
==== Front
Indian J Dermatol
Indian J Dermatol
IJD
Indian J Dermatol
Indian Journal of Dermatology
0019-5154
1998-3611
Wolters Kluwer - Medknow India

IJD-69-317
10.4103/ijd.ijd_1095_23
Original Article
Interaction Effect of Psoriasis and Cancer on the Risk of All-Cause Mortality: A Prospective Cohort Study of NHANES Data
Si Zixiang
Zhao Honglei 1
Ying Jieya
From the Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou, Zhejiang, China
1 Department of Dermatology, Beilun People’s Hospital, Ningbo, Zhejiang, China
Address for correspondence: Dr. Jieya Ying, Department of Dermatology, Hangzhou Third People’s Hospital, 38th Westlake Avenue, Hangzhou, 310000, China. E-mail: 17826866070@163.com
Jul-Aug 2024
19 8 2024
69 4 317327
11 2023
4 2024
Copyright: © 2024 Indian Journal of Dermatology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Background:

The relationship between psoriasis, cancer, and mortality has been reported in observational studies. Considering the high heterogeneity in systematic review and meta-analysis and inconsistent results in previous studies, the association between psoriasis, cancer, and mortality warrants more investigation. The primary objective of this study was to explore the joint impact of psoriasis and cancer on mortality in a representative cohort of adults residing in the United States.

Methods:

We analysed comprehensive data obtained from the National Health and Nutrition Examination Study conducted during the periods of 2003–2006 and 2009–2014. Multivariable logistic regression analyses were performed to assess the relationship between psoriasis and cancer. The vital status of participants was tracked until 31 December 2019. A four-level variable combining information on psoriasis and cancer was created, and survival probability was evaluated using the Kaplan–Meier curve and Cox regression analysis. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to analyse the association between psoriasis/cancer and all-cause mortality.

Results:

In total, this study included 15,234 participants, among whom 418 had psoriasis and 1213 had cancer. The findings from the logistic regression analyses indicated a heightened risk of cancer among individuals with psoriasis in comparison to those without psoriasis. Moreover, the risk of skin cancer was higher in participants with psoriasis compared to those without psoriasis. Compared with individuals without cancer and psoriasis, the all-cause mortality HRs were 1.25 (95% CI: 0.87–1.78) for individuals with psoriasis only, 1.48 (95% CI: 1.20–1.82) for participants with cancer only, and 2.28 (95% CI: 1.12–4.63) for individuals with both psoriasis and cancer.

Conclusion:

The results of our study demonstrated a noteworthy and positive correlation between psoriasis, cancer, and all-cause mortality. These findings indicate that individuals who have both psoriasis and cancer face an increased likelihood of mortality.

KEY WORDS:

Cancer
mortality
NHANES
psoriasis
risk
==== Body
pmcIntroduction

There are approximately 33 million cancer survivors worldwide.[1] The number of cancer survivors continues to increase in the United States due to the growth and aging of the population as well as advances in early detection and treatment.[2] Cancer remains the most common cause of disease-related death and carries a significant burden. Cancer survival is defined as the time between cancer diagnosis and mortality. Now, people with cancer might have a longer life expectancy due to various surgical methods and innovative therapeutic drugs. As survival rates rise, survivors are more likely to experience long-term health issues; up to 70% report having at least one chronic health issue, and up to 40% have serious issues that necessitate continuous medical monitoring or treatment.[34]

Psoriasis, known as chronic plaque or psoriasis vulgaris, is a persistent inflammatory skin disorder that impacts a considerable portion of the adult population in the United States, affecting around 3.0% or over 7.5 million adults. This condition imposes a significant socioeconomic burden on individuals and society as a whole.[56] Recent evidence indicates that psoriasis is not solely limited to skin manifestations but rather a systemic inflammatory disease. Psoriasis is associated with various coexisting or co-occurring comorbidities.[7] Concerns have been raised whether psoriasis itself, psoriasis-associated risk factors, or treatment of psoriasis might lead to an increased risk of cancer.[8]

Considering the substantial prevalence of psoriasis and cancer in the population, it is crucial to explore the combined impact of psoriasis and cancer on the risk of mortality. This study utilised data from two phases of the National Health and Nutrition Examination Survey (NHANES), 2003–2006 and 2009–2016, to investigate the relationship between psoriasis, cancer, and all-cause mortality. The primary hypothesis of this study was that individuals with either psoriasis or cancer would have a higher mortality rate compared to those without either condition, with the highest risk observed among individuals with both psoriasis and cancer. Our findings could provide information on strategies to reduce mortality in individuals with psoriasis and cancer.

Materials and Methods

Study design and population

The NHANES program serves as a valuable cross-sectional tool for assessing the overall health and nutritional status of the American population. It utilises a combination of interviews and physical examinations to collect comprehensive data on demographics, dietary habits, questionnaire responses, medical examinations, and laboratory results. The NHANES protocol has received approval from the ethics review board of the National Centre for Health Statistics. Written informed consent is obtained from all participants in the program, ensuring their voluntary involvement and protection of their rights.

