Walking Time, Sports Activity, Job Type, and Body Posture During Work in Relation to Incident Colorectal Cancer: The JACC Prospective Cohort Study

doi:10.21203/rs.3.rs-423828/v1

Purpose

An inverse association between physical activity and colorectal cancer (CRC) was suggested. We aimed to assess the specific and combined effects of leisure-time and occupational physical activities on CRC risk among Japanese adults.

Methods

Using Cox proportional hazard models, we tested whether walking time, sports activity, body posture during work, and job type– or the combination of these variables – were associated with CRC incidence during 17 years of follow-up (1990–2009) in a prospective cohort of 26,897 Japanese men and women aged 40–79 years.

Results

During the follow-up period, 423 incident cases of CRC (267 colon and 156 rectum cancer) were ascertained. Time spent walking showed a dose-response inverse relationship with CRC risk (p-trend = 0.053). Manual labor was associated with lower CRC risk when compared to office work; HR (95%CI) = 0.75 (0.57–0.98) for colorectal cancer and 0.69 (0.48–0.97) for colon cancer. Compared to sitting, moving during work tended to be inversely associated with rectal cancer risk, especially after censoring early incident cases within 3 years after baseline; HR (95% CI) = 0.63 (0.40–0.99). Combining leisure-time walking with job type suggested mutual and synergistic benefits (p-interaction < 0.05). Compared to office workers walking < 1h/d, non-office workers walking < 1h/d had a 39% lower risk, office workers walking ≥ 1h/d had a 52% lower risk, while non-office workers walking ≥ 1h/d had a 40% lower risk of developing colon cancer.

Conclusions

The time spent walking, job type and posture during work were independently and additively associated with reduced incident CRC risk among Japanese men and women.

Cancer Biology

Oncology

walking time

sports activity

job type

posture during work

colorectal cancer

Japan

In 2018, the International Agency for Research on Cancer ranked colorectal cancer (CRC) the most commonly diagnosed cancer and the second leading cause of cancer deaths worldwide [1, 2]. In Japan, with the spreading of Westernized lifestyles after World War II, CRC morbidity and mortality were on the rise until the 1990s [3]. However, due to the Japanese recommendation to begin CRC screening at the age of 40 – which is very early compared to the recommended screening age of 59 years in the USA or 50–74 years in Europe [2] – the CRC mortality trend in Japan showed a recent decline [4]. Nonetheless, 10% of Japanese men and 8% of Japanese women are likely to be diagnosed with CRC within their lifetimes [5].

Diet, obesity, and physical activity (PA) were suggested to be major modifiable CRC risk factors [2]. The published literature investigating the relationship between leisure-time [6–9] or occupational PA and CRC risk [9–11] reported a negative association between PA and colon cancer, but not rectal cancer. Several potential mechanisms were proposed to explain these associations, including local gastrointestinal effects, altered immune function, lowered serum cholesterol, and changes in insulin and insulin-like growth factor levels. [12].

Approximately 50% of East Asians are considered to be physically inactive [13] according to the World Health Organization’s recommended PA standard (moderate-intensity PA for 150 minutes or vigorous-intensity PA for 75 minutes weekly) [14], which is relatively high to initiate or maintain. Thus, in this study, we aim to investigate the specific and combined effects of leisure-time PA, posture during work, and job type on the risk of developing CRC among Japanese men and women participating in the Japan Collaborative Cohort (JACC) Study for Evaluation of Cancer Risk.

JACC study population

Between 1988–1990, 110,585 Japanese residents aged 40–79 years from 45 municipalities participated in a nationwide study to establish evidence-based preventive strategies against cancer. Details of the JACC study can be found in previous publications [15]. Data on cancer incidence, job type, and posture during work were unavailable in 21, two and four study areas, respectively. Among the remaining 56,146 respondents from 22 municipalities, we excluded 11,068 participants with a history of cancer at baseline, 4302 with missing data on leisure-time PA, and 13,879 with missing data on job type or posture during work. The final analytical sample consisted of 26,897 eligible participants. All respondents consented to participate in this study which was conducted in line with the Declaration of Helsinki and was approved by Osaka University and Hokkaido University’s ethical review boards.

