Prevalence and associated risk factors of prostate cancer among a large Chinese population

doi:10.21203/rs.3.rs-4058045/v1

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Prevalence and associated risk factors of prostate cancer among a large Chinese population

https://doi.org/10.21203/rs.3.rs-4058045/v1

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published 01 Nov, 2024

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Prostate cancer (PCa) is one of the most important health problems among elderly in China, with the increasingly serious problem of aging. A cross-sectional survey was conducted in eastern China from 2022 to 2023. Recruitment included a total of 70342 participants aged 60 or older. Socio demographic profiles, examinations were administrated. Age-standardised prevalence rates were calculated by a direct method with a standard population. T test and chi-square test were used to compare the statistical differences. Multivariate regression models were used to identify the risk factors of PCa. Overall, the crude and age-adjusted PCa prevalence is 0.93% and 0.91%, respectively in eastern China. When we adjusted all the co-variables, it showed that elderly, smoking, having a higher BMI, smoking were associated with PCa. Faced with the epidemiological transition, we need innovative strategies to control and prevent PCa. Conducting early screening among male population in community health service centers in eastern of China, especially among population with high associated risk factors, such as elderly, overweight or obese and so on, and conducting community-based intervention programs might be helpful to address this serious problem.

Biological sciences/Cancer/Cancer epidemiology

Health sciences/Health care/Disease prevention

Health sciences/Health care/Public health

Prostate cancer (PCa) is one of the most common malignant tumors of urogenital system. According to the Global Cancer Statistics Report published by the WHO International Agency for Research on Cancer (2022), there were 1,466,718 new cases of PCa in the world, ranking fourth after lung cancer, breast cancer and colorectum cancer. PCa deaths were 396,773 cases, the death rate ranked eighth.¹ Recently, the National Cancer Center announced the latest situation of the burden of malignant tumors in China in 2022, among which the incidence cases of PCa is 134,200, ranking ninth among all cancers in China. The standardized incidence was 9.68 (1/10⁵), ranking sixth among male malignant tumors. 47,500 people died, with a mortality rate of 6.59 (1/10⁵), ranking seventh among male malignant tumors.² Both morbidity and mortality rankings have increased.³ From the perspective of the world, the incidence of PCa has obvious geographical and ethnic differences, in Australia/New Zealand, North America and Europe, the incidence is high, with the incidence of more than 85/100,000. The lowest incidence is found in Asia, where the incidence ranges from 4.5 to 10.5/100,000. Although the incidence of PCa in China is much lower than that in Europe and America, it has been increasing year by year in recent years. The main reasons for the increase in the incidence of PCa in China may be aging population, changes in people's lifestyle, and lacing suitable PCa screening methods is also an important reason.

The etiology and pathogenesis of PCa are very complex, and its exact etiology is not clear. Etiological studies have shown that PCa is closely related to genetics, age, exogenous factors (such as environmental factors, dietary habits). Epidemiological data show that the incidence of PCa increases significantly after Asian immigrants to the United States, suggesting that exogenous factors such as geographical environment and dietary habits also affect the incidence of PCa. At present, the exogenous risk factors of PCa are still under study, some factors are still controversial, and there is no clear drug intervention or dietary method to prevent PCa.

The prevalence of PCa is closely related to age, and its incidence increases with age, the older the incidence is higher, and the highest incidence age is 65–80 years old.⁴ Zhejiang province, located in eastern China, has an aged population of approximately 12.07 million, accounting for 18.7% of the total population in 2020.⁵ There is an urgent need for a study to get the PCa prevalence, including the associated risk factors, which is lack in eastern China.⁶ In this study, we aim to collect and describe PCa prevalence in eastern China. And we also want to identify known risk factors for PCa.

Population

This investigation was characterized as an observational study of cross-sectional type, using exploratory methods such as surveys and blood collection, carried out in eastern China from June 2022 to August 2023. Inclusion criteria were men who were 60 years or more that lived in eastern China, and who willing to undergo PCa screening. The exclusion criteria included of complicated with other malignancies, with history of prostate surgery, severe nervous system diseases or mental diseases, having cognitive disorders and could not complete study assessment independently. The total sample included 74,098, and there was a follow-up after 4 months. After removing the cases with incomplete information, there were 70,342 participants in the final analysis set, including 45,305 in 2022 and 25037 in 2023. And there were no significant differences among main demographic variables between responders and nonresponders. Flow chart was showed in Fig. 1.

