The power of a healthy lifestyle for cancer prevention: the example of colorectal cancer

Xuechen Chen; Jie Ding; Hengjing Li; Prudence R. Carr; Michael Hoffmeister; Hermann Brenner

doi:10.20892/j.issn.2095-3941.2022.0397

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Figure 1
Flowchart of inclusion of study participants. BMI, body mass index; CRC, colorectal cancer.

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Table 1

Characteristics of the study population according to case and control status

Characteristics	CRC cases, n (%)	Controls, n (%)	P value⁸
Total	4,844	3,964
Age (years), median (Q1, Q3)	69 (61, 76)	69 (62, 76)
Gender
Female	1,897 (39.2)	1,517 (38.3)
Male	2,947 (60.8)	2,447 (61.7)
School education (years)¹			<0.0001
< 9	3,172 (65.5)	2,185 (55.5)
9–10	855 (17.7)	837 (21.1)
> 10	808 (16.7)	936 (23.6)
Smoking			<0.0001
Current or former (≥ 30 pack years)	1,081 (22.3)	706 (17.8)
Never or former (< 30 pack years)	3,763 (77.7)	3,258 (82.2)
Alcohol consumption (g/d), mean (SE)²
Women	5.1 (0.2)	5.7 (0.2)	<0.0001
Men	22.4 (0.4)	19.2 (0.4)	<0.0001
Diet quality score, mean (SE)	30.5 (0.1)	32.1 (0.1)	<0.0001
Physical activity (MET-hours/week), mean (SE)³	40.3 (0.6)	45.8 (0.7)	<0.0001
BMI (kg/m²)⁴			<0.0001
Overweight or obese (≥ 25)	3,403 (70.3)	2,460 (62.1)
Healthy weight (18.5 to < 25)	1,441 (29.7)	1,504 (37.9)
Healthy lifestyle score			<0.0001
0	54 (1.1)	18 (0.5)
1	345 (7.1)	174 (4.4)
2	1,130 (23.3)	686 (17.3)
3	1,726 (35.6)	1,347 (34.0)
4	1,237 (25.5)	1,182 (29.8)
5	352 (7.3)	557 (14.1)
Family history of CRC⁵	710 (14.7)	431 (10.9)	<0.0001
History of colonoscopy	1,282 (26.5)	2,386 (60.2)	<0.0001
Participation in routine health check-ups⁶	4,123 (85.1)	3,646 (92.0)	<0.0001
Regular use of NSAIDs	1,394 (28.8)	1,509 (38.1)	<0.0001
Cancer sites
Colon cancer	2,950 (60.9)	/
Rectum cancer	1,894 (39.1)	/
Cancer stages⁷
I	1,110 (22.9)	/
II	1,476 (30.5)	/
III	1,529 (31.6)	/
IV	686 (14.2)	/

¹Data are missing for 15 participants. ²Lifetime average alcohol consumption, calculated on the basis of self-recalled alcohol consumption at the ages of 20, 30, 40, 50, 60, 70, and 80 years. ³Non-occupational physical activity from the most recent decade preceding the date of diagnosis/interview. ⁴BMI at approximately 10 years before diagnosis/interview. ⁵Data are missing for 6 participants. ⁶Data are missing for 32 participants. ⁷Data are missing for 43 cases. ⁸P values are not reported for the matching factors. BMI, body mass index; CRC, colorectal cancer; MET, metabolic equivalent task; NSAID, non-steroidal anti-inflammatory drug; Q, quartile; SE, standard error.

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Table 2

ORs and GREs for risk of colorectal cancer according to individual lifestyle factors