Colorectal cancer

CRC incident cases were confirmed via population-based cancer registries, major hospital records, and/or death certificates. The follow-up period ended at the date of death, the date of moving out from the study area, or in December of the following years: 1994 in one study area, 1997 in two areas, 2000 in one area, 2003 in one area, 2006 in two areas, 2008 in three areas, and 2009 for the remaining 12 areas – whichever happened first. Thus, the mean and median follow-up periods were 14.8 and 17.9 years, respectively. The following International Statistical Classification of Diseases and Related Health Problems 10th Revision codes were used to define CRC: C18-C20 (C180 to C189 for colon cancer and C19 to C20 for rectal cancer).

Physical activity

In the JACC study, leisure-time PA was assessed with two questions: 1.) minutes spent walking per day and 2.) hours of sports activity per week. Possible answers on daily walking time were “almost none”, “less than 30 minutes”, “30 minutes to less than one hour”, or “one hour or more”, while responses on weekly sports activity were “almost none”, “one to two hours”, “three to four hours”, or “five hours or more”. The respondents were also asked to specify their job type – “manual work”, “office work”, or “other work” – and their occupational PA level, indicated by their body posture during work – “mainly sitting”, “mainly standing”, “sitting and standing”, or “moving”.

Covariates

The following variables were included in our models as potential confounders: age (continuous), sex (male, female), area of residence, family history of any cancer (yes, no), history of diabetes (yes, no), education (< 15, 16–18, ≥ 19 years), occupation (unemployed, part-time, fulltime, self-employed, housewife, other), TV watching (< 1.5, 1.5 to < 3, 3 to < 4.5, ≥ 4.5 hours per day), smoking habit (never, former, current smoker), alcohol consumption (never, former, current drinker of < 23, 23 to < 46, 46 to < 69, ≥69 grams of ethanol per day), body mass index calculated as weight in kilograms/squared height in meters (quintiles), stool habit (daily, once every 2–3 days, once every 4–5 days, once every week), as well as meat, vegetable, dietary fiber, folate, and total calorie intakes (quintiles).

Statistical analyses

Data were analyzed between January and June 2020. Participant characteristics were compared for CRC cases versus non-cases using independent sample t-tests and Chi-square tests. Three Cox proportional hazard regression models were constructed to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for developing CRC according to leisure-time PA levels (reference: “almost no” daily walking time / weekly sports activity), job type (reference: “office work”), and posture during work (reference: “mainly sitting”). The first model (Model 1) adjusted for age, sex, and area of residence; the second model (Model 2) further accounted for all covariates listed above; while the third model (Model 3) included mutual adjustments for all exposure variables as well. Sensitivity analyses were conducted after excluding respondents with CRC developed within the first three years of the follow-up period.

Two- and three-way interaction terms between the exposure variables were added to the models to test their potential additive or synergistic effects on the risk of CRC, colon cancer, and rectal cancer. Based on the results, further analyses were conducted after creating three new variables, combining 1.) walking time and job type, 2.) walking time and posture during work, and 3.) walking time, job type, and posture during work. SAS Software Version 9.4 (SAS Institute Inc., Cary, 131 NC, USA) was the used statistical tool, and two-sided p-values < 0.05 defined the level of statistical significance.

Compared to non-cases, the mean age of respondents who developed CRC during the follow-up period was higher at baseline (56.5 vs. 53.0 years). CRC cases were also more likely to be males (70.5% vs. 50.7%), current smokers (37.4% vs. 30.9%), office workers (19.5% vs. 15.7%), and to have higher daily ethanol (31.8 vs. 28.8 g/day) and total calorie intakes (1690.2 vs. 1596.4 kcal/day) (Table 1).