In the present study, we utilised comprehensive data from five continuous NHANES cycles, specifically from the years 2003–2004, 2005–2006, 2009–2010, 2011–2012, and 2013–2014. The study cohort comprised adult individuals who underwent a two-step process involving an initial interview conducted at their residence to gather sociodemographic information and medical history, followed by a comprehensive evaluation at a mobile examination center. To ensure the quality and integrity of the analysis, we only included adult participants who had complete data on both psoriasis and cancer. Consequently, individuals with missing information on covariates were excluded from the analytical population.

Diagnostic of psoriasis and cancer

To ascertain the presence of psoriasis among participants, data collection relied on self-administered questionnaires during the 2003–2006 and 2009–2014 NHANES surveys. In order to identify individuals with psoriasis, a positive response to the question, “Have you ever been told by a health care provider that you had psoriasis?” was considered indicative of the condition.

Self-reported cancer diagnoses were obtained from the medical condition questionnaire administered to all participants 20 years and older. Participants were first asked “Have you ever been told by a doctor or other health professional that you had cancer or a malignancy of any kind?” Those who responded yes were then asked to indicate which type of cancer it was, and they were able to indicate up to three different cancer types.[9] We extracted data for five cancer types: skin, prostate, breast, cervix (cervical), and colon.

Covariates

Control variables that may act as confounding factors in this study included socioeconomic and health-related factors. Socioeconomic characteristics included sex, race, age, education level, and marital status. Education level was divided into four categories: less than high school, high school or equivalent, some college or AA degree, and college graduate or above. Health-related characteristics encompassed body mass index (BMI), smoking status, and drinking status. Smoking status was divided into three categories: never smokers (smoked less than 100 cigarettes in life), former smokers (smoked more than 100 cigarettes in life and smoke not at all now), and now smokers (smoked more than 100 cigarettes in life and smoke some days or every day). Individuals with systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg were classified as having hypertension. Additionally, a self-reported diagnosis of hypertension by a physician and the use of antihypertensive medication were also considered as indicators of the condition. The presence of diabetes was defined by a diagnosis of diabetes, currently taking glucose-lowering medication, or having HbA1c ≥6.5%, fasting serum glucose level ≥7.0 mmol/L, or random blood glucose ≥11.1 mmol/L.

Ascertainment of mortality

The NCHS database provides NHANES public-use-linked mortality information until 31 December 2019. These files were linked to the National Death Index to establish the survival status of participants. To confirm survival status, a total of 12 characteristics were obtained to connect the NHANES samples with the National Death Index. For surviving participants, the survival time (in months) was calculated from the date of the initial interview to either the date of death or the conclusion of the follow-up period (31 December 2019). The primary focus of our analysis was to examine all-cause mortality as the outcome variable.

Statistical analysis

To account for the complex, multistage, stratified, cluster sampling design employed in NHANES, appropriate weighting procedures were implemented during the data analysis phase to derive nationally representative estimates.[10] All analyses considered the intricate sample design, utilising mobile examination centre sample weights to calculate estimates. Baseline demographic and clinical characteristics were summarised and stratified by psoriasis and cancer status. Continuous variables were reported as survey-weighted means with 95% confidence intervals (CIs), while dichotomous variables were presented as survey-weighted percentages with 95% CI. Weighted t-tests or Chi-square tests were employed to compare continuous or categorical variables across different groups, respectively.

We employed a multivariate logistic regression model to calculate odds ratios (ORs) and their corresponding 95% CIs to investigate the association between psoriasis and cancer, while adjusting for social demographic covariates. The Kaplan–Meier method was utilised to assess survival rates across different groups. Univariate and multivariate Cox proportional-hazards regression models were then utilised to calculate hazard ratios (HRs) and their corresponding 95% CIs to analyse the association between psoriasis and all-cause mortality, taking cancer status into account. To evaluate the combined effects, participants were categorised based on psoriasis (yes or no), cancer (yes or no), and the HRs of mortality were compared among the groups: neither psoriasis nor cancer, only psoriasis, only cancer, and both psoriasis and cancer. Model 1 represented the unadjusted crude model. Model 2 adjusted for sex, race, age, BMI category, education level, and marital status, and model 3 additionally accounted for smoking status, drinking status, hypertension, and diabetes.

The statistical analyses were conducted using R software (version 4.3.1). Statistical significance was considered at a two-sided P-value < 0.05.

Results

In Figure 1, the inclusion and exclusion criteria for this study are presented. A comprehensive total of 15,234 participants were included in the study. Table 1 provides an overview of the demographic and clinical characteristics of the participants, both in the overall context and categorised by psoriasis and cancer status. Psoriasis was present in 2.744% of the study population, and cancer was present in 7.962% of the study population. Of note, cancer was diagnosed in 1213 individuals, of whom 61 had a history of psoriasis. The average age was 44 years, with 50.02% of participants being male and 69.22% being non-Hispanic white. Among individuals without cancer, psoriasis sufferers were more likely to be older, non-Hispanic white, have higher BMIs, have a history of smoking, and have hypertension. However, no significant difference was found between those with and without psoriasis among individuals with cancer.