Lifestyle factor	Points	Description	CRC cases, n (%)	Controls, n (%)	OR (95% CI)¹	OR (95% CI)²	GRE (95% CI)
Smoking	0	Smoking: current smoker or former smoker (≥ 30 pack years)	1,079 (22.4)	704 (17.9)	Ref.	Ref.	Ref.
	1	Non-smoking: never smoker or former smoker (< 30 pack years)	3,735 (77.6)	3,237 (82.1)	0.75 (0.67, 0.83)	0.86 (0.76, 0.97)	−12.3 (−22.5, −2.2)
P-interaction with PRS³ = 0.61
Alcohol consumption	0	Did not meet recommendations on alcoholic drinks⁴	1,266 (26.3)	911 (23.1)	Ref.	Ref.	Ref.
	1	Met recommendation on alcoholic drinks⁴	3,548 (73.7)	3,030 (76.9)	0.83 (0.75, 0.92)	0.85 (0.76, 0.95)	−13.3 (−22.6, −4.0)
P-interaction with PRS³ = 0.45
Diet quality	0	Unhealthy diet quality: diet quality score < 34⁵	3,190 (66.3)	2,138 (54.3)	Ref.	Ref.	Ref.
	1	Healthy diet quality: diet quality score ≥ 34⁵	1,624 (33.7)	1,803 (45.7)	0.59 (0.54, 0.65)	0.69 (0.63, 0.76)	−30.4 (−39.4, −21.3)
P-interaction with PRS³ = 0.17
Physical activity	0	Did not meet physical activity guidelines⁶	753 (15.6)	486 (12.3)	Ref.	Ref.	Ref.
	1	Met physical activity guidelines⁶	4,061 (84.4)	3,455 (87.7)	0.75 (0.66, 0.84)	0.95 (0.83, 1.09)	−4.2 (−15.6, 7.2)
P-interaction with PRS³ = 0.35
BMI	0	Overweight or obese (BMI ≥ 25 kg/m²)	3,384 (70.3)	2,447 (62.1)	Ref.	Ref.	Ref.
	1	Healthy weight (18.5 < BMI < 25 kg/m²)	1,430 (29.7)	1,494 (37.9)	0.67 (0.61, 0.74)	0.67 (0.60, 0.74)	−32.8 (−42.2, −23.3)
P-interaction with PRS³ = 0.36

¹Adjusted for matching factors age and gender. ²Additionally adjusted for school education, family history of CRC, history of colonoscopy, participation in routine health check-ups, use of nonsteroidal anti-inflammatory drugs, PRS (per 10 percentiles, continuous), and mutual adjustment for the other lifestyle factors. ³Interactions were tested by inclusion of a cross-product term of the PRS (continuous variable) and the individual lifestyle factors (categorical variable) along with the main effect terms in multivariable models. ⁴World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) (2007) Recommendation on alcoholic drinks: ≤ 24 g/day for men and ≤ 12 g/day for women. ⁵Diet quality score in the highest 40%. ⁶The WHO Global Recommendations on Physical Activity for Health (2010) recommend that adults engage in at least 150 min of moderate-intensity or 75 min of vigorous-intensity aerobic physical activity throughout the week, or an equivalent combination of moderate and vigorous intensity physical activity (at least ∼500 MET min). BMI, body mass index; CI, confidence intervals; CRC, colorectal cancer; GRE, genetic risk equivalent; OR, odds ratio; PRS, polygenic risk score; Ref., reference.

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Table 3

Individual associations of the polygenic risk score and the healthy lifestyle score with colorectal cancer risk

Variables	CRC cases, n (%)	Controls, n (%)	OR (95%CI)¹	OR (95% CI)²	GRE (95% CI)
PRS³
Low	1,026 (21.3)	1,317 (33.4)	Ref.	Ref.
Moderate	1,544 (32.1)	1,313 (33.3)	1.51 (1.35, 1.68)	1.54 (1.37, 1.74)
High	2,244 (46.6)	1,311 (33.3)	2.20 (1.97, 2.44)	2.21 (1.97, 2.48)
PRS (per 10 percentile increase)			1.13 (1.11, 1.15)	1.13 (1.11, 1.15)
Healthy lifestyle score
0–2	1,519 (31.6)	876 (22.2)	Ref.	Ref.
3	1,715 (35.6)	1,337 (33.9)	0.72 (0.65, 0.81)	0.78 (0.69, 0.88)	−20.3 (−30.6, −10.0)
4	1,233 (25.6)	1,175 (29.8)	0.57 (0.51, 0.65)	0.63 (0.55, 0.72)	−37.8 (−49.7, −25.9)
5	347 (7.2)	553 (14.0)	0.33 (0.28, 0.39)	0.38 (0.32, 0.46)	−79.2 (−97.3, −61.1)
Per 1-point increase			0.74 (0.71, 0.78)	0.78 (0.74, 0.81)	−20.3 (−25.0, −15.7)
P value for interaction between PRS and healthy lifestyle score⁴ = 0.88/0.39