Table 1

Characteristics of colorectal cancer cases versus non-cases
	All participants of the study
	Colorectal cancer cases	Non-cases	P for difference ^a
Number of participants	423	26,474
Age, year	56.5 ± 8.2	53.0 ± 8.8	< 0.001
Male, %	70.5	50.7	< 0.001
History of hypertension, %	19.8	15.5	0.02
History of diabetes, %	4.9	3.4	0.09
Family history of CRC, %	4.3	2.8	0.06
Body mass index, kg/m²	22.7 ± 2.7	22.8 ± 2.8	0.67
Current smoker, %	37.4	30.9	< 0.001
TV viewing time, hour/day	2.5 ± 1.2	2.5 ± 1.3	0.92
Education > = 16 years, %	66.9	66.8	0.98
Daily stool habit, %	85.6	78.9	0.001
High perceived stress, %	58.4	59.6	0.35
Sports > = 3 hour/week, %	11.8	10.2	0.28
Walking > = 30 minutes/day, %	68.8	71.1	0.29
Job type Manual Office Other	43.0 19.6 37.4	48.7 15.7 36.6	0.03
Body posture during work Mostly sitting Sitting/standing Mostly standing Moving	36.6 7.1 16.6 39.7	35.9 6.3 17.2 40.6	0.87
Ethanol intake, g/day	31.8 ± 22.4	28.8 ± 22.9	0.05
Meat intake, g /day	30.1 ± 19.4	30.6 ± 20.3	0.64
Vegetable intake, g/day	295.9 ± 331.9	264.4 ± 316.1	0.05
Dietary fiber intake, g/day	10.8 ± 3.3	10.3 ± 3.3	0.01
Folate intake, mg/day	429.8 ± 164.2	416.6 ± 158.8	0.13
Energy intake, kcal /day	1690.2 ± 435.7	1596.4 ± 434.3	< 0.001

^a Independent sample t-test was used for continuous and Chi-square test for categorical variables.

Table 2 shows the associations between leisure-time physical activity and incident colorectal cancer risk. During 397,918 person-years of follow-up, 423 incident CRC cases were diagnosed (398 in men and 125 in women), including 267 cases of colon cancer (175 in men and 92 in women) and 156 cases of rectum cancer (123 in men and 33 in women). Daily time spent walking was inversely associated with the risk of CRC in a dose-response manner. Compared to respondents with almost no walking activity, the multivariable HRs (95% CIs) for CRC risk among participants walking < 30 min/d, 30 min/d to < 1h/d, and ≥ 1h/d were 0.92 (0.65–1.32), 0.78 (0.55–1.12), and 0.74 (0.54–1.02), respectively; p-trend 0.026 (Model 2). Further adjustment for sports activity, job type, and body posture during work attenuated the association; p-trend = 0.053 (Model 3). The decreasing CRC risk across longer daily walking time categories was observed for both colon and rectal cancers; however, these trends did not reach statistical significance. Higher sports activity was not significantly associated with CRC risk. Also, there were no significant interactions between sex and leisure-time physical activities; p-interaction > 0.1.

