Cancer survivors require comprehensive health care due to higher incidence of various conditions, such as recurrence, second primary cancers, and chronic illness [1]. With their numbers rapidly increasing, cancer survivorship has become a critical medical and social issue [2]. Recently, it has also been suggested that cancer survivors are at risk of frailty and aging-related physiological decline, which are closely related to survival, long-term function, and quality of life [3]. In particular, given reports on the effectiveness of resistance training in improving lean body mass in cancer survivors [4], evaluations of muscle conditions, such as muscle volume and strength and endurance, are important starting points for treating muscle wasting in this population.

Handgrip strength (HGS) testing is widely used to assess overall muscle strength and physical frailty because it is straightforward, rapid, and inexpensive [5]. However, the findings remain controversial regarding whether the HGS of cancer survivors is lower than that of the general population, despite the fact that acute cancer treatment is known to reduce HGS [6]. HGS is significantly lower in esophageal [7] and metastatic breast cancer survivors [8], and longitudinal studies have shown a more rapid decline in HGS among cancer survivors [9,10]. Meanwhile, HGS was not significantly different in cancer survivors compared to healthy controls in other studies [11,12]. However, studies that addressed this topic were limited by small sample sizes [9-12], the use of specific cancer types [7-9], skewed age distributions [9,11], or by failure to consider potential mediators such as depressive mood [13]. In this Korean study, we examine association between HGS and cancer history, with considering times after a diagnosis of cancer, using nationwide data.

1. Study design and participants

The data used in this study was extracted from the Korean National Health and Nutrition Examination Survey (KNHANES 2014–2019) results. KNHANES is a nationwide population-based survey conducted annually by the Korean Ministry of Health and Welfare on subjects randomly selected using a stratified, multistage, probability sampling design. Interviews and examinations were conducted in specifically designed and equipped mobile centers. All subjects that participated in KNHANES provided written informed consent. Detailed information on KNHANES is provided elsewhere [14]. The study received approval form the Institutional Review Board of Gachon University Gil Medical Center, in accordance with established ethical standards (IRB no. GFIRB2021-481).

Initially, we identified 32,221 subjects aged 19 to 79 years old with data on HGS (age at cancer diagnosis was not specified for individuals ≥80 years old). Times from cancer diagnoses were calculated by subtracting ages at diagnoses from ages at survey completion. For the analysis, subjects were dichotomized about 5 years after diagnosis into short- and long-term cancer survivors. Individuals diagnosed with depression were excluded from the analysis, as depression is closely associated with HGS among underlying conditions [15]. After excluding 805 patients with current depression, 31,416 subjects (29,932 subjects without a cancer history, 561 short-term cancer survivors, and 923 long-term cancer survivors) were included in the analysis.

2. Data collection

The outcome variable of interest was HGS, which was measured using a digital grip strength dynamometer (TKK 5401; Takei Scientific Instruments Co., Ltd., Tokyo, Japan), following standard measurement guideline. The maximal HGS value of the dominant hand was used in the analysis.

Information on demographic characteristics (age, sex, educational attainment, marital status, economic status, and current job status), health-related habits (smoking history, alcohol consumption, and aerobic exercise), and history of disease as diagnosed by a physician (hypertension, type 2 diabetes, and cardiovascular disease such as angina pectoris, myocardial infarction, or stroke) was collected during the health interview. Educational level was categorized as “middle school or lower” and “high school or beyond”. Unmarried statuses classified as “single” or “divorced/separated/widowed”. Average family size-adjusted mean monthly income was used as an indicator of economic status. Current smokers were defined as individuals who smoked cigarettes at time of interview. Those that drank more than twice per week were defined as frequent drinkers. Aerobic exercise was defined as ≥2.5 hours/week of moderate-intensity activities, ≥1.25 hours/week of high-intensity activities, or a considered combination of activities. Obesity was defined as a body mass index ≥25 kg/m², according to the World Health Organization’s recommendation for Asians [16]. To assess depressive mood, we used responses (yes/no) to the questionnaire item: “Have you experienced sadness or despair for more than 2 weeks continuously during the past year?”.

3. Statistical analysis

Means±standard deviations or numbers (percentages) were used to describe subject characteristics. One-way analysis of variance test was applied to compare HGS of each group. Multivariate regression models adjusted for potential confounders were used to evaluate and compare HGS of short-term and long-term cancer survivors to individuals without a history of cancer. The analysis was performed using STATA MP 17.0 (Stata Corp., College Station, TX, USA). All statistical tests were two-sided, and P-values of < 0.05 were considered statistically significant.

Subject characteristics are presented in Table 1, which compares three groups: short-term cancer survivors, long-term cancer survivors, and individuals without a cancer history. Significanct differences were observed among the three groups.

Table 1 . Participant characteristics according to time after cancer diagnosis.

