Nutrition 106 (2023) 111868

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Nutrition
journal homepage: www.nutritionjrnl.com

Applied nutritional investigation

Fatty foods and the risk of bladder cancer: A case-control study

Chunying Teng Ph.D. a,b, Sicong Zheng M.D. b, Wenting Wan M.D. b, Lihua Liu Ph.D. b,
Siwen Yu M.D. c, Muyang Cao M.D. c, Weihong Lu Ph.D. a,*, Yujuan Shan Ph.D. b,*
a
Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, China
b
School of Public Health and Management, Wenzhou Medical University, Wenzhou, China
c
Department of Urology, Harbin Medical University Cancer Hospital, Harbin, China

A R T I C L E I N F O A B S T R A C T

Article History: Objective: The aim of this study was to explore the association between dietary fatty foods and the risk for
Received 10 October 2021 bladder cancer.
Received in revised form 21 September 2022 Methods: Patients newly diagnosed with bladder cancer (n = 113) and 292 controls were recruited. A food fre-
Accepted 6 October 2022
quency questionnaire (FFQ) was used to investigate the food intake within 1 y. Multivariate logistic regres-
sion model was used to estimated odds ratio (OR) between different types of fatty food consumption and
Keywords:
bladder cancer.
Fatty food
Results: The consumption of soybean oil, the largest proportion of cooking oil, in both groups were much
Bladder cancer
Case
control study
higher than the Chinese recommended dietary intake, especially in the control group. Higher intake of red
meat was also observed in bladder cancer cases, although lower intakes of marine fish, egg, milk, and dairy
products and nuts were observed in controls. After adjusting for potential confounders, the intakes of marine
fish and milk and dairy products were negatively correlated with bladder cancer, with the adjusted OR of
0.28 (95% confidence interval [CI], 0.15
0.55) and 0.36 (95% CI, 0.19
0.69). Total nuts were related to a 76%
reduction in bladder cancer risk (OR, 0.24; 95% CI, 0.12
0.48). There was clear and positive association
between soybean oil and bladder cancer risk with OR of 3.47 (95 % CI, 1.69
7.14). In stratified analyses by
sex and smoking status, the relationship was similar for most results, except for milk and dairy products. The
negative correlation between milk and dairy products and bladder cancer risk was only found in men; and
milk and dairy products and bladder cancer risk were irrelevant by smoking status. No significant association
was found between the intakes of other foods and bladder cancer risk.
Conclusions: Intake of nuts and marine fish may be beneficial for the prevention of bladder cancer. The pro-
tective effect of milk and dairy products was only found in men with bladder cancer. High soybean oil intake
was a risk factor for bladder cancer.
© 2022 Elsevier Inc. All rights reserved.

Introduction [3]. Approximately 70% to 75 % of all bladder malignancies are

Bladder cancer is a malignant tumor of the urinary system. It
has a high incidence rate and easily leads to relapse. On a global
scale, bladder cancer ranked as ninth among the most common
cancers and 13th on the incidence spectrum of malignant tumors
in China [1,2]. Incidence in developed countries has increased each
year. However, mortality rates were greater in developing regions
WL and YS conceptualized, supervised and wrote, reviewed, and edited the study.
CT wrote, reviewed, and edited the study and was responsible for the study meth-
odology and investigation. SZ and WW were involved in the formal analysis and
investigation. LL was responsible for the data curation and validation. SY and MC
were responsible for the resources and data curation. The authors have no conflicts
of interest to declare.
*Corresponding authors: Tel.: +88 45870641; Fax: 86-577-888991376.
E-mail addresses: lwh@hit.edu.cn (W. Lu), yujuanshan@wmu.edu.cn (Y. Shan).
diagnosed in superficial tumor stages [4], characterized by a high
recurrence rate and a relatively low progression rate [5]. As a
result, lifelong surveillance regimens are necessary to detect recur-
rences at the earliest possible stage. Bladder cancer is known as
the most expensive cancer for these reasons [6]. Nearly 80% of
bladder cancer can be attributed to lifestyle and diet [7]. The
known risk factors for bladder cancer include smoking, sex, occu-
pational exposure, chemical exposure both in diets and water, and
extent of obesity [8
10]. Harmful ingredient carcinogens in diets
or drinking water is excreted through the urinary tract and directly
contacted with the bladder epithelium [11], initiating the occur-
rence of bladder cancer. Previous epidemiologic studies about the
influence of diet intake on risk for bladder cancer have yielded
inconsistent results. A few vegetables and fruits may be negatively