Figure 1 The inclusion and exclusion criteria for this study

Table 1 Baseline characteristics of study population by presence of cancer and psoriasis

Variable	Overall (n=15,234)	Cancer	P	No cancer	P	
		
No Psoriasis (n=1,152)	Psoriasis (n=61)	No Psoriasis (n=13,664)	Psoriasis (n=357)	
Age (years)	44.24 (43.74, 44.73)	59.01 (57.86, 60.15)	57.65 (54.10, 61.21)	0.48	42.83 (42.39, 43.26)	45.64 (44.05, 47.22)	0.001	
Sex				0.27			0.3	
 Female	49.98 (47.00, 52.96)	60.39 (57.47, 63.32)	51.88 (36.80, 66.95)		48.99 (48.24, 49.73)	52.19 (46.23, 58.15)		
 Male	50.02 (46.93, 53.11)	39.61 (36.68, 42.53)	48.12 (33.05, 63.20)		51.01 (50.27, 51.76)	47.81 (41.85, 53.77)		
Race				0.83			<0.0001	
 Hispanic	4.69 (3.71, 5.67)	1.74 (0.86, 2.61)	2.06 (-0.38, 4.50)		5.00 (3.91, 6.10)	3.28 (1.72, 4.83)		
 Non-Hispanic White	69.22 (62.29, 76.14)	87.58 (85.12, 90.03)	90.33 (83.16, 97.51)		67.13 (63.86, 70.40)	81.28 (76.75, 85.80)		
 Non-Hispanic Black	11.16 (9.93, 12.38)	5.24 (3.84, 6.63)	3.48 (0.06, 6.90)		11.87 (10.31, 13.43)	6.09 (3.92, 8.27)		
 Mexican American	8.71 (7.14, 10.29)	2.52 (1.53, 3.51)	1.29 (-0.35, 2.93)		9.44 (7.51, 11.37)	3.87 (1.64, 6.10)		
 Other	6.23 (5.50, 6.95)	2.93 (1.63, 4.23)	2.84 (-2.63, 8.31)		6.56 (5.75, 7.36)	5.49 (2.96, 8.01)		
Education				0.17			0.48	
 Less than high school	15.59 (14.28, 16.91)	11.30 (8.90, 13.69)	12.37 (5.47, 19.28)		16.06 (14.70, 17.42)	13.27 (9.03, 17.51)		
 High school or equivalent	23.46 (21.35, 25.58)	21.49 (18.64, 24.34)	13.82 (4.67, 22.97)		23.69 (22.48, 24.91)	23.26 (19.01, 27.52)		
 Some college or AA degree	32.88 (30.76, 35.01)	33.74 (30.33, 37.15)	48.97 (31.23, 66.72)		32.74 (31.55, 33.94)	32.42 (26.29, 38.55)		
 College graduate or above	28.06 (25.36, 30.75)	33.47 (29.30, 37.64)	24.83 (10.64, 39.01)		27.50 (25.55, 29.46)	31.04 (24.79, 37.30)		
Marital status				0.47			0.49	
 Married	56.62 (52.19, 61.04)	64.88 (60.89, 68.87)	59.94 (46.75, 73.12)		55.77 (54.17, 57.36)	60.06 (55.11, 65.00)		
 Never married	18.82 (17.76, 19.89)	6.58 (5.08, 8.07)	3.02 (-1.70, 7.74)		20.01 (18.64, 21.38)	18.05 (13.80, 22.29)		
 Living with partner	7.88 (7.09, 8.68)	3.80 (2.51, 5.09)	6.66 (-1.56, 14.88)		8.28 (7.59, 8.96)	7.09 (4.34, 9.83)		
 Other	16.67 (15.44, 17.91)	24.75 (21.14, 28.35)	30.38 (18.80, 41.96)		15.95 (15.14, 16.76)	14.81 (10.79, 18.82)		
BMI category				0.48			0.003	
 <25	31.66 (29.46, 33.86)	31.14 (28.17, 34.11)	21.97 (8.09, 35.86)		32.03 (30.68, 33.38)	22.26 (17.61, 26.91)		
 25-30	32.65 (30.46, 34.83)	32.07 (28.22, 35.93)	32.97 (17.96, 47.98)		32.60 (31.47, 33.74)	35.81 (29.99, 41.64)		
 >=30	35.70 (33.17, 38.22)	36.78 (33.45, 40.12)	45.06 (28.90, 61.22)		35.37 (34.02, 36.72)	41.93 (36.61, 47.25)		
Smoking status				0.46			<0.0001	
 Never	54.08 (50.86, 57.30)	44.95 (40.84, 49.05)	36.52 (21.82, 51.22)		55.32 (53.86, 56.78)	42.66 (36.23, 49.10)		
 Former	22.54 (20.47, 24.61)	36.06 (32.09, 40.02)	39.04 (26.93, 51.15)		20.96 (19.78, 22.13)	32.78 (27.08, 38.48)		
 Now	23.38 (21.58, 25.17)	18.99 (16.29, 21.70)	24.44 (12.00, 36.88)		23.73 (22.44, 25.01)	24.56 (19.17, 29.95)		
Drinking status				0.54			0.55	
 Never	10.39 (8.89, 11.88)	8.95 (6.40, 11.50)	5.07 (-0.09, 10.23)		10.58 (9.23, 11.93)	9.16 (5.90, 12.43)		
 Former	14.53 (12.92, 16.14)	21.80 (18.77, 24.84)	20.38 (9.10, 31.67)		13.83 (12.74, 14.92)	15.40 (10.56, 20.23)		
 Now	75.08 (70.44, 79.72)	69.25 (64.84, 73.65)	74.55 (62.63, 86.46)		75.59 (73.62, 77.56)	75.44 (70.00, 80.88)		
Hypertension				0.64			0.01	
 No	66.08 (62.08, 70.09)	43.96 (40.81, 47.10)	40.56 (26.84, 54.28)		68.37 (67.05, 69.70)	59.06 (52.25, 65.87)		
 Yes	33.92 (31.38, 36.46)	56.04 (52.90, 59.19)	59.44 (45.72, 73.16)		31.63 (30.30, 32.95)	40.94 (34.13, 47.75)		
DM				0.36			0.81	
 No	82.61 (77.45, 87.77)	72.77 (69.93, 75.62)	70.37 (61.32, 79.42)		83.52 (82.77, 84.28)	83.17 (78.10, 88.25)		
 IGT	3.09 (2.74, 3.44)	4.35 (2.92, 5.78)	1.21 (-1.23, 3.65)		2.99 (2.70, 3.28)	3.08 (1.10, 5.07)		
 IFG	3.02 (2.65, 3.38)	3.81 (2.50, 5.11)	3.60 (-0.69, 7.88)		2.92 (2.50, 3.34)	3.89 (1.09, 6.70)		
 DM	11.28 (10.47, 12.09)	19.07 (16.66, 21.48)	24.82 (16.20, 33.44)		10.57 (9.96, 11.18)	9.85 (6.41, 13.28)		
BMI, body mass index; DM, diabetes mellitus; IFG, impaired fasting glycaemia; IGT, impaired glucose tolerance