Data Collection

Data collection included basic information, physical examinations and laboratory tests. Basic information was collected using questionnaires by trained nursers, which including of individual factors such as age, education levels, behavior habits and so on. Physical examination included height, weight, waistline, blood pressure, heart rate and so on. Laboratory tests included of prostate-specific antigen (PSA), serum carcinoembryonic antigen (CEA), carbohydrate antigen 19 − 9 (CA19-9), fasting blood glucose (FBG), blood lipid level and urine tests.

Measures

The survey and tests was conducted by trained nursers or general practitioners in community health service centers or participants’ residences. Alcohol and tobacco consumption was self-reported by asking questions about the consumption, alcohol consumption was defined as yes if the consumption was at least once a week. Smoking was defined as continuous or cumulative smoking for 6 months or more. Regular exercise was defined as having exercise 3 days a week or more. Hypertension were defined as systolic blood pressure (SBP) equaled to 140 mm Hg or more and/or diastolic blood pressure (DBP) equaled to 90 mmHg or more with BP measured 3 times on diferent days, or having a history of hypertension or taking antihypertensive drugs within 2 weeks.^{7, 8} Overweight was defined as body mass index (BMI) ≥ 24 kg/m² and < 28 kg/m², obesity was defined as BMI<28kg/m². ⁹

Diabete was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L ¹⁰. Dyslipemia was defined as high when one of the indexes of serum triglycerides (TG), serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) was abnormal.⁹ Serum carcinoembryonic antigen (CEA) was high if CEA ≥ 5 ug/L, alpha fetal protein (AFP) was high if AFP ≥ 9 ng/ml, carbohydrate antigen 19 − 9 (CA19-9) was high if CA19-9 ≥ 39 ug/L.

Blood samples were collected in the morning using vacuum blood collection tubes with 10 mL plastic clot activator with a diameter of 16 × 100 mm. After venipuncture, the blood was stored, to be subsequently centrifuged in pairs for 10 min at 3000 rpm, and stored in an ice box and then transferred to the laboratory that performed the sample processing by immunoassay analyzer.¹⁰ A PSA level equal to or greater than 4 ng/mL was considered high.⁴

Quality control

When measuring height and weight, participants were asked to wear light clothing, no shoes. Blood pressure was measured in a sitting position, resting for at least 5 minutes before measurement, blood pressure was measured twice on the right upper arm using a standard electronic sphygmomanometer (Omron HEM-7430). If the difference between two readings was greater than 10mm Hg, a third measurement was taken and the average of the last two readings was used.

Ethics

The study protocol was reviewed and approved by the Institutional Ethics Committee of Zhuji Center for Disease Control and Prevention. The participants were informed about the objectives and methods of the study. They were informed that their participation was totally voluntary and that they could withdraw from the study at any time without citing any reason. Written and signed or thumb printed informed consent was obtained from those who agreed to participate, or from their guardians. All methods used in this research were performed in accordance with the relevant guidelines and regulations.

Statistical Analysis

To make the database, the software Epidata (version 3.1) was used, and for the analyses, the statistical software SAS 9.4 was used. The normality of the data was verified by the Kolmogorov-Smirnov test for all analyzed variables. Frequency (percentage) description was used for counting data, and mean and standard deviation description was used for measuring data, so as to study the socio-demographic characteristics. Age-standardised prevalence rates were calculated by a direct method with a standard population (the 7th population census in Zhejiang, 2020). T test and chi-square test were used to compare the statistical differences.

To identify the factors associated with PCa, crude and multivariate regression models were performed with estimates of the odd ratios (OR). The crude models were constructed containing each of the independent variables and the response variable of PCa (yes/no). And the associations were assessed using multivariate models adjusted for the covariates age, education levels, behavior habits and so on. Significance level was set at p < 0.05 for all hypothesis tests.

Baseline information

The total sample included 70,342 participants, including 45,305 ones collected in 2022 and 25,037 in 2023, baseline demographics for the study were displayed in Table 1. The median age of the participants was 70 years, and most of them had a education level of primary school or middle school. 32.64% participants had a lifestyle of smoking and 42.53% drinking. The median PSA value was 2.96 ng/ml. More details were showed in Table 1.