Table 2

Leisure-time physical activity and risk of incident colorectal cancer among Japanese men and women
	Walking					Sports
	Never	< 30 min/d	30–60 min/d	1 h or more/d	p-trend	Never	1–2 h/wk	3-4h/wk	5h or more/wk	p-trend
Participants, n	3022	4752	5331	13792		19677	4462	1508	1250
Person-year	42906	69614	78097	207301		291231	67027	21677	17982
Colorectal cancer, n	49	83	79	212		299	74	6831	19
Model 1	1.00	0.95 (0.67–1.36)	0.80 (0.56–1.15)	0.76 (0.55–1.04)	0.029	1.00	1.07 (0.82–1.38)	1.25 (0.86–1.81)	0.75 (0.47–1.20)	0.83
Model 2	1.00	0.92 (0.65–1.32)	0.78 (0.55–1.12)	0.74 (0.54–1.02)	0.026	1.00	1.03 (0.80–1.34)	1.22 (0.84–1.78)	0.73 (0.46–1.17)	0.66
Model 3	1.00	0.91 (0.64–1.30)	0.78 (0.54–1.12)	0.77 (0.56–1.05)	0.053	1.00	1.04 (0.80–1.35)	1.24 (0.85–1.81)	0.77 (0.48–1.23)	0.82
Colon cancer, n	31	47	54	135		188	50	16	13
Model 1	1.00	0.85 (0.54–1.34)	0.86 (0.55–1.33)	0.75 (0.50–1.11)	0.13	1.00	1.20 (0.88–1.65)	1.05 (0.63–1.76)	0.85 (0.48–1.50)	0.99
Model 2	1.00	0.81 (0.51–1.28)	0.83 (0.54–1.30)	0.74 (0.50–1.10)	0.17	1.00	1.14 (0.83–1.56)	1.03 (0.62–1.73)	0.84 (0.47–1.49)	0.86
Model 3	1.00	0.79 (0.50–1.26)	0.82 (0.52–1.29)	0.74 (0.50–1.11)	0.21	1.00	1.15 (0.83–1.59)	1.05 (0.62–1.76)	0.88 (0.49–1.56)	0.96
Rectal cancer, n	18	36	25	77		111	24	15	6
Model 1	1.00	1.13 (0.64–1.99)	0.70 (0.38–1.29)	0.78 (0.46–1.31)	0.11	1.00	0.86 (0.55–1.34)	1.56 (0.90–2.68)	0.60 (0.26–1.38)	0.73
Model 2	1.00	1.12 (0.63–1.97)	0.69 (0.38–1.28)	0.74 (0.44–1.24)	0.06	1.00	0.87 (0.55–1.36)	1.51 (0.88–2.62)	0.56 (0.25–1.30)	0.61
Model 3	1.00	1.12 (0.63–1.90)	0.71 (0.38–1.31)	0.80 (0.47–1.36)	0.16	1.00	0.86 (0.55–1.35)	1.53 (0.88–2.65)	0.60 (0.26–1.39)	0.71

Model 1: adjusted for age, sex, and area of residence.

Model 2: further adjusted for body mass index, history of diabetes, family history of cancer, education, occupation, stool habit, hours of watching TV, smoking habit, ethanol intake, and meat, vegetable, total dietary fiber, folate, and total energy intakes.

Model 3: further adjusted for job type, body posture during work, and mutually for walking/sports activity.

The results presented in Table 3 indicate that manual workers were at a lower risk of incident CRC and colon cancer than office workers; the multivariable HR (95% CI) in the fully adjusted model (Model 3) was 0.75 (0.57–0.98) for CRC and 0.69 (0.48–0.97) for colon cancer. The association between higher occupational PA – moving versus sitting during work – and CRC risk was in the same direction. However, it did not reach statistical significance; the multivariable HR (95% CI) was 0.86 (0.67–1.11) for CRC and 0.72 (0.47–1.10) for rectal cancer. After excluding CRC cases diagnosed during the first three years of the follow-up period, the findings did not change substantially (Online Resources 1 and 2).

Table 3

Job type and body posture during work and risk of incident colorectal cancer among Japanese men and women
	Job type			Body posture during work
	Office work	Manual work	Other work	Sitting	Standing	Sitting/standing	Moving
Participants, n	13079	4234	9584	9674	1686	4621	10916
Person-year	195025	65202	137691	148984	24414	66229	158292
Colorectal cancer, n	182	83	158	155	30	70	168
Model 1	1.00	0.70 (0.54–0.91)	0.77 (0.58–1.03)	1.00	1.00 (0.74–1.34)	1.13 (0.76–1.67)	0.83 (0.64–1.06)
Model 2	1.00	0.72 (0.55–0.95)	0.80 (0.60–1.07)	1.00	0.98 (0.73–1.32)	1.16 (0.78–1.72)	0.83 (0.65–1.06)
Model 3	1.00	0.75 (0.57–0.98)	0.83 (0.62–1.10)	1.00	0.99 (0.74–1.33)	1.15 (0.78–1.72)	0.86 (0.67–1.11)
Colon cancer, n	108	53	106	92	16	47	112
Model 1	1.00	0.63 (0.45–0.88)	0.75 (0.52–1.07)	1.00	1.07 (0.74–1.55)	1.00 (0.59–1.71)	0.89 (0.66–1.22)
Model 2	1.00	0.66 (0.47–0.94)	0.79 (0.55–1.14)	1.00	1.05 (0.73–1.52)	1.05 (0.61–1.78)	0.93 (0.68–1.27)
Model 3	1.00	0.69 (0.48–0.97)	0.82 (0.57–1.18)	1.00	1.06 (0.73–1.53)	1.05 (0.61–1.79)	0.96 (0.70–1.32)
Rectal cancer, n	74	30	52	63	14	23	56
Model 1	1.00	0.83 (0.54–1.28)	0.81 (0.50–1.30)	1.00	0.88 (0.54–1.44)	1.31 (0.73–2.34)	0.72 (0.48–1.08)
Model 2	1.00	0.82 (0.52–1.28)	0.80 (0.49–1.31)	1.00	0.89 (0.54–1.46)	1.32 (0.73–2.37)	0.69 (0.46–1.04)
Model 3	1.00	0.87 (0.55–1.39)	0.85 (0.52–1.39)	1.00	0.89 (0.54–1.47)	1.30 (0.72–2.34)	0.72 (0.47–1.10)