As shown in Table 2, the logistic regression analyses demonstrated a positive relationship between psoriasis and the incidence of cancer. In model 1 (OR = 1.85; 95% CI: 1.30–2.63), model 2 (OR = 1.62; 95% CI: 1.10–2.39), and model 3 (OR = 1.52; 95% CI: 1.02–2.25), the risk of cancer was higher in participants with psoriasis compared to those without psoriasis. A multivariate regression analysis revealed that sex, age, race, education level, smoking status, marital status, and drinking status were significantly related to cancer. Hypertension (OR = 1.41; 95% CI: 1.22–1.63) was also significantly associated with an increased risk of cancer.

Table 2 Relationship between psoriasis and cancer among adults aged 20 years or older

Variable	Model 1	Model 2	Model3	
			
OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P	
Psoriasis							
 No	ref	ref	ref	ref	ref	ref	
 Yes	1.85 (1.30,2.63)	<0.001	1.62 (1.10, 2.39)	0.02	1.52 (1.02, 2.25)	0.04	
Sex							
 Female			ref	ref	ref	ref	
 Male			0.69 (0.60, 0.79)	<0.0001	0.64 (0.55, 0.74)	<0.0001	
Age group							
 ≤49			ref	ref	ref	ref	
 50-65			3.37 (2.65, 4.28)	<0.0001	3.01 (2.34, 3.87)	<0.0001	
 ≥65			10.25 (8.37,12.56)	<0.0001	8.63 (6.83,10.90)	<0.0001	
Race							
 Hispanic			ref	ref	ref	ref	
 Non-Hispanic White			2.56 (1.66, 3.93)	<0.0001	2.38 (1.54, 3.66)	<0.001	
 Non-Hispanic Black			1.11 (0.70, 1.78)	0.64	1.02 (0.63, 1.64)	0.95	
 Mexican American			0.89 (0.54, 1.46)	0.63	0.91 (0.55, 1.52)	0.71	
 Other			1.09 (0.56, 2.13)	0.8	1.03 (0.52, 2.05)	0.92	
Education							
 Less than high school			ref	ref	ref	ref	
 High school or equivalent			1.13 (0.84, 1.51)	0.41	1.18 (0.90, 1.57)	0.23	
 Some college or AA degree			1.42 (1.08, 1.86)	0.01	1.54 (1.19, 2.00)	0.002	
 College graduate or above			1.48 (1.11, 1.98)	0.01	1.78 (1.33, 2.38)	<0.001	
Marital status							
 Married			ref	ref	ref	ref	
 Never married			0.58 (0.44, 0.76)	<0.001	0.59 (0.44, 0.78)	<0.001	
 Living with partner			0.85 (0.57, 1.26)	0.41	0.78 (0.52, 1.18)	0.24	
 Other			1.01 (0.83, 1.22)	0.96	0.96 (0.79, 1.17)	0.67	
BMI category							
 <25			ref	ref	ref	ref	
 25-30			0.90 (0.72, 1.12)	0.33	0.88 (0.70, 1.10)	0.26	
 ≥30			0.95 (0.79, 1.15)	0.6	0.87 (0.72, 1.05)	0.15	
Smoking status							
 Never					ref	ref	
 Former					1.45 (1.17, 1.81)	0.001	
 Now					1.54 (1.23, 1.93)	<0.001	
Drinking status							
 Never					ref	ref	
 Former					1.36 (1.02, 1.81)	0.04	
 Now					1.15 (0.87, 1.52)	0.31	
Hypertension							
 No					ref	ref	
 Yes					1.41 (1.22, 1.63)	<0.0001	
Diabetes							
 No					ref	ref	
 IGT					1.05 (0.72, 1.52)	0.81	
 IFG					0.93 (0.59, 1.47)	0.76	
 DM					1.09 (0.90, 1.33)	0.37	
Model 1, unadjusted crude model. Model 2, adjusted for demographic characteristics (sex, age group, race, education, marital status) and BMI category. Model 3, adjusted for demographic characteristics (sex, age group, race, education, marital status), BMI category, smoking status, drinking status, hypertension and diabetes. BMI, body mass index; DM, diabetes mellitus; IFG, impaired fasting glycaemia; IGT, impaired glucose tolerance