Table 1

Participants’ characteristics (n = 70342)
Items	Subjects
Age (years), mean ± SD	70.46 ± 6.71
Education levels, No. (%)
Illiterate	6901 (9.81)
Primary school	39961 (56.81)
Middle school	18887 (26.85)
High school or above	4593 (6.53)
Smoker, No. (%)	22916 (32.64)
Drinker, No. (%)	29723 (42.53)
High-salt diet, No. (%)	15977 (22.71)
Meat-based diet, No. (%)	525 (0.75)
High oil diet, No. (%)	394 (0.56)
High-sugar diet, No. (%)	187 (0.27)
Regular exercise, No. (%)	12381 (17.64)
Waistline (cm), mean ± SD	85.91 ± 8.64
BMI (kg/m3), mean ± SD	23.96 ± 3.15
PSA (ng/mL), mean ± SD	2.96 ± 44.71
PSA, No. (%)
<4 ng/mL	60913 (86.6)
4–10 ng/mL	7338 (10.43)
>10 ng/mL	2091 (2.97)
Hypertension, No. (%)	29498 (41.94)
Diabetes, No. (%)	8068 (11.47)
SBP (mmHg), mean ± SD	137.02 ± 17.53
DBP (mmHg), mean ± SD	80.48 ± 9.85
FBG (mmol/L), mean ± SD	5.82 ± 4.32
TC (mmol/L), mean ± SD	4.75 ± 1.89
TG (mmol/L), mean ± SD	1.52 ± 1.21
HDL (mmol/L), mean ± SD	1.46 ± 0.81
LDL (mmol/L), mean ± SD	2.77 ± 1.51
CEA (ug/L), mean ± SD	3.62 ± 25.32
AFP (IU/mL), mean ± SD	3.52 ± 19.73
CA19-9 (U/ml), mean ± SD	14.55 ± 57.37
Note: SD, standard deviation; PSA, prostate-specific antigen; SBP, systolic blood pressure; DBP, Diastolic blood pressure; FBG, fasting blood glucose; TC, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein; LDL, low density lipoprotein; CEA, serum carcinoembryonic antigen; AFP, alpha fetal protein; CA19-9, carbohydrate antigen 19 − 9.

Prevalence of of prostate cancer by subgroups

Among the 70,342 cases, there were 655 participants with PCa, the crude prevalence was 0.93%, and the age-standardised prevalence was 0.91%. Table 2 showed the results of the stratification analysis on the main demographic variables. In terms of age, the senior groups (71–80 years, 80 years or more) had higher prevalence. In terms of socioeconomic stratification factors, those who had a habit of smoking or drinking were faced with a higher prevalence.

Table 2

PCa prevalence among a elderly population stratified by demographic characteristics
Variables	Prostate cancer
Variables	N	Prevalence	p value
Age (years)			< 0.0001
60–70	219	0.57
71–80	333	1.29
81 or above	83	1.65
Education levels			0.352
Illiterate	18	0.26
Primary school	431	1.08
Middle school	197	1.05
High school or above	36	0.78
BMI (kg/m3)			0.1587
<18.5	15	0.63
18.5–23.9	300	0.88
24-27.9	271	0.99
≥28	69	1.02
Smoker			< 0.0001
Yes	238	1.04
No	327	0.69
Drinker			0.0022
Yes	306	1.03
No	321	0.8
High-salt diet			0.693
Yes	153	0.96
No	502	0.92
Regular exercise			0.1425
Yes	112	0.91
No	606	1.05
Hypertension			0.5084
Yes	283	0.96
No	372	0.91
Diabetes			0.1609
Yes	64	0.79
No	591	0.95
Dyslipemia			0.4242
Yes	341	0.96
No	314	0.9

Associated risk factors of prostate cancer

Table 3 described the associated risk factors of prostate cancer. Logistic regression models including crude model and adjusted model were used to assess factors associated with PCa, respectively. When we adjusted all the co-variables, the correlation was slightly stronger. It showed that elderly (71 years or more compared with 60 to 70 years), smoking, having a higher BMI (24 kg/m³ or more compared with less than 24 kg/m³), higher PSA (4 ng/ml or more compared with less than 4 ng/ml), smoking, higher CA19-9 were associated with PCa (Table 3).