Model 1: adjusted for age, sex, and area of residence.

Model 2: further adjusted for body mass index, history of diabetes, family history of cancer, education, occupation, stool habit, hours of watching TV, smoking habit, ethanol intake, and meat, vegetable, total dietary fiber, folate, and total energy intakes.

Model 3: further adjusted for leisure-time physical activities, and mutually job type, and body posture during work.

For further comparison, all analyses were repeated with a reduced number of job type and body posture during work categories. Combining the “manual work” and “other work” groups, “non-office workers” showed lower CRC risk than “office workers”; the multivariable HR (95% CI) was 0.75 (0.58–0.97) for CRC and 0.72 (0.52–0.99) for colon cancer. Similarly, moving during work was associated with lower CRC risk than all other body postures – sitting, standing, and sitting/standing – combined; the multivariable HR (95% CI) was 0.85 (0.68–1.04) for CRC and 0.72 (0.50-1.00) for rectal cancer (data not shown).

Table 4 shows the combined impact of walking activity and job type as well as walking activity and body posture during work on CRC risk. Compared to office workers walking < 1h/d, the HR (95% CI) for incident CRC among non-office workers was 0.74 (0.54–1.01) for respondents walking < 1h/d, and 0.67 (0.49–0.91) for respondents walking ≥ 1h/d (Model 3). Similar associations were observed for incident colon cancer risk; the corresponding HRs (95% CIs) were 0.61 (0.42–0.89) and 0.60 (0.42–0.87), respectively. The p-value for interaction between walking activity and job type was 0.53 for CRC, 0.04 for colon cancer, and 0.14 for rectal cancer risk. Participants who reported moving body posture during work and ≥ 1h/d walking time had the lowest CRC and rectal cancer risks (reference: sitting, standing, or sitting/standing body posture during work with < 1h/d walking time); the multivariable HR (95% CI) was 0.72 (0.55–0.95) for CRC and 0.64 (0.41-1.00) for rectal cancer. The p-value for interaction between walking time and body posture during work was 0.27 for CRC, 0.18 for colon cancer, and 0.98 for rectal cancer risk.