https://doi.org/10.1016/j.nut.2022.111868
0899-9007/© 2022 Elsevier Inc. All rights reserved.
2 C. Teng et al. / Nutrition 106 (2023) 111868
correlated with the risk for bladder cancer, particularly, cruciferous
vegetables and citrus fruits [12]. However, meat consumption,
especially meats for stewing or roasting, increased bladder cancer
risk [13]. Dietary fat may increase the risk for bladder cancer, but
the results varied. For instance, dietary fat or type of fat intake
were reported to be and positively related with multiple cancers
including bladder cancer [14]. Other meta-analysis [15,16] and sys-
tematic reviews [17] showed the positive effect of high intake of
dietary fat on the risk for bladder cancer. A case
control study
(200 cases and 386 controls) in Belgian on bladder cancer reported
an inverse association between olive oil intake and bladder cancer.
However, no potential associations were detected for any other
source or type of dietary fat [18].
Harbin is in the northeast of China, with nearly 6-mo winterlike
weather. Therefore, the diet of the residents is mainly rich in oil,
salt and barbecue, and the intake of fresh vegetables and milk is
insufficient, especially for the urban population. The present ran-
domized case
control trial aims to explore whether these dietary
habits may intrinsically relate to the pathogenesis of bladder can-
cer. The findings presented here might provide local dietary guid-
ance for prevention of bladder cancer.
Methods and materials
Study participants
This case
control study was conducted between October 2018 and December
2019. The participants of the study were patients with newly histologically con-
firmed bladder cancer at Harbin Medical University, Harbin, China. All cases were
interviewed within 1 wk of their diagnosis. To be eligible for this study, the
patients with bladder cancer were Han nationality and ages 25 to 80 y without
previous chemo- and radiotherapy. Patients were excluded if they had a history of
any cancer or other debilitating diseases. In all, 130 patients with bladder cancer
who met the eligibility criteria were identified and 113 were interviewed, yielding
a participation rate of 87%. Nine patients did not finish the interview because of
physical reasons and the remaining eight were previously diagnosed with cancer.
We conducted a 1:3 matched case
control study. Individuals (n = 292) who
matched by age (§ 5 y) to the cases were included as controls. The control group
was recruited from residents in the community through community advertise-
ments, flyers, written invitations, or referrals. The eligibility criteria for controls to
be enrolled in the study were to be free of previous or current cancer, urogenital
cancer, liver failure, heart failure, chronic bronchitis, chronic nephritis, hyperthy-
roidism, and aplastic anemia. We recruited 310 controls, of whom 18 (6%) who
were invited to participate in the study refused to be interviewed or were missing
dietary data and excluded. All participants had clear awareness and expressive
ability. With full understanding of the trial protocol and purpose, all participants
involved in the experiments provided written informed consent at enrollment.
The study protocol was carried out in accordance with the principles of the Hel-
sinki declaration and approved by the ethic committee of Harbin Medical Univer-
sity. This study was registered at clinicaltrials.gov.
Data collection
Qualified participants were invited to participate in the study. Individual infor-
mation was collected using a structured questionnaire. The investigators received
unified professional training in advance and obtained the relevant knowledge for
all participants relating to the 12 mo (1 y, including spring, summer, autumn, and
winter) before the study. Each interviewer completed the same number of inter-
views with cases and controls. The investigators only explained the meaning of
the relevant items of the scheme for the patients, to avoid inducing their answers
and any bias. Under the guidance of the researcher, all participants participated in
a 30-min face-to-face interview for collection of sociodemographic data, lifestyle
habits, and dietary intake. Lifestyle habits included smoking and alcohol consump-
tion. Smoking was classified as current, non-smokers, and ever-smokers. A current
smoker was defined as someone smoking at least 1 cigarette/d for >6 mo consec-
utively. Alcohol consumption was classified as current, never, and ever drinker. A
current drinker was defined as someone who drank alcohol >1 time/wk in the
past year. Height and weight were self-reported. Body mass index (BMI; kg/m2)
was calculated by dividing weight (kg) by height squared (m2)
Diet and lifestyle questionnaires
A food frequency questionnaires (FFQ) was designed and referenced to the
dietary guidelines for Chinese residents and modified according to the pre-
laboratory research questionnaire [19,20]. An FFQ with good reliability and valid-
ity was used to assess the participants’ daily consumption of various foods [21]. To
reduce the effects of dietary changes in patients with bladder cancer, the FFQ was
collected within 2 d after admission. Detailed information was collected on fre-
quency of consumption and portion size during the 12 mo before bladder cancer
diagnosis for cases and interview for controls. The FFQ consisted of two parts; one
was the basic situation with a nondietary questionnaire including age, sex, height,
weight, education, occupation, and consumption of tobacco and alcoholic. The
other was the average frequency of consumption of 59 food items belonging to 10
categories over the previous year. The categories were vegetables, fruits, bacteria
and algae, grains and products, potatoes, eggs, milk and dairy products, soybeans
and products, nuts, poultry red meat (included pork, beef, and mutton), freshwater
fish, and marine fish. For each individual food item, average frequency and quan-
tity were recorded. According to the actual situation, food consumption was
divided into seven levels (50, 50
100, 100
150, 150
200, 200
250, 250
300,
and 300 g). Frequency of food intake was collected based on a fixed response for-
mat with seven categories (never/seldom, 1
3 £ /mo, 1 £ /wk, 2
3 £ /wk, 4
5 £ /
wk, daily, 2 £ /d).
With respect to the assessment of quantity of food intake, we used a retro-
spective diet-assisted survey with reference to food maps [22]. Food photographs
and reference size were used to help participants accurately quantify their dietary
intakes. Estimated daily fat intakes were calculated by multiplying the weight of
each food of the specific portion size by the frequency of consumption as stated on
the FFQ. The original data of the dietary questionnaire were entered by Epidata3.0
software, and the nutrient contents of each food item to calculate using Fei-Hua
Nutrition Calculator software.
All questionnaire information was recorded and entered by two individuals,
and the information was checked regularly.
Quality control
Reliability and validity of the FFQ were tested [20,23]. The correlation between
annual FFQ and 24-h dietary recall was analyzed to test the validity of FFQ. Also,
the quality of the questionnaires were controlled in a variety of ways. During the
investigation, the Dietary Food Estimation Tool Atlas, which has been publicly rec-
ognized in China, was widely applied to assist in determining quantities of food
intake. Participants could accurately quantify their dietary intake by looking at
food photos. To minimize memory bias in older adults, we allowed family mem-
bers to assist with the FFQ survey. Epidata3.0 was used to establish a special data-
base to enter the basic population data. All questionnaires were input by the two-
person simultaneous entry method and confirmed after careful checking. The two
input results were compared, and the entered information could be confirmed
only after no difference existed.
Statistical analysis
For continuous variables, Normal data distribution was verified using a Shapir-
o
Wilk test check to conform to the normal distribution. Differences between
cases and controls were assessed using the t test, which was used for continuous
variables conforming to normal distribution. The Wilcoxon signed-ranks test was
used for continuous variables that did not conform to normal distribution and
expressed using median and interquartile spacing. The x2 test was used for the
categorical variables to compare the difference between cases and controls for cat-
egorical demographic variables. Fatty foods and types of fatty food were analyzed
by Wilcoxon signed-ranks test to compare the differences between cases and the
controls.
To assess the association between total fatty foods and types of fatty food
intake and risk for bladder cancer, the conditional logistic regression model (odd
ratios [ORs]) and 95% confidence intervals (CIs) corresponding to the remaining
intervals for bladder cancer associated with total fatty foods and types of fatty
food intake per quartile were used. Age and BMI were regarded as continuous vari-
ables. The following potential confounding factors were included in the model
based on comparison of characteristics between cases and controls, or previous
report: sex (man, woman), educational level (high school and above, senior high
school and above), occupation (unemployed, peasant, worker, and officer), smok-
ing status (current, non-smokers and ever-smokers), alcohol drinking (as current,
never, and ever-drinker). All confounders were included as categorical variables.
The data were analyzed as quartiles (Q1
Q4). The cutoff points were based on the
intake of all participants. The lowest quartile (Q1) served as the reference group.
Tests for trend were performed across categories of exposure by ordinal categori-
cal all kinds of food as the continuous categorical variables (Q1
Q4) in the regres-
sion models.
Tests for linear trend were carried out by entering the categorical variable as
continuous variable in the regression model. Considering the significant associa-
tion of sex with the risk for bladder cancer [10], we further estimated model
parameters using unconditional logistic regression models in sex-stratification
analysis to assess the association of total fatty foods and types of fatty food intake
and risk for bladder cancer. All statistical tests were two-sided, and P < 0.05 was
 C. Teng et al. / Nutrition 106 (2023) 111868 3