Table 3

Crude and multivariate odd ratio (OR) for independent in relation to PCa
Variables	Crude analysis		Multivariate analysis
	OR [CI 95%]	p*	OR [CI 95%]	p**
Age (years)
60–70	1		1
71–80	1.79 (1.54–2.09)	< 0.0001	1.64 (1.37–1.95)	< 0.0001
81 or above	1.90 (1.51–2.39)	< 0.0001	1.32 (1.01–1.73)	0.0459
Education levels
Illiterate	1		1
Primary school	1.17 (0.78–1.76)	0.4524	1.02 (0.67–1.55)	0.9383
Middle school	1.13 (0.62–2.06)	0.6876	0.91 (0.49–1.69)	0.7716
High school or above	0.84 (0.21–3.39)	0.807	0.63 (0.15–2.60)	0.5186
BMI (kg/m³)
<24	1		1
24-27.9	1.12 (0.96–1.31)	0.168	1.19 (1.01–1.42)	0.042
≥28	1.14 (0.87–1.43)	0.4	1.35 (1.03–1.78)	0.0312
PSA, No. (%)
<4 ng/ml	1
4–10 ng/ml	1.37 (1.10–1.72)	< 0.0001	2.29 (1.81–2.91)	< 0.0001
>10 ng/ml	24.06 (20.43–28.33)	< 0.0001	25.37 (21.22–30.34)	< 0.0001
Smoker
No	1		1
Yes	1.54 (1.29–1.85)	< 0.0001	1.41 (1.17–1.70)	0.0004
Drinker
No	1		1
Yes	0.92 (0.87–1.97)	0.569	0.97 (0.91–1.02)	0.2314
High-salt diet
No	1		1
Yes	0.96 (0.80–1.16)	0.6891	0.95 (0.79–1.14)	0.5809
Meat-based diet
No	1		1
Yes	0.20 (0.03–1.44)	0.11	0.20 (0.03–1.41)	0.105
High oil diet
No	1		1
Yes	1.37 (0.57–3.33)	0.4834	1.41 (0.55–3.63)	0.476
High-sugar diet
No	1
Yes	1.15 (0.29–4.65)	0.8437	0.95 (0.22–4.15)	0.9595
Regular exercise
No	1		1
Yes	1.16 (0.96–1.40)	0.1367	1.10 (0.90–1.34)	0.3721
Hypertension
No	1		1
Yes	1.05 (0.90–1.23)	0.5078	0.96 (0.82–1.13)	0.6081
Diabetes
No	1		1
Yes	0.84 (0.64–1.08)	0.1712	0.82 (0.63–1.08)	0.1541
Dyslipemia
No	1		1
Yes	1.06 (0.91–1.24)	0.4244	1.08 (0.92–1.27)	0.3648
CEA
<5	1		1
≥ 5	1.29 (0.99–1.68)	0.056	1.16 (0.88–1.53)	0.295
AFP
<9	1		1
≥ 9	0.96 (0.51–1.79)	0.8907	0.90 (0.47–1.72)	0.757
CA19-9
<39	1		1
≥39	1.13 (0.66–1.91)	0.6643	1.79 (1.08–2.94)	0.0231
Note: PSA, prostate-specific antigen; CEA, serum carcinoembryonic antigen; AFP, alpha fetal protein; CA19-9, carbohydrate antigen 19 − 9.

Prostate cancer is a significant health concern in eastern China. The overall prevalence of PCa was 0.93%, and the age-standardised prevalence was 0.91%, which was lower than Canada (3.32%) ¹¹, France (1.8%) ¹² and Pakistan (5.20%) .¹³ This disparity may be attributable to variations in research techniques, sample size, social, environmental, and genetic factors, and the universal definition of prostate cancer. Our study aimed to give helpful information about prostate cancer to the health authorities so that something can be done to prevent deadly diseases like PCa.