As shown in Table 3, the logistic regression analyses also demonstrated a positive relationship between psoriasis and the incidence of skin cancer. In model 1 (OR = 2.89; 95% CI: 1.57–5.32), model 2 (OR = 2.41; 95% CI: 1.26–4.60), and model 3 (OR = 2.21; 95% CI: 1.14–4.31), the risk of skin cancer was higher in participants with psoriasis compared to those without psoriasis. A multivariate regression analysis showed that sex, age, race, education level, BMI category, and smoking status were significantly related to cancer. Hypertension (OR = 1.40; 95% CI: 1.08–1.82) was also significantly associated with an elevated risk of skin cancer. We also investigated the relationship between psoriasis and other common cancers among adults aged 20 years or older [Supplementary Table S1]. However, psoriasis was not associated with an elevated risk of prostate cancer, cervix (cervical) cancer, breast cancer, and colon cancer.

Table 3 Relationship between psoriasis and skin cancer among adults aged 20 years or older

Variable	Model 1	Model 2	Model 3	
			
OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P	
Psoriasis							
 No	ref	ref	ref	ref	ref	ref	
 Yes	2.89 (1.57, 5.32)	<0.001	2.41 (1.26, 4.60)	0.01	2.21 (1.14, 4.31)	0.02	
Sex							
 Female			ref	ref	ref	ref	
 Male			1.48 (1.11, 1.98)	0.01	1.40 (1.04, 1.87)	0.03	
Age group							
 ≤49			ref	ref	ref	ref	
 50-65			5.39 (3.36, 8.63)	<0.0001	4.75 (2.89, 7.80)	<0.0001	
 ≥65			16.08 (10.23, 25.28)	<0.0001	12.71 (7.38, 21.89)	<0.0001	
Race							
 Hispanic			ref	ref	ref	ref	
 Non-Hispanic White			6.75 (2.88, 15.81)	<0.0001	6.43 (2.72, 15.20)	<0.0001	
 Non-Hispanic Black			0.19 (0.04, 0.82)	0.03	0.18 (0.04, 0.80)	0.03	
 Mexican American			0.28 (0.07, 1.13)	0.07	0.29 (0.07, 1.16)	0.08	
 Other			0.96 (0.21, 4.38)	0.96	0.94 (0.20, 4.45)	0.94	
Education							
 Less than high school			ref	ref	ref	ref	
 High school or equivalent			0.97 (0.53, 1.78)	0.93	0.98 (0.52, 1.82)	0.94	
 Some college or AA degree			1.51 (0.88, 2.62)	0.13	1.57 (0.89, 2.78)	0.12	
 College graduate or above			2.02 (1.19, 3.44)	0.01	2.16 (1.27, 3.69)	0.01	
Marital status							
 Married			ref	ref	ref	ref	
 Never married			0.61 (0.30, 1.21)	0.15	0.65 (0.32, 1.31)	0.22	
 Living with partner			0.56 (0.21, 1.45)	0.22	0.55 (0.20, 1.47)	0.22	
 Other			1.06 (0.74, 1.51)	0.75	1.06 (0.73, 1.53)	0.75	
BMI category							
 <25			ref	ref	ref	ref	
 25-30			0.82 (0.58, 1.14)	0.23	0.77 (0.54, 1.09)	0.14	
 ≥30			0.76 (0.53, 1.07)	0.11	0.67 (0.45, 0.99)	0.05	
Smoking status							
 Never					ref	ref	
 Former					1.68 (1.14, 2.47)	0.01	
 Now					1.05 (0.60, 1.86)	0.85	
Drinking status							
 Never					ref	ref	
 Former					1.46 (0.84, 2.54)	0.18	
 Now					1.36 (0.73, 2.53)	0.33	
Hypertension							
 No					ref	ref	
 Yes					1.40 (1.08, 1.82)	0.01	
Diabetes							
 No					ref	ref	
 IGT					1.23 (0.66, 2.28)	0.5	
 IFG					0.80 (0.37, 1.73)	0.56	
 DM					0.96 (0.66, 1.40)	0.83	
Model 1, unadjusted crude model. Model 2, adjusted for demographic characteristics (sex, age group, race, education, marital status) and BMI category. Model 3, adjusted for demographic characteristics (sex, age group, race, education, marital status), BMI category, smoking status, drinking status, hypertension and diabetes. BMI, body mass index; DM, diabetes mellitus; IFG, impaired fasting glycaemia; IGT, impaired glucose tolerance