Table 1 group. For both men and women, intake of marine fish, milk and
Sociodemographic information of participants dairy products, and nuts were lower, and on the contrary, soybean
Variable Cases (n = 113) Controls (n = 292) oil was much higher than that in the control. Additionally, for
women, the intake of egg and soybeans products in the case group
Age (y) 63.1 § 10.52 62.6 § 12.33
BMI (kg/m2) 23.7 § 2.72 24.2 § 2.90 were less than those in controls.
Sex, n (%) Overall, associations between different sources of fatty foods and
Men 78 (69) 155 (53.1) risk for bladder cancer were only marginally affected by adjustment.
Women 35 (31) 137 (46.9) The only exception was the disappearance of the inverse association
Degree of education, n (%)
Below high school 77 (68.1) 128 (43.8)
with freshwater fish and the positive association with red meat in
Senior high school and above 36 (31.9) 164 (56.2) multivariate analyses (Table 4). The intake (Q4 versus Q1) of marine
Occupation, n (%) fish, milk and dairy products, and nuts was inversely associated
Unemployed 18 (15.9) 23 (7.9) with risk for bladder cancer (for marine fish: adjusted OR [aOR],
Peasant 36 (31.9) 13 (4.5)
0.28; 95% CI, 0.15
0.55; Ptrend < 0.0001; milk and dairy products:
Worker 28 (24.8) 111 (38)
Officer 31 (27.4) 145 (49.7) aOR, 0.36; 95% CI, 0.19
0.69; Ptrend < 0.0001, and nuts: aOR, 0.24;
Consumption of tobacco, n (%) 95% CI, 0.12
0.48; trend < 0.0001). In contrast, significant positive
Current 55 (48.7) 53 (18.2) relationships were observed between the risk for bladder cancer
Never or ever 58 (51.3) 239 (81.8) and soybean oils in Q4 versus Q1 (OR 3.47; 95% CI 1.69
7.14; Ptrend
Consumption of alcohol, n (%)
Current 45 (39.8) 76 (26)
< 0.0001). No statistical association was observed between other
Never or ever 68 (60.2) 216 (74) foods intake and risk for bladder cancer.
BMI, body mass index
As shown in Table 5, risk for bladder cancer was negatively
Continuous variables represented by mean § SD and analyzed by t test. Classified associated with consumption of milk and dairy products in
variables represented by number (%) and analyzed by x2 test patients of both sexes. After adjustment for various confounders,
the negative correlation between milk and dairy products and risk
considered statistically significant. Statistical analyses were done using the SPSS
for bladder cancer was only found in men. An inverse association
version 23 (IBM, Armonk, NY, USA). was observed between consumption of marine fish or nuts and
bladder cancer with OR value in Q4 versus Q1 (OR, 0.30; 95% CI,
0.14
0.65; Ptrend < 0.0001; OR, 0.25; 95% CI, 0.10
0.60; Ptrend <
Results
0.0001; OR, 0.25; 95% CI, 0.066
0.94; Ptrend = 0.01 in men; and OR,
0.23; 95% CI, 0.067
0.79; Ptrend = 0.011 in women, respectively).
The demographic characteristics of study participants are pre-
Soybean oil was significantly positive correlation with bladder can-
sented in Table 1. There was no difference in age or BMI among
cer among all participants, with OR, 6.20; 95% CI, 2.53
15.18; P
the study population. Obvious differences were observed in educa-
trend < 0.0001 in men and OR, 1.60; 95% CI, 0.93
2.68; Ptrend = 0.029
tion, occupation, smoking, and alcohol consumption between the
in women in Q4 versus Q1.
two groups. The proportion of smoking and alcohol consumption
Smoking status stratified analyses showed similar results (Sup-
in the case group was significantly higher than in the controls.
plementary Table 1). Higher intake of marine fish or nut was asso-
As shown in Table 2, both total foods rich in fat (fatty foods)
ciated with lower risk for bladder cancer, and higher intake of
and animal-derived fatty foods were significantly lower in the
soybean oil products was positively linked with risk for bladder
cases than in the control group; however, red meat and soybean
cancer. However, there was no relationship between the intake of
oil consumption in cases were higher than that of the control. It
milk and dairy products and risk for bladder cancer.
should be mentioned that cases ate fewer marine fish and milk
and dairy products, as well as eggs and nuts than did controls.
In light of the different incidences of bladder cancer and possi- Discussion
ble relationship with food preferences between men and women,
we further analyzed the data according to the participants’ sex In this study, we focused on the relationship between different
(Table 3). All cases consumed less animal-derived fat foods, marine fatty foods and the risk for bladder cancer in a randomized case