Table 4

Combination of walking activity with job type or body posture during work and risk of incident colorectal cancer among Japanese men and women
	Job type				Walking > = 1 h/d
	Office work		Non-office work		No movement during work		Moving during work
	Walking < 1 h/d	Walking > = 1 h/d	Walking < 1 h/d	Walking > = 1 h/d	Walking < 1 h/d	Walking > = 1 h/d	Walking < 1 h/d	Walking > = 1 h/d
Participants, n	2965	1269	10140	12523	9178	6803	3927	6989
Person-year	45206	19996	145411	187305	136336	103290	54281	104011
Colorectal cancer, n	63	20	148	192	146	109	65	103
Model 1	1.00	0.74 (0.45–1.23)	0.71 (0.52–0.95)	0.64 (0.48–0.86)	1.00	0.94 (0.73–1.21)	0.94 (0.69–1.27)	0.72 (0.55–0.94)
Model 2	1.00	0.75 (0.45–1.24)	0.74 (0.54-1.00)	0.66 (0.48–0.89)	1.00	0.94 (0.73–1.21)	0.94 (0.69–1.28)	0.71 (0.54–0.93)
Model 3	1.00	0.76 (0.46–1.26)	0.74 (0.54–1.01)	0.67 (0.49–0.91)	1.00	0.95 (0.74–1.23)	0.94 (0.70–1.28)	0.72 (0.55–0.95)
Colon cancer, n	44	9	88	126	87	68	45	67
Model 1	1.00	0.46 (0.26–0.94)	0.56 (0.39–0.81)	0.56 (0.39–0.80)	1.00	0.97 (0.71–1.34)	1.05 (0.73–1.53)	0.76 (0.54–1.07)
Model 2	1.00	0.47 (0.23–0.97)	0.60 (0.41–0.88)	0.59 (0.41–0.86)	1.00	0.99 (0.72–1.36)	1.09 (0.75–1.59)	0.77 (0.54–1.08)
Model 3	1.00	0.48 (0.23–0.98)	0.61 (0.42–0.89)	0.60 (0.42–0.87)	1.00	1.00 (0.72–1.37)	1.09 (0.75–1.59)	0.78 (0.55–1.10)
Rectal cancer, n	19	11	60	66	59	41	20	36
Model 1	1.00	1.44 (0.69–3.03)	1.06 (0.63–1.79)	0.83 (0.49–1.40)	1.00	0.90 (0.60–1.34)	0.75 (0.45–1.27)	0.66 (0.43–1.03)
Model 2	1.00	1.41 (0.67–2.98)	1.06 (0.62–1.80)	0.80 (0.46–1.37)	1.00	0.86 (0.57–1.29)	0.72 (0.43–1.22)	0.63 (0.40–0.98)
Model 3	1.00	1.43 (0.68–3.02)	1.05 (0.62–1.80)	0.81 (0.47–1.39)	1.00	0.89 (0.59–1.32)	0.72 (0.42–1.22)	0.64 (0.41-1.00)

Model 1: adjusted for age, sex and area of residence.

Model 2: further adjusted for body mass index, history of diabetes, family history of cancer, education, occupation, stool habit, hours of watching TV, smoking habit, ethanol intake, and meat, vegetable, total dietary fiber, folate, and total energy intakes.

Model 3: In case of job type, further adjusted for sports activity and body posture during work; P-interaction = 0.53 for colorectal cancer, 0.04 for colon cancer, and 0.14 for rectal cancer. In case of body posture during work, further adjusted for sports activity and job type; P-interaction = 0.27 for colorectal cancer, 0.18 for colon cancer, and 0.98 for rectal cancer.

When creating eight cross-matched PA categories combining walking time, job type, and body posture during work (Online Resource 3), compared to office workers mainly sitting or standing during work and walking < 1h/d, the HR (95% CI) for colon cancer was 0.62 (0.40–0.97) among non-office workers walking < 1h/d, 0.41 (0.17–0.98) among office workers walking ≥ 1h/d, and 0.55 (0.36–0.86) among non-office workers walking ≥ 1h/d. The p-values for interactions among all possible combinations of walking time, job type, and body posture during work were > 0.01 for all outcomes, except for walking time with job type, where the p-interaction was 0.02 for colon cancer risk.

This nationally representative longitudinal study found that higher leisure-time and occupational PA was associated with lowered CRC risk among middle-aged and older Japanese. It also added evidence on the potential synergistic effect of job type and daily walking activity in preventing colon cancer and the benefits of a more active working environment for reduced rectal cancer risk.