Supplementary Table S1 Relationship between psoriasis and other common cancer among adults aged 20 years or older

Variable	Prostate cancer	Breast cancer	Cervix (cervical) cancer	Colon cancer	
				
OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P	
Psoriasis									
 No	ref	ref	ref	ref	ref	ref	ref	ref	
 Yes	0.88 (0.21, 3.72)	0.86	1.19 (0.58, 2.43)	0.63	1.04 (0.40, 2.70)	0.93	0.71 (0.12, 4.04)	0.69	

To examine the impact of the presence of cancer and/or psoriasis on all-cause mortality, we divided participants into four groups: (i) those without cancer and psoriasis, (ii) those with psoriasis but without cancer, (iii) those with cancer but without psoriasis, and (iv) those with both cancer and psoriasis. The impact of psoriasis and cancer on all-cause mortality was analysed using time-to-event analyses. Figure 2 displays the Kaplan–Meier survival curves for participants, which showed a significant difference (log-rank, P < 0.0001) in all-cause mortality among the four groups, with the highest mortality rate observed in participants with both psoriasis and cancer.

Figure 2 The Kaplan-Meier survival curves for participants

The results of the weighted Cox proportional hazards regression analysis are shown in Table 4. In the crude analysis, participants with both psoriasis and cancer had an approximately 5.25-fold increase in all-cause mortality risk compared with the referent group (P < 0.0001). The risk of all-cause mortality remained significant after adjusting for demographic factors (model 2, P = 0.03) and full adjustment (model 3, P = 0.02). In model 3, compared with individuals without cancer and psoriasis, the all-cause mortality HRs were 1.25 (95% CI: 0.87–1.78) for individuals with psoriasis only, 1.48 (95% CI: 1.20–1.82) for participants with cancer only, and 2.28 (95% CI: 1.12–4.63) for individuals with both psoriasis and cancer.

Table 4 Association between psoriasis and cancer status and all-cause mortality

Variable	Model 1	Model 2	Model 3	
			
HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P	
Group							
 Neither psoriasis nor cancer	ref	ref	ref	ref	ref	ref	
 Only psoriasis	1.35 (0.96, 1.90)	0.08	1.30 (0.94, 1.79)	0.12	1.25 (0.87, 1.78)	0.23	
 Only cancer	3.68 (3.03, 4.46)	<0.0001	1.59 (1.28, 1.98)	<0.0001	1.48 (1.20, 1.82)	<0.001	
 Both psoriasis and cancer	5.25 (2.41, 11.42)	<0.0001	2.41 (1.09, 5.29)	0.03	2.28 (1.12, 4.63)	0.02	
Sex							
 Female			ref	ref	ref	ref	
 Male			1.50 (1.32, 1.70)	<0.0001	1.40 (1.24, 1.59)	<0.0001	
Age group							
 ≤49			ref	ref	ref	ref	
 50-65			4.50 (3.66, 5.53)	<0.0001	3.34 (2.69, 4.16)	<0.0001	
 ≥65			17.96 (14.46, 22.31)	<0.0001	11.89 (9.40,15.05)	<0.0001	
Race							
 Hispanic			ref	ref	ref	ref	
 Non-Hispanic White			1.81 (1.22, 2.69)	0.003	1.73 (1.22, 2.46)	0.002	
 Non-Hispanic Black			1.88 (1.31, 2.72)	<0.001	1.57 (1.10, 2.24)	0.01	
 Mexican American			1.21 (0.85, 1.74)	0.29	1.27 (0.91, 1.77)	0.16	
 Other			1.56 (0.97, 2.50)	0.07	1.36 (0.85, 2.16)	0.2	
Education							
 Less than high school			ref	ref	ref	ref	
 High school or equivalent			0.72 (0.61, 0.85)	<0.001	0.84 (0.72, 0.98)	0.03	
 Some college or AA degree			0.59 (0.51, 0.70)	<0.0001	0.74 (0.62, 0.87)	<0.001	
 College graduate or above			0.41 (0.33, 0.49)	<0.0001	0.63 (0.50, 0.78)	<0.0001	
Marital status							
 Married			ref	ref	ref	ref	
 Never married			1.79 (1.47, 2.17)	<0.0001	1.83 (1.49, 2.24)	<0.0001	
 Living with partner			1.90 (1.37, 2.63)	<0.001	1.73 (1.25, 2.40)	0.001	
 Other			2.06 (1.73, 2.45)	<0.0001	1.92 (1.62, 2.28)	<0.0001	
BMI category							
 <25			ref	ref	ref	ref	
 25-30			0.79 (0.66, 0.94)	0.01	0.73 (0.61, 0.86)	<0.001	
 ≥30			1.00 (0.86, 1.17)	0.99	0.80 (0.67, 0.94)	0.01	
Smoking status							
 Never					ref	ref	
 Former					1.24 (1.01, 1.51)	0.04	
 Now					2.17 (1.82, 2.58)	<0.0001	
Drinking status							
 Never					ref	ref	
 Former					1.49 (1.18, 1.88)	<0.001	
 Now					0.84 (0.68, 1.05)	0.12	
Hypertension							
 No					ref	ref	
 Yes					1.95 (1.66, 2.29)	<0.0001	
 Diabetes							
 No					ref	ref	
 IGT					1.16 (0.84, 1.59)	0.37	
 IFG					1.24 (0.93, 1.65)	0.15	
 DM					1.77 (1.48, 2.13)	<0.0001	
Model 1, unadjusted crude model. Model 2, adjusted for demographic characteristics (sex, age group, race, education, marital status) and BMI category. Model 3, adjusted for demographic characteristics (sex, age group, race, education, marital status), BMI category, smoking status, drinking status, hypertension and diabetes. BMI, body mass index; DM, diabetes mellitus; IFG, impaired fasting glycaemia; IGT, impaired glucose tolerance