fish, milk and dairy products, and nuts compared with the control control trial. The findings indicated that the consumption of

Table 2
Quantities of foods rich in fats in the participants

Variable (g/d) Cases (n = 113) Controls (n = 292) P value*

Mean Median P25, P75 Mean Median P25, P75

Total fatty foodsy 258.7 235 155, 325.8 312.9 295.8 183.3, 407.5 0.001
Animal-derived foods 171.7 141.7 75, 243.3 221.2 200 105, 313.3 <0.0001
Red meat 53.2 50 25, 66.7 42.6 35 16.7, 60 0.014
Poultry 12.2 8 3.3, 15.8 8.4 5 3.3, 10 0.074
Freshwater fish 7.1 5 3.3, 10 10.3 5 3.3, 10 0.106
Marine fish 5.1 0 0, 5 10.3 6.7 0, 11.7 <0.0001
Egg 30.5 16.7 13.3, 50 35.3 50.0 16.7, 50 0.001
Milk and dairy products 65.6 15 0, 90 114.3 77.5 13.3, 192.5 <0.0001
Plant-derived foods 86.9 75 61.7, 103.3 91.7 80 60.3, 111.7 0.43
Soybean products 25.6 16.7 7.5, 41.7 30.5 21.7 10, 41.7 0.12
Nuts 9.3 3.3 0, 100 170 6.7 0.75, 22.5 <0.0001
Soybean oil 46.2 50 41.7, 56.7 37.3 37.5 25, 50 <0.0001
*P analyzed by Wilcoxon rank-sum test using the median.
y
Total fatty foods included animal-derived foods (red meat, poultry, freshwater fish, marine fish, eggs, milk and dairy products) and plant-derived foods (soybeans and soy
products and nuts).
4 C. Teng et al. / Nutrition 106 (2023) 111868

Table 3
Intake of different types of fat foods in participants (by sex)*

Variable (g/d) Men (n = 233) Women (n = 172)

y
Cases (n = 78) Controls (n = 155) P value Cases (n = 35) Controls (n = 137) P valuey

Mean Median P25, P75 Mean Median P25, P75 Mean Median P25, P75 Mean Median P25, P75