The findings are in line with the previously published literature suggesting a positive association between PA and reduced CRC risk, observed in both Japanese [8, 16, 17] and non-Japanese populations [6, 7, 9–11]. In a systematic review and meta-analysis of 14 published articles, the pooled relative risk (RR) for colon cancer was 0.80 (0.67–0.96) among men and 0.86 (0.76–0.98) among women, comparing the lowest versus highest categories of leisure-time PA [18]. Another meta-analysis of 21 articles showed a 27% risk-reduction of colon cancer among the most versus the least physically active participants [19]. In a Norwegian population-based cohort study, a leisure-time PA level equivalent to ≥ 4h weakly walking time compared to a sedentary lifestyle was associated with a RR of 0.62 (95% CI: 0.40–0.97) for developing colon cancer [20]. The Miyagi cohort study conducted in the northern region of Japan found that walking ≥ 1h/d during the year preceding the baseline survey was associated with 44% and 62% reduced risk of CRC and colon cancer, respectively, after 7 years of follow-up among men; however, this association was not evident among women [16]. The authors attributed the null findings among women to limited statistical power [16] and potential differences in walking pace between men and women [21]. Similarly, in the Japan Public Health Center-based (JPHC) study, the multivariable HRs (95% CIs) for colon cancer were 0.58 (0.39–0.87) among men and 0.89 (0.54–1.49) among women, comparing the highest metabolic equivalent (MET) hours per day quartile to the lowest [8]. The authors emphasized in their discussion that the observed gender difference could be due to possible misclassifications of PA levels among women whose PA level was mainly attributed to housework, as opposed to the more common occupational PA among men. In our analyses, there was no significant interaction between sex and PA (P > 0.1). However, after stratification by sex, the 95% CIs of the risk estimates became inflated due to the loss of statistical power among women (data not shown).

In the current study, office workers were at a significantly higher risk of incident CRC and colon cancer than non-office workers. Likewise, previous publications found that workers with sedentary jobs showed an increased CRC risk, especially for colon cancer [9–11]. In an extensive study of 1.1 million Swedish men followed-up for 19 years, the RR (90% CI) of colon cancer among men with sedentary work compared to men with more physically demanding occupations was 1.3 (1.2–1.5) [22]. Similar findings were reported in other Swedish [11], American [23], and Turkish [24] studies.

Body posture during work was suggested to be a proxy measure for occupational PA level [25]. A large census-based Canadian study of 1,108,410 men and 942,905 women (mean age: 41.7 and 40.2 years, respectively) found that respondents who mainly sat during work had an increased risk of developing colon cancer compared to those reporting other working body postures. The multivariable HR (95% CI) was 0.93 (0.89–0.98) among men and 0.99 (0.93–1.06) among women during 17.7-years of follow-up [25]. A meta-analysis of 28 epidemiological studies that identified 46,071 new CRC cases among 7,84,339 participants reported that a 2h-increment in daily occupational sitting time was associated with a 4% higher CRC risk (RR = 1.04 95% CI: 1.01–1.08) [26]. In our study, respondents whose work required “moving” tended to have a reduced CRC and rectal cancer risk, especially among those who also reported a walking time of ≥ 1h/d.

To our knowledge, this is the first study to examine the combined effects of leisure-time PA, body posture during work, and job type on incident CRC risk in Asia. Our findings suggested a potential synergistic effect between walking time and job type for reduced colon cancer risk and an additive effect of walking time, job type, and body posture during work for reduced CRC and rectal cancer risk. Previously, Thune and Lund in Norway [20] created a total activity scale by summing recreational and occupational physical activities. Implementing the overall PA scale, they observed that the HRs (95% CIs) for colon cancer risk among physically active versus sedentary participants was 0.63 (0.39–1.04; p-trend = 0.04) and 0.66 (0.40–1.10; p-trend = 0.04) among middle-aged and older women and men, respectively. Similarly, Parent et al. in Canada [9] reported an HR of 0.83 (95% CI: 0.63–1.09) for colon cancer risk among respondents with high versus low overall PA – including both leisure-time and occupational activities. There are several proposed pathways to explain these observed associations. PA was linked to shorter gastrointestinal transit time as well as lowered amounts of secreted bile acids and prostaglandins, reducing not only the number of colonic carcinogens but also the exposure time of the intestinal cells to these carcinogens [12]. Also, PA was associated with enhanced immune function, reduced bile acid production, modulated gastrointestinal and pancreatic hormone profiles, and lowered circulating insulin and insulin-like growth factor levels, which are potential cell proliferation and tumor growth stimulators [12].