Discussion

In the present study, we aimed to explore the connections between psoriasis, cancer, and mortality using the NHANES data collected between 2003–2006 and 2009–2014. Our findings indicate that patients with psoriasis face a heightened risk of cancer, especially skin cancer. In addition, individuals with both psoriasis and cancer face a significantly higher risk of all-cause mortality compared to those without either condition, even after accounting for demographic factors (sex, age, race, marital status, and education), smoking status, drinking status, BMI category, hypertension, and diabetes. These findings underscore the importance of targeted screening for cancer among individuals with psoriasis and provide robust evidence for further exploration in both basic and clinical research.

Psoriasis is a chronic, relapsing systemic inflammatory disease which is often accompanied by numerous comorbidities in addition to the skin lesions. Previous studies have shown that psoriasis may have multiple comorbidities including metabolic syndrome, diabetes, nonalcoholic fatty liver disease, depression, and cardiovascular disease.[1112] However, the association between psoriasis and cancer is controversial. Alex M Trafford and colleagues conducted a systematic review and meta-analysis of observational studies on the risk of cancer incidence in people with psoriasis.[13] However, psoriasis was significantly negatively associated with cancers (OR = 0.267) in a retrospective hospital-based case-control study.[1314] Given the substantial heterogeneity observed in this systematic review and meta-analysis, coupled with inconsistent findings in prior studies, further investigation is imperative to better understand the association between psoriasis and cancer. In the present study, we further demonstrated that psoriasis was associated with an increased risk of cancer. The risk of cancer in patients with psoriasis remains a cause of special concern due to the chronic inflammatory nature of the disease, the utilisation of immune-suppressive treatments, and an elevated prevalence of established risk factors for cancer, including smoking and obesity, all of which may increase the risk of carcinogenesis.[15]

It is important to note that the prevalence of different types of cancer in patients with psoriasis may vary. Lee et al.[16] evaluated the association of psoriasis with certain cancers using national statistics from Korea. The risk of cancer increased in the following order: prostate, thyroid, liver, ovarian, lung, leukemia, skin, multiple myeloma, lymphoma, and testicular. Chiesa Fuxench et al. conducted a comparative analysis, assessing both the overall risk of cancer and specific cancers of interest in a population-based cohort study conducted in the Health Improvement Network. This association was primarily driven by nonmelanoma skin cancer, lymphoma, and lung cancer. Nevertheless, no significant association was identified concerning cancers of the breast, colon, prostate, or leukaemia.[15] In our study, we observed that psoriasis was not linked to an elevated risk of prostate cancer, breast cancer, cervical cancer, or colon cancer. Therefore, the relationship between psoriasis and certain cancers remains unclear and necessitates further prospective studies. Despite these inconsistent findings, periodic screening for cancer risk is recommended in patients with psoriasis.

Worldwide, skin cancer affects millions of people yearly and is broadly classified into melanoma and nonmelanoma types of skin cancer.[17] Psoriasis is associated with a significant risk of malignancies, especially skin tumours.[7] Over the years, scientists have tried to assess the extent to which psoriasis can increase the risk of developing skin cancer.[18] Polesie S and Gillstedt M found that patients with psoriasis were at an increased risk for cutaneous malignant melanoma, including in situ melanoma.[19] However, there are also studies that come to the opposite conclusion. Paradisi A and colleagues reported that patients with psoriasis had a 16% lower probability of having nonmelanoma skin cancer when compared to a group of nondermatological patients.[20] A recent study by Yu et al.[21] suggested no causal association between psoriasis and the genetic risk of skin cancer. A comprehensive review conducted by Balda et al.[7] holds the view that skin cancer was explained in the context of the several psoriasis medications that increase the likelihood of skin cancer. The biological treatments targeting the underlying mechanisms of psoriasis can potentially alleviate the inflammatory burden and reduce the risk of developing cancer.[22] Our findings suggested that the risk of skin cancer was higher in participants with psoriasis compared to those without psoriasis. Further observational studies are required to elucidate the relationship among psoriasis and skin cancer.