Total fatty foods 264 245.8 164.2, 328.3 307.3 283.3 175,400 056 246.7 218.3 141.7, 326.7 319.2 300 193.3, 411.7 0.007
Animal-derived foods 175.4 145 75, 238.8 216.6 193.3 100,301.7 029 163.6 126.7 70, 256.7 226.3 205 108.3, 319.2 0.008
Red meat 55.9 48.3 26.3, 70.8 47.5 40 20,66.7 0.22 47 50 20, 61.7 37.2 30 16.7, 51.7 0.062
Poultry 13.1 10 3.3,16.7 9.2 5 5, 10 0.10 10.1 5 0, 15 7.5 5 3.3,10 0.80
Freshwater fish 10.3 5 3.3, 10 11.9 5 0, 10 0.47 5.6 5 3.3, 6.7 11.1 5 3.3, 10 0.095
Marine fish 6.2 0 0, 5 11.6 8.3 0, 13.3 0.001 2.7 0 0, 5 8.7 5 0, 10.8 <0.0001
Egg 31.3 16.7 13.3, 50 33.3 30 13.3, 50 0.11 29 16.7 6.7, 50 37.5 50 16.7, 50 0.006
Milk and dairy products 62.9 12.5 0,77.5 105.5 65 10, 158.3 <0.0001 71.7 33.3 0, 150 124.3 108.3 14.2, 222.5 0.008
Plant-derived foods 88.7 80 64.6, 101.7 90.7 80 60, 105.8 0.83 83 66.7 53.3, 115 92.9 80 60.8, 118.3 0.081
Soybeans and products 35.1 24.2 8.3, 41.7 39.9 23.3 10, 41.7 0.87 20.8 10 5, 23.3 32.1 21.7 10, 41.7 0.013
Nuts 9.9 3.3 0, 10 16.5 8 0, 16.7 <0.0001 7.8 3.3 0, 10 17.5 6.7 1.7, 25 0.003
Soybean oil 48.2 50 42.9, 56.7 38.9 40 26.7, 53.3 <0.0001 41.7 50 30, 53.3 35.3 33.3 25, 46.7 0.019
*Data represented by median (P25, P75).
y
P analyzed by Wilcoxon rank-sum test using the median.

marine fish, milk and dairy products, and nuts were protective fac-
tors for bladder cancer, whereas consumption of soybean oil was a
risk factor for bladder cancer. In stratified analyses by sex, the rela-
tionship was similar for most results. Apart from milk and dairy
products, the negative correlation between these products and the
risk for bladder cancer was only found in men. To our knowledge,
no such clinical trial has been carried out in northeast China, which
owns their specific eating habits.
Some studies have evaluated the consumption of marine fish
and the risk for bladder cancer, but the results are inconsistent

Table 4
Different types and amounts of fatty food and the risk of bladder cancer

Variable Q1 Q2 Q3 Q4 P value

OR (95% CI) OR (95% CI) OR (95% CI)

Red meat (g/d) 0 » 20 20.1 » 36.7 36.8 » 60.8 60.9 » 285

Case/Control, n 21/87 27/73 30/66 35/66 0.082*
Crude 1 1.53 (0.80
2.93) 1.88 (0.99
3.58) 2.20 (1.17
4.12) 0.011 y
Adjust 1 1.47 (0.79
2.90) 1.49 (0.76
2.93) 1.64 (0.84
3.20) 0.17y
Poultry (g/d) 0.0 » 3.3 3.4 » 5.0 5.1 » 11.7 11.8 » 75
Case/Control, n 33/83 17/72 28/83 35/54 0.022*
Crude 1 0.59(0.31
1.16) 0.85 (0.47
1.53) 1.61 (0.91
2.93) 0.10y
Adjust 1 0.49 (0.24
0.99) 0.74(0.40
1.37) 1.30 (0.70
2.42) 0.34y
Freshwater fish (g/d) 0 » 3.3 3.4 » 5 5.1 » 10 10.1 » 105
Case/Control, n 32/88 37/62 33/75 11/67 0.007*
Crude 1 1.64 (0.92
2.91) 1.21 (0.68
2.15) 0.45 (0.21
0.96) 0.084 y
Adjust 1 1.70 (0.93
3.11) 1.18 (0.64
2.16) 0.48 (0.22
1.06) 0.12y
Marine fish (g/d) 0.0 » 0.0 0.1 » 5.0 5.1 » 10.0 10.1 » 116.7
Case/Control, n 76/98 12/45 10/73 16/75 <0.0001*
Crude 1 0.34 (0.17
0.70) 0.18 (0.085
0.37) 0.26 (0.14
0.48) <0.0001 y
Adjust 1 0.43 (0.21
0.89) 0.19 (0.088
0.40) 0.28 (0.15
0.55) <0.0001 y
Egg (g/d) 0 » 16.7 16.8 » 33.3 33.4 » 50 50.1 » 150
Case/Control, n 62/110 13/27 28/138 10/16 0.001*
Crude 1 0.85 (0.41
1.78) 0.36 (0.22
0.60) 1.11 (0.47
2.59) 0.004y
Adjust 1 0.74 (0.34
1.60) 0.36 (0.21
0.60) 0.98 (0.40
2.43) 0.004 y
Milk and dairy products (g/d) 0»0 0.1 » 75 75.1 » 158.3 158.4 » 475
Case/Control, n 52/65 30/81 12/65 81/19 <0.0001*
Crude 1 0.46 (0.27
0.81) 0.23 (0.11
0.47) 0.29 (0.16
0.54) <0.0001 y
Adjust 1 0.54 (0.30
0.96) 0.29 (0.14,0.61) 0.36 (0.19
0.69) <0.0001y
Soybeans and products (g/d) 0 » 10 10.1 » 21.7 21.8 » 41.7 41.8 » 181.7
Case/Control, n 45/91 17/56 28/85 23/60 0.37*
Crude 1 0.61 (0.32
1.18) 0.67 (0.38
1.16) 0.78 (0.43
1.41) 0.29y
Adjust 1 0.69 (0.35
1.36) 0.60 (0.33
1.08) 0.75 (0.40
1.41) 0.21y
Nut (g/d) 0»0 0.1 » 5 5.1 » 16.7 16.8 » 150
Case/Control, n 54/73 22/60 23/85 14/74 <0.0001*
Crude 1 0.50 (0.27
0.91) 0.37 (0.21
0.65) 0.26 (0.13
0.50) <0.0001y
Adjust 1 0.48 (0.25
0.90) 0.33 (0.18
0.61) 0.24 (0.12
0.48) <0.0001y
Soybean oil (g/d) 0 » 29.1 29.2 » 41.7 41.8 » 53.3 53.4 » 90
Case/Control, n 14/87 20/103 39/44 40/58 <0.0001*
Crude 1 1.21 (0.58
2.53) 5.51 (2.71
11.21) 4.29 (2.14
8.57) <0.0001y
Adjust 1 1.26 (0.59
2.68) 4.42 (2.12
9.23) 3.47 (1.69
7.14) <0.0001y
CI, confidence interval; OR, odds ratio.
Crude: not adjusted; Adjust: adjusted for smoking, alcohol drinking, sex, degree of education, occupation
*Significance test of the quartered value.
y
Significance test of risk factors.
Table 5
Bladder cancer according to quartiles of the intake of different types and amounts of fatty food by sex