The results of this study suggested that the prevalence of PCa was closely related to age, and its prevalence increased with age, the older the age, the higher the incidence, which was also proved by other studies. ^{11, 14, 15} The habit of tobacco consumption was showed as an associated risk factor of PCa in this study, another study also showed that a higher number of cigarettes per day to use was associated with a 30% higher risk of dying from PCa.^{16, 17} But a study showed that current cigarette smoking was inversely associated with incident PCa, which gave a controversial conclusion. ^{16, 17, 18} Heterogeneity present within the different studies precluded drawing conclusions to contemporary patients. Alcohol was showed associated with PCa in other studies¹⁹, but not showed a significant meaning in the multivariate regression model of this study, although there was a higher PCa prevalence in the drinking group compared with non-drinking one. One of the reasons might be that recent abstainers might have been included in the abstainer group. In our study, it showed that higher BMI (24 kg/m³ or more compared with less than 24 kg/m³) were associated with PCa. Another study showed that the estimated OR for PCa for a 5 kg/m² increase in BMI was 0.98 (95% CI: 0.95–1.01).²⁰

Higher PSA values (4 ng/ml or more compared with less than 4 ng/ml) were associated with PCa prevalence in our study, which had been confirmed in many other studies .^{10, 14} PSA was a single chain glycoprotein with serine protease activity synthesized and secreted by prostate acinar and duct epithelial cells. Under normal physiological conditions, PSA was mainly limited to prostate tissue, and serum PSA was maintained at a low concentration level. There were two forms of PSA in serum, some of which (10%-40%) were free PSA. A portion (60% -90%) was bound to α1-antichymotrypsin, and a small amount was bound to α2-macroglobulin, which was called complex PSA.⁴ The sum of free PSA and complex PSA was usually called total serum PSA. When the prostate became cancerous, after the normal tissue was destroyed, a large amount of PSA entered the blood circulation of the body and the serum PSA increased. PSA had advantages as an early screening tool for PCa.

PCa screening has been widely carried out in Europe and the United States. For example, the death rate from PCa in the United States has declined in recent years, thanks in part to widespread and stringent prostate cancer screening policies.⁴ Of course, as more and more advanced PCa is found and treated, the proportion of early PCa is increasing, and there may be a small amount of overdiagnosis and overtreatment. Therefore, there is currently a great deal of controversy in Europe and the United States about population-based prostate cancer screening, and some policy guidelines would have the opposite situation. However, in China, because large-scale PCa screening has not begun, there should be a considerable number of highly aggressive or advanced PCa cases in the population. Therefore, at the present stage in our country, it is very necessary to carry out PCa screening based on PSA.

Our study had several strengths and limitations. The main strength included that it was one of very few surveys about PCa prevalence and associated factors among a larger population in China. But some limitations needed to be mentioned in this study. First of all, this study was a cross-sectional survey, which was failed to establish cause-and-effect relationship between the observed associations. Second, some confounding variables including family history of diseases and family income were not included, and the definition of alcohol consumption was should more detailed. All of these called for further studies involving longer cohorts to verify our conclusion.

PCa prevalence was one of the most important health problems among elderly in eastern China, especially as the ageing population has become more and more serious. Faced with the epidemiological transition, we need innovative strategies to control and prevent PCa. Conducting early screening among male population in community health service centers, especially among population with high associated risk factors, such as elderly, overweight or obese and so on, and conducting community-based intervention programs might be helpful to address this serious problem.

Data availability

The data set of this study is available from the corresponding author upon request.

Funding information

This work was funded by special leading plan of Zhejiang provincial major science and technology (2023C03G1363376), Zhejiang Province health major science and technology plan project (WKJ-ZJ-2401), key project of Zhejiang Province Administration of Traditional Chinese Medicine (GZY-ZJ-KJ-24054).

Competing interests

The authors declare no conflict of interest.

Author Contribution

Jun Chen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Jun Chen, Liang He. Acquisition of data: Liang He, Xing Wang, Junfeng Yan. Analysis and interpretation of data: Yixiu Ni, Feijun Yu, Aokang Zhang. Drafting of the manuscript: Liang He, Yixiu Ni. Critical revision of the manuscript for important intellectual content: Jun Chen, Liang He. Statistical analysis: Liang He, Xing Wang, Junfeng Yan. Obtaining funding: Jun Chen. Administrative, technical, or material support: Liang He. Supervision: Jun Chen.

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No competing interests reported.

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You are reading this latest preprint version

Prevalence and associated risk factors of prostate cancer among a large Chinese population

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Journal Publication

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Abstract

Figures

Introduction

Methods

Population

Data Collection

Measures

Quality control

Ethics

Statistical Analysis

Results

Baseline information

Prevalence of of prostate cancer by subgroups

Associated risk factors of prostate cancer

Discussion

Conclusion

Declarations

Author Contribution

References

Additional Declarations

Status:

Journal Publication

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