	Cancer survivors			P-value
	No cancer history	<5 years after cancer	≥5 years after cancer
Numbers	29,932	561	923
Demographics
Age (yr)	49.3±16.0	59.0±12.2	62.2±11.2	<0.001
Sex (female)	16,303 (54.5)	329 (58.6)	590 (63.9)	<0.001
Low education level	7,627 (25.5)	235 (41.9)	412 (44.6)	<0.001
Low-income level	12,151 (40.6)	266 (47.4)	496 (53.7)	<0.001
No current job	10,173 (34.0)	296 (52.8)	509 (55.1)	<0.001
Health-related habits
Current smoker	5,640 (18.8)	45 (8.0)	72 (7.8)	<0.001
Frequent drinker	6,740 (22.5)	69 (12.3)	138 (15.0)	<0.001
Aerobic exercise	13,124 (43.8)	250 (44.6)	366 (39.7)	<0.001
Comorbidities
Obesity	10,367 (34.6)	164 (29.2)	282 (30.6)	0.001
Hypertension	6,307 (21.1)	192 (34.2)	322 (34.9)	<0.001
Type 2 diabetes	2,429 (8.1)	83 (14.8)	146 (15.8)	<0.001
Cardiovascular disease*	1,156 (3.9)	26 (4.6)	68 (7.4)	<0.001
Depressive mood	4,031 (13.5)	102 (18.2)	149 (16.1)	<0.001
Handgrip strength (kg)	31.5±10.4	28.9±8.7	27.7±8.6	<0.001

Data are presented as number only, means±standard deviations, or numbers (%). *Includes angina pectoris, myocardial infarction, and stroke..

Table 2 shows the ß coefficients of HGS for short- and long-term cancer survivors as compared with subjects without a cancer history. In the crude model, short- and long-term cancer survivors had significantly lower HGSs than those without a cancer history (2.62 kg for short-term cancer survivors and 1.88 kg for long-term cancer survivors). However, these significances were lost in adjusted models.

Table 2 . Handgrip strengths (kg) according to time after cancer diagnosis as compared with subjects without a cancer history.

	Unadjusted			Age- and sex-adjusted			Multivariate* adjusted
	ß (95% CI)	P-value		ß (95% CI)	P-value		ß (95% CI)	P-value
Within 5 years of cancer diagnosis	−2.62 (‒3.49-‒1.75)	<0.001		−0.52 (−1.04-−0.01)	0.047		−0.25 (−0.79-0.29)	0.361
After 5 years of cancer diagnosis	−1.88 (‒2.22-‒1.54)	<0.001		−0.17 (−0.38-0.03)	0.092		0.02 (−0.19-0.24)	0.832

ß, regression coefficient; CI, confidence interval. *Includes age, sex, education level, economic status, current job, current smoking, frequent drinking, aerobic exercise, obesity, hypertension, type 2 diabetes, cardiovascular disease (angina pectoris, myocardial infarction, or stroke), and depressive mood. Aerobic exercise as defined by Korean National Health and Nutrition Examination Survey was ≥2.5 hours/week of moderate intensity activities, or a considered combination of activities..

It is plausible that biological mechanisms induced by cancer and subsequent treatment cause functional decline [3]. However, in contrast to childhood cancer survivors [17], research on functional decline among survivors of adult-onset cancers is limited, especially on functional decline as determined by HGS measurements. Although HGS might be a useful tool in terms of assessing outcomes among cancer survivors [8,18,19], we could not find association between HGS cancer history.

The Baltimore Longitudinal Study on Aging (BLSA) reported, through univariate analysis, that a history of cancer was associated with 1.5 greater odds ratio of a weak HGS (95% confidence interval, 1.1–1.9) [10]. However, BLSA participants were healthy and free from critical comorbidities, whereas more potential covariates, including depressive mood, were included in the present study [13]. In particular, depression is an important covariate as it is closely related to physical frailty and can significantly impact muscle strength assessment such as HGS. In our multivariate analysis, covariates other than cancer history were found to be associated with HGS (data not shown), suggesting that other factors likely explain HGS decline in cancer survivors. Given the controversy in previous studies, there is a need for large scale studies and integrated data analyses to better understand the relationship between HGS and cancer history.

Cancer survivorship in middle-aged and older adults holds particular significance due to the interplay between aging, frailty, and cancer-related muscle decline. As individual ages, the risk of developing cancer increases, making it crucial to understand how survivorship impacts this demographic’s physical health. HGS is a simple marker for detecting frailty, especially in older adults, and can predict future disability and mortality [15]. Given that the average age of cancer diagnosis often falls in the later stages of life, understanding HGS trends in this population can help tailor better rehabilitation and healthcare strategies. Despite the lack of significant findings in this study, the nuanced implications of HGS on the quality of life and overall vitality in older cancer survivors necessitate further exploration.

This study has several limitations. First, the cross-sectional nature of KNHANES did not allow inferences to be drawn regarding temporal relationships, as single HGS measurements cannot reflect longitudinal changes. Second, residual confounding is possible because clinical information on cancer type, stage, therapeutic modalities, and the presence or absence of resistance exercise were not considered. Nevertheless, this is the largest study to compare the HGSs of cancer survivors with those of a general population. Our findings suggest that HGS may be not a proper indicator of muscle weakness among cancer survivors. A rigorously designed longitudinal study that includes detailed clinical information and other ethnicities is needed to confirm or refute our findings.

This research was supported by Gachon University Gil Medical Center under Grant FRD2021-14.

This research was supported by a grant of the Korea Health Promotion R&D Project, funded by Ministry of Health & Welfare, Republic of Korea (grant number: HS23C0045).

YJ Lee is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.