Previous studies have explored the association between psoriasis and mortality. Trafford et al.[13] conducted a systematic review and meta-analysis of observational studies to assess the risk of mortality in individuals with psoriasis. Of note, only 7 cohort studies considered the risk of overall cancer mortality in people with psoriasis. Although four studies of severe psoriasis produced a pooled RR of 1.22 (95% CI, 1.08–1.38) with considerable heterogeneity, pooling of the two studies which reported mortality risk estimates from all cancers in people with psoriasis of all severities found no difference in risk of cancer mortality.[13] Gelfand et al.[23] reported that severe psoriasis, but not mild psoriasis, was associated with an elevated risk of death. A population-based cohort study in the UK uncovered that while all-cause mortality rates have decreased over a 15-year period for both the general population and individuals with psoriasis, the risk of all-cause mortality remains higher for those with psoriasis compared to those without the condition.[24] Notably, two meta-analyses have independently demonstrated that psoriasis is associated with an increased risk of mortality.[2526]

Our study builds upon previous longitudinal studies that have explored the link between psoriasis and mortality. To further elucidate the combined impact of psoriasis and cancer on mortality, we divided all patients into four groups. The all-cause mortality of the population with psoriasis was higher compared to those without psoriasis, but the difference did not reach statistical significance. On the other hand, the all-cause mortality of individuals with cancer was significantly higher compared to those without cancer. When psoriasis was present alongside cancer, there was a significant increase in mortality, which was also higher compared to patients with cancer alone. The comorbidity of psoriasis and cancer in relation to mortality is partially explained by the high prevalence of cardiovascular, infectious, and neoplastic disorders among psoriasis patients.[27] In addition, the use of biological agents has also played a role in reducing mortality. A retrospective study based on the NHANSE database by Semenov et al.[27] showed a lower risk of death from psoriasis in the US population compared to a European cohort. The biologics utilisation in the United Kingdom is reported to be half that in the United States.[2829] One of the possible hypotheses is that the cardioprotective effects of systemic and biologic therapies for psoriasis potentially counteract the inflammatory process of psoriasis and, in turn, reduce the observed CVD mortality risk in the US population.[30]

In our study, the reduced survival of those with combined psoriasis and cancer is a major finding. It is important to note that the presence of psoriasis can act as a significant additional risk factor for all-cause mortality in the context of cancer. These findings have significant implications, suggesting that screening for cancer could play a crucial role in enhancing the lifespan of individuals with psoriasis. The underlying mechanisms connecting psoriasis, cancer, and mortality remain unclear. The presence of these multiple comorbidities in psoriasis patients may contribute to an increased risk of all-cause mortality.

As one of the most extensive investigations to date exploring the combined impact of psoriasis and cancer on the risk of mortality, the study has several notable strengths. Firstly, our analysis employed nationally representative survey data, providing a comprehensive and extended follow-up period. Furthermore, we applied appropriate statistical procedures and sample weights to obtain all-cause mortality that are reflective of the general population. The robust sample size of NHANES allowed for adjustment for potential confounding variables. Secondly, the participants in our study were randomly sampled from the general population, ensuring the representativeness of our findings. Thus, our results can be extrapolated to the broader US population with confidence.

Our findings should be interpreted in light of certain limitations. Firstly, the cross-sectional design of the NHANES data prevents us from establishing causality between psoriasis, cancer, and all-cause mortality. Secondly, despite efforts to adjust for relevant confounding variables, there may still be residual confounding from unmeasured or unknown factors. Thirdly, the lack of detailed information on the severity of psoriasis in the NHANES data hinders our ability to differentiate the association between all-cause mortality and different severity categories of psoriasis. Despite these constraints, our study revealed a positive association between psoriasis, cancer, and all-cause mortality. Future research with larger sample sizes and more precise measurement methods is crucial to establishing a more definitive causal relationship between psoriasis, cancer, and all-cause mortality.

Conclusions

Our study uncovered a noteworthy and positive correlation between psoriasis, cancer, and all-cause mortality, indicating that individuals with both conditions face an increased risk of death. Further research is needed to gain a deeper understanding of the relationship between psoriasis, cancer, and all-cause mortality as well as to explore the potential benefits of therapeutic interventions for this specific population. The implementation of screening measures and proactive management strategies for psoriasis and cancer could potentially serve as an effective approach to reduce mortality risk, with potential implications for both clinical practice and public health.

Ethics approval and consent to participate

The protocols of NHANES were approved by the Institutional Review Board of the National Center for Health Statistics, CDC. Written informed consent was obtained from each participant before participation in the NHANES study. As the present study was a secondary analysis of NHANES data, which are publicly available, no institutional review board approval was necessary or obtained.

Financial support and sponsorship

This work was supported by the Zhejiang Province Traditional Chinese Medicine Research Fund Project (No. 2022ZB285).

Conflicts of interest

There are no conflicts of interest.

Acknowledgments

Thanks to Zhang Jing (Shanghai Tongren Hospital) for his work on the NHANES database. His outstanding work, nhanesR package and webpage, makes it easier for us to explore NHANES database. This work was supported by the Zhejiang Province Traditional Chinese Medicine Research Fund Project (No. 2022ZB285).
==== Refs
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