Men (n = 233) Ptrend Women (n = 172) Ptrend

Variable Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4

OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI)

Red meat (g/d) 0 » 25 25.1 » 41.7 41.8 » 66.7 66.8 » 285 0.0 » 16.7 16.8 » 33.3 33.4 » 54.6 54.7 » 250
Case/Control, n 19/48 15/36 24/35 20/36 0.45* 6/40 8/36 11/28 10/33 0.34*
Crude 1 1.05 (0.47
2.35) 1.73 (0.82
3.64) 1.4 (0.66
3.01) 0.22 b 1 1.48 (0.47
4.68) 2.62 (0.87
7.91) 2.02 (0.66
6.14) 0.14y
Adjust 1 0.97 (0.42
2.23) 1.55 (0.72
3.34) 1.08 (0.49
2.41) 0.58y 1 1.80 (0.54
6.02) 2.51 (0.77
8.16) 1.79 (0.53
6.05) 0.29y
Poultry (g/d) 0 » 4.2 4.3 » 6.7 6.8 » 15 15.1 » 75 0 » 3.3 3.4 » 5 5.1 » 10 10.1 » 75
Case/Control, n 20/38 14/45 23/44 21/28 0.21* 13/45 5/28 7/40 10/24 0.35*
Crude 1 0.59 (0.26
1.33) 0.99 (0.47
2.08) 1.43 (0.65
3.12) 0.24y 1 0.62 (0.20
1.92) 0.61 (0.22,
1.67) 1.44 (0.55
3.77) 0.71y
Adjust 1 0.54 (0.23
1.25) 0.92 (0.42
1.98) 1.21 (0.53
2.73) 0.44y 1 0.43 (0.12
1.52) 0.46 (0.16
1.38) 1.19 (0.43
3.33) 0.94y
Freshwater fish (g/d) 0 » 3.3 3.4 » 5 5.1 » 10 10.1 » 75 0 » 3.3 3.4 » 5 5.1 » 10 10.1 » 105
Case/Control, n 21/51 26/30 22/37 9/37 0.027* 11/38 11/31 11/38 2/30 0.17*
Crude 1 2.11 (1.01
4.37) 1.44 (0.69
3.00) 0.59 (0.24
1.44) 0.35y 1 1.23 (0.47
3.21) 1.00 (0.39
2.58) 0.23 (0.47
1.12) 0.12y
Adjust 1 2.07 (0.97
4.42) 1.34 (0.62
2.87) 0.60 (0.24
1.49) 0.34y 1 1.39 (0.50
3.87) 1.01 (0.37
2.79) 0.33 (0.66
1.69) 0.26y
Marine fish (g/d) 0»0 0.1 » 5 5.1 » 10 10.1 » 116.7 0»0 0.1 » 5 5.1 » 10 10.1 » 91.7
Case/Control, n 53/50 7/20 6/43 12/42 <0.0001* 24/49 5/25 3/30 3/33 0.004*
Crude 1 0.33 (0.13
0.85) 0.13 (0.052
0.34) 0.27 (0.13
0.57) <0.0001y 1 0.41 (0.14
1.20) 0.20 (0.06
0.74) 0.19 (0.05
0.67) 0.001y

