancer patients and their significance in assessing the severity of lower gastrointestinal symptoms. In addition, future research should explore ways to manage taste and smell changes in colorectal cancer patients. In the meantime, current findings can be used to improve patient-centered care.

Competing interests:
The authors declare no competing interests.

Funding

This study is supported by the Innovative Medical Research Advancement Initiative of Xijing Hospital (XJZT24CY17).

Author Contribution

WW: conceptualization, methodology, investigation, formal analysis, writing—original draft preparation, writing—review and editing; ZL, XZ, YL, SK: conceptualization, methodology, writing—review and editing, supervision; JS, HZ: conceptualization, methodology, writing—review and editing, supervision, project administration, funding acquisition.All authors reviewed the manuscript.

Data availability

The data supporting this study's findings are not openly available due to sensitivity reasons and are available from the corresponding author upon reasonable request.

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Table 1. Demographic and clinical characteristics of patients

Variable		Patient (n = 152)
Sex	Male	79
Sex	Female	73
Age(years)	<30	13
	31–40	34
	41–50	67
	≥51	38
BMI (kg m-2)	< 25	59
	25–29.9	55
	≥ 30	38
Drinking habits	Ever	39
Drinking habits	Never	113
Smoking habits	Ever	6
Smoking habits	Never	146
Comorbidity	Any	43
Comorbidity	None	109
Tumor stage	Ⅰ	28
	Ⅱ	76
	Ⅲ	48
Cycle of chemotherapy	1-2	111
	3-4	24
	≥5	17
Household	Alone	27
Household	Other	125

Table 2. Colorectal cancer patients' TSS score across demographics.

Characteristics		Patient (n=152)	TSS score (x±s)	t/F	P value
Sex	Male	79	5.43±2.83	t=-1.119	0.265
Sex	Female	73	5.95±2.84	t=-1.119	0.265
Age(years)	<30	34	5.97±2.77	F=2.328	0.077
	31–40	67	4.91±2.57
	41–50	38	6.60±3.33
	≥51	39	5.59±2.65
Drinking habits	Ever	39	5.05±2.72	t=-1.608	0.110
Drinking habits	Never	113	5.89±2.85	t=-1.608	0.110
Smoking habits	Ever	6	7.00±3.95	t=-1.166	0.245
Smoking habits	Never	146	5.62±2.79	t=-1.166	0.245
Comorbidity	Any	43	6.33±3.35	t=-1.592	0.116
Comorbidity	None	109	5.42±2.58	t=-1.592	0.116
Tumor stage	Ⅰ	57	4.56±2.43	F=12.208	0.000
	Ⅱ	68	5.94±2.88
	Ⅲ	27	7.63±2.79
Cycle of chemotherapy	1-2	111	5.04±2.34	F=17.117	0.000
	3-4	24	6.42±2.99
	≥5	17	8.82±3.36
LASA	0-3	28	6.14±2.72	F=3.310	0.039
	4-6	53	6.26±2.83
	7-10	71	5.06±2.80
PG-SGA	0-1	27	3.70±2.32	F=11.079	0.000
	2-3	42	5.31±2.24
	4-8	62	6.03±2.62
	≥9	21	7.90±3.39
PSQI	1-6	126	5.08±2.29	t=-4.959	0.000
PSQI	≥7	26	8.58±3.44	t=-4.959	0.000
Household	Alone	27	5.89±2.83	t=0.426	0.671
Household	Other	125	5.63±2.85	t=0.426	0.671

Table 3. Breakdown of the detailed taste complaints from the taste and smell survey.

		Patient (n = 152)	(%)
	Foods taste different than they used to	47	30.9
	I have noticed a change in my sense of taste	83	54.6
	I have a persistent bad taste in my mouth	38	25.0
	Chemotherapy interferes with my sense of taste	62	40.8
	I have noticed a change in the sweet	72	47.4
	Sweet tastes stronger	32	44.4
	Sweet tastes weaker	40	55.6
	I have noticed a change in the salt	52	34.2
	Salt tastes stronger	25	48.1
	Salt tastes weaker	27	51.9
I have noticed a change in the sour		36	23.7
Sour tastes stronger		25	69.4
Sour tastes weaker		11	30.6
	I have noticed a change in the bitter	33	21.7
	Bitter tastes stronger	20	60.6
	Bitter tastes weaker	13	39.4
	Rate abnormal sense of taste
	Insignificant	69	45.4
	Mild to moderate	62	40.8
	Severe to intolerable	21	13.8

Table 4. Breakdown of the detailed smell complaints from the taste and smell survey.

	Patient (n=152)	(%)
I have noticed a change in my sense of smell	81	53.3
Chemotherapy interferes with my sense of smell	67	44.1
Foods smell different than they used to	63	41.4
I have noticed a change in odors	55	36.2
Stronger	16	29.1
Weaker	39	70.9
Rate abnormal sense of smell
Insignificant	71	46.7
Mild to moderate	62	40.8
Severe to intolerable	19	12.5

No competing interests reported.

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You are reading this latest preprint version

Investigating Factors Influencing Subjective Taste and Smell Alterations in Colorectal Cancer Patients

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Materials and methods

Patients

Demographics Questionnaire

Taste and Smell Survey

Measurement of Quality of Life

Statistical Analysis.

Results

Discussion

Conclusions

Declarations

Competing interests:
The authors declare no competing interests.

Funding

Author Contribution

Data availability

References

Tables

Additional Declarations

Status:

Version 1

Investigating Factors Influencing Subjective Taste and Smell Alterations in Colorectal Cancer Patients

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Materials and methods

Patients

Demographics Questionnaire

Taste and Smell Survey

Measurement of Quality of Life

Statistical Analysis.

Results

Discussion

Conclusions

Declarations

Competing interests: The authors declare no competing interests.

Funding

Author Contribution

Data availability

References

Tables

Additional Declarations

Status:

Version 1

Competing interests:
The authors declare no competing interests.