The current study’s strengths include its community-based longitudinal design with large sample size and the extensive examination of the independent and combined effects of leisure-time and occupational PA on incident CRC risk. However, some important limitations should also be noted. Leisure-time and occupational PA were assessed at baseline. Unmeasured changes in PA levels during the follow-up period might have led to misclassification bias. Moreover, PA measures were self-reported, indicating the possibility of measurement bias; however, the validity of self-reported PA was shown to be satisfactory among Japanese [27]. Despite the adjustment for a wide range of factors – including important dietary variables that were commonly neglected in many previous reports, even though higher meat and total calorie intakes were linked to high CRC risk, while higher vegetable, dietary fiber, and folate intakes were associated with reduced CRC risk – the possibility of residual confounding cannot be eliminated.

In this large Japanese cohort study, daily time spent waking and moving during work were associated with reduced CRC risk, especially for rectal cancer. In contrast, office work was associated with increased CRC risk, mainly for colon cancer. Also, combining leisure-time and occupational physical activities with job type suggested potential synergistic effects between walking activity and non-office work for reduced colon cancer risk, and additive effects of walking activity and moving during work for reduced rectal cancer risk. These findings imply that increasing the daily walking time or changing the body posture (from sitting to moving) of office and other sedentary workers may be means to reduce the CRC risk in the population.

Funding: This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) (Monbusho), Grants-in-Aid for Scientific Research on Priority Areas of Cancer, and Grants-in-Aid for Scientific Research on Priority Areas of Cancer Epidemiology from MEXT (MonbuKagaku-sho) (Nos. 61010076, 62010074, 63010074, 1010068, 2151065, 3151064, 4151063, 5151069, 6279102, 11181101, 17015022, 18014011, 20014026, 20390156, 26293138 and 16H06277). This research was also supported by a grant-in-aid from the Ministry of Health, Labour and Welfare, Health and Labor Sciences research grants, Japan (Research on Health Services: H17-Kenkou-007, Comprehensive Research on Cardiovascular Disease and Life-Related Disease: H18-Junkankitou[Seishuu]-Ippan-012, Comprehensive Research on Cardiovascular Disease and Life-Related Disease: H19-Junkankitou [Seishuu]-Ippan-012, Comprehensive Research on Cardiovascular and Life-Style Related Diseases: H20-Junkankitou [Seishuu]-Ippan-013, Comprehensive Research on Cardiovascular and Life–Style Related Diseases: H23-Junkankitou [Seishuu]-Ippan-005), an Intramural Research Fund (22-4-5) for Cardiovascular Diseases of National Cerebral and Cardiovascular Center, Comprehensive Research on Cardiovascular and Life-Style Related Diseases (H26-Junkankitou [Seisaku]-Ippan-001) and H29-Junkankitou [Seishuu]-Ippan-003) and 20FA1002.

Conflict of interest: None. All authors have read the journal's policy on conflicts of interest.

Ethics approval: The ethical review boards of Osaka University and Hokkaido University has approved this research.

Consent to participate: Informed consent was obtained from participants/community representatives.

Consent for publication: Not applicable.

Availability of data and material: Upon reasonable request of the study’s steering committee.

Code availability: Not applicable.

Authors’ contributions: ESE designed the research, analyzed the data, and drafted the manuscript, NH reviewed the manuscript, TA and IH designed the research and reviewed the manuscript. All authors have read the journal's authorship agreement.

Acknowledgments: The authors thank all staff members involved in this study for their valuable help in conducting the baseline survey and follow-up. Also, we would like to thank our colleague Dr. Krisztina Gero of Harvard School of Public Health for her help in editing the language of this research.

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Walking Time, Sports Activity, Job Type, and Body Posture During Work in Relation to Incident Colorectal Cancer: The JACC Prospective Cohort Study

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