C. Teng et al. / Nutrition 106 (2023) 111868

Adjust 1 0.38 (0.14
1.00) 0.14 (0.06
0.38) 0.30 (0.14
0.65) <0.0001y 1 0.61 (0.20
1.92) 0.24 (0.064
0.93) 0.25 (0.07
0.94) 0.01y
Eggs (g/d) 0 » 13.3 13.4 » 30 30.1 » 50 50.1 » 150 0.0 » 16.7 16.8 » 33.3 33.4 » 50 50.1 » 150
Case/Control, n 22/39 23/40 26/65 7/11 0.645* 20/42 3/13 9/77 3/5 0.007* \
Crude 1 1.02 (0.49
2.12) 0.71 (0.36
1.42) 1.13 (0.38
3.33) 0.55y 1 0.49 (0.12
4.90) 0.25 (0.10
0.59) 1.26 (0.27
5.80) 0.014y
Adjust 1 0.83 (0.38
1.80) 0.60 (0.29
1.24) 1.00 (0.33
3.10) 0.38y 1 0.52 (0.12
2.22) 0.22 (0.084
0.56) 0.94 (0.17
5.09) 0.009y
Milk and dairy products (g/d) 0»0 0.1 » 50 50.1 » 130 130.1 » 475 0 » 10. 10.1 » 85 85.1 » 192.5 192.6 » 475
Case/Control, n 38/37 14/36 13/37 13/45 0.002* 15/31 9/31 5/38 6/37 0.058*
Crude 1 0.38 (0.18
0.81) 0.34 (0.16
0.74) 0.28 (0.13
0.61) 0.001y 1 0.60 (0.23
1.57) 0.27 (0.089
0.83) 0.34 (0.12
0.97) 0.011y
Adjust 1 0.45 (0.20
0.99) 0.40 (0.18
0.89) 0.34 (0.15
0.74) 0.004y 1 0.56 (0.20
1.58) 0.31 (0.10
1.00) 0.36 (0.13
1.09) 0.033y
Soybeans and products (g/d) 0 » 10 10.1 » 23.3 23.4 » 41.7 41.8 » 180 0.» 10 10.1 » 20 20.1 » 41.7 41.8 » 181.7
Case/Control, n 25/54 14/27 22/45 17/29 0.94* 20/37 4/29 5/39 6/32 0.008*
Crude 1 1.12 (0.50
2.50) 1.06 (0.53
2.12) 1.27 (0.59
2.72) 0.61y 1 0.26 (0.079
0.83) 0.24 (0.081
0.70) 0.35 (0.12
0.97) 0.019y
Adjust 1 1.18 (0.51
2.73) 0.95 (0.46
1.96) 1.23 (0.55
2.71) 0.77y 1 0.31 (0.093
1.06) 0.25 (0.081
0.78) 0.33 (0.11
1.01) 0.029y
Nuts (g/d) 0»0 0.1 » 5 5.1 » 16.7 16.8 » 150 0»0 0.1 » 5 5.1 » 16.7 16.8 » 125
Case/Control, n 37/39 15/30 16/50 10/36 0.004* 17/34 7/29 7/36 4/38 0.032*
Crude 1 0.53 (0.25
1.13) 0.34 (0.16
0.69) 0.29 (0.13
0.67) 0.001y 1 0.48 (0.18
1.33) 0.39 (0.14
1.05) 0.21 (0.06
0.69) 0.005y
Adjust 1 0.51 (0.23
1.14) 0.31 (0.15
0.66) 0.25 (0.10
0.60) <0.0001y 1 0.45 (0.15
1.31) 0.37 (0.13
1.07) 0.23 (0.07
0.79) 0.011y
Soybean oil (g/d) 0 » 33.3 33.4 » 43.3 43.4 » 55 55.1 » 90 0 » 26.7 26.8 » 41.3 41.4 » 50 50.1 » 75
Case/Control, n 9/73 18/20 25/33 26/29 <0.0001* 5.41 8/32 10/42 12/22 0.064*
Crude 1 7.30 (2.85
18.70) 6.15 (2.59
14.61) 7.27 (3.04
17.9) <0.0001y 1 2.05 (0.61
6.87) 1.95 (0.61
6.21) 4.47 (1.4
14.34) 0.019y
Adjust 1 7.45 (2.85
19.49) 4.96 (2.03
12.12) 6.20 (2.53
15.18) <0.0001y 1 2.02 (0.56
7.28) 2.02 (0.60
6.83) 4.31 (1.25
14.88) 0.029y
CI, confidence interval; OR, odds ratio.
Crude: not adjusted; Adjust: adjust for smoking, alcohol drinking, degree of education, occupation
*Significance test of the quartered value.
y
Significance test of risk factors.

5
6 C. Teng et al. / Nutrition 106 (2023) 111868
[24
27]. In the present study, the obviously negative correlation
between marine fish and bladder cancer was observed, which was
similar to a handful of epidemiologic literatures [24,28,29]. Marine
fish is publicly recognized as an ideal source of v-3 polyunsatu-
rated fatty acids (v-3PUFAs) [30], which have been shown to
inhibit tumor growth and the expression of proinflammatory
genes [24]. However, a meta-analysis involving five cohort and
nine case
control studies did not showed any relationship
between fish intake and bladder cancer [27].
A meta-analysis of 26 cohort and prospective studies deter-
mined that the consumption of milk and dairy products may
reduce the risk for bladder cancer [31,32]. In agreement with
results, the present study found a significant inverse association of
milk and dairy product intake and the risk for bladder cancer rik
among men. Milk contains lignans and lactoferrin, which have
been shown to possess anticarcinogenic activity [33]. Additionally,
milk and dairy products also contain conjugated linoleic acid
(CLA), which exerts antineoplastic activity. At the same time, CLA
reduced bladder cancer cell proliferation and increased bladder
cancer cell apoptosis in vivo [34]. The current findings showed that
intake of nuts was negatively correlated with the occurrence of
bladder cancer, which has been reported in colorectal cancer [35],
lung cancer [36], and breast cancer [37].
Nuts contain more monounsaturated fatty acids and PUFAs,
such as oleic acid and a-linolenic acid, with the latter being an
important v-3PUFA [38]. Moreover, nuts contain many bioactive
compounds including polyphenols, ellagic acid, and phytoestro-
gens, which prevent tumor development and progression [39,40].
The components of nuts have been reported to inhibit the invasion
and growth in cultured bladder cancer cells [41].
We herein found that soybean oil is the most indispensable and
traditional cooking oil in participants with less consumption of
corn oil and olive oil. The mean intake in control was around 37.5
g, reaching the highest limit of the Chinese Dietary Guidelines
(25
30 g for oil per day) [19]. However, the average consumption
in bladder cancer patients was around 50 g, far beyond the Chi-
nese Dietary Guidelines. To our knowledge, 50% of the fatty acids
in soybean oil exist in the form of linoleic acid (LA) [42,43]. LA is
rich in v-6 PUFAs, which are metabolized to a variety of pro-
inflammatory factors such as prostaglandin 2, leukotriene B4,
thromboxane B2 [44]. LA promoted the growth of tumors in the
rodent tumor and human cancer xenografts in nude rats [45] due
to its metabolites. Meanwhile, chronic inflammation has been con-
firmed to elicit bladder carcinogenesis [46].
Studies have shown that being of male sex and smoking are risk
factors for bladder cancer [29,47,48]. Therefore, fewer women
were enrolled in our case group. To further avoid the influence of
sex and smoking confounding factors, we conducted a stratified
analysis of sex and smoking status. After analysis of sex stratifica-
tion, the results between men or women and the risk for bladder
cancer were almost the same as before. Only the risk for milk
intake and bladder cancer disappeared the women. It has been
suggested [48
50] that sex differences in risk for bladder cancer
risk may be attributed to the specific variation in bladder cancer-
related carcinogen metabolism affected by sex hormones. There-
fore, the mechanism of milk and dairy product intake on the risk
for bladder cancer in men and women requires further exploration.
When stratified by smoking status, the intake of milk and dairy
products was not associated with the occurrence of bladder cancer.
This was consistent with other findings [26,51]. Therefore, further
studies are required to demonstrate the potential interaction
between smoking and intake of milk and dairy products on the
risk for bladder cancer. Therefore, sex and smoking habits had less
residual confounding effects on the relationship between total
fatty food and fatty food intake types and bladder cancer.
Pressing questions
We used a validated semiquantitative FFQ to measure con-
sumption of different fatty foods during the past 12 mo. Like previ-
ous case
control studies, the present study has the possibility of
recall errors. Face-to-face interviews were conducted by trained
interviewers within hospital settings for cases and controls to limit
possible information bias. The use of retrospective dietary survey
and the reference Dietary Food Estimation Tool Atlas also helped
to guarantee the accuracy of data. Because of the sex variations in
bladder cancer incidence, only 35 women were enrolled. There-
fore, to reduce the effects of sex on the study results, we conducted
a stratified analysis of sex.
Conclusions
Fatty foods exhibited a very complex relationship with bladder
cancer. Excessive intake of soybean oil possibly contributed to
bladder carcinogenesis. Marine fish and nuts probably were a pro-
tective factor for all patients with bladder cancer. The protective
effects of milk and dairy products were only found in the men with
bladder cancer. Further studies are necessary to determine the pos-
sible effects of fatty foods composition on the risk for bladder can-
cer.
Acknowledgments
The authors acknowledge the study participants for their con-
tribution to this research. They also acknowledge Yongping Bao,
University of East Anglia, UK, for his critical review of manuscript.
The authors acknowledge the National Natural Science Foundation
of China (81773427) for the foundations’ support.
Supplementary materials
Supplementary material associated with this article can be
found in the online version at doi:10.1016/j.nut.2022.111868.
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