¹Adjusted for age and gender. ²Additionally adjusted for school education, family history of CRC, history of colonoscopy, participation in routine health check-ups, use of nonsteroidal anti-inflammatory drugs, healthy lifestyle score (categorical variable, for the analysis of PRS), and PRS (continuous variable with per 10 percentile increase, for the analysis of healthy lifestyle score). ³PRS was categorized into low, moderate, and high levels according to tertiles of PRS among controls. ⁴Interactions were tested by inclusion of a cross-product of the PRS (categorical variable/continuous variable) and the healthy lifestyle score (categorical variable) along with the main effect terms in multivariable models. CI, confidence intervals; CRC, colorectal cancer; OR, odds ratio; PRS, polygenic risk score; Ref., reference.

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Table 4

ORs and GREs for colorectal cancer risk according to the healthy lifestyle score in subgroups by cancer site and stage

CRC	Healthy lifestyle score	Cases, n (%)	Controls, n (%)	OR (95% CI)¹	GRE (95% CI)
Colon cancer	0–2	885 (30.2)	876 (22.2)	Ref.	Ref.
	3	1,060 (36.2)	1,337 (33.9)	0.79 (0.69, 0.91)	−19.3 (−30.7, −7.8)
	4	770 (26.3)	1,175 (29.8)	0.63 (0.55, 0.73)	−37.8 (−51.1, −24.6)
	5	217 (7.4)	553 (14.0)	0.39 (0.32, 0.47)	−77.0 (−97.3, −56.8)
	Per 1-point increase			0.78 (0.74, 0.82)	−20.3 (−25.5, −15.1)
Rectal cancer	0–2	634 (33.7)	876 (22.2)	Ref.	Ref.
	3	655 (34.8)	1,337 (33.9)	0.75 (0.64, 0.88)	−22.0 (−34.7, −9.2)
	4	463 (24.6)	1,175 (29.8)	0.61 (0.51, 0.73)	−37.7 (−52.5, −23.0)
	5	130 (6.9)	553 (14.0)	0.37 (0.29, 0.48)	−75.9 (−98.7, −53.0)
	Per 1-point increase			0.77 (0.73, 0.82)	−19.9 (−25.7, −14.2)
P value for heterogeneity between strata (3/4/5 points) = 0.41/0.57/0.83
CRC (stage I)	0–2	309 (28.0)	876 (22.2)	Ref.	Ref.
	3	401 (36.3)	1,337 (33.9)	0.87 (0.72, 1.04)	−11.4 (−26.5, 3.7)
	4	303 (27.4)	1,175 (29.8)	0.76 (0.62, 0.92)	−22.5 (−39.3, −5.6)
	5	92 (8.3)	553 (14.0)	0.49 (0.37, 0.64)	−58.4 (−84.0, −32.7)
	Per 1-point increase			0.84 (0.79, 0.90)	−14.3 (−20.7, −7.9)
CRC (stage II)	0–2	501 (34.1)	876 (22.2)	Ref.	Ref.
	3	548 (37.3)	1,337 (33.9)	0.74 (0.62, 0.87)	−24.6 (−39.0, −10.3)
	4	324 (22.1)	1,175 (29.8)	0.47 (0.39, 0.57)	−61.8 (−81.2, −42.4)
	5	96 (6.5)	553 (14.0)	0.32 (0.24, 0.42)	−93.2 (−121.7, −64.8)
	Per 1-point increase			0.71 (0.67, 0.76)	−28.0 (−35.6, −20.4)
CRC (stage III)	0–2	464 (30.6)	876 (22.2)	Ref.	Ref.
	3	505 (33.3)	1,337 (33.9)	0.74 (0.63, 0.88)	−24.6 (−39.1, −10.1)
	4	423 (27.9)	1,175 (29.8)	0.67 (0.56, 0.80)	−32.8 (−48.7, −16.9)
	5	124 (8.2)	553 (14.0)	0.43 (0.33, 0.55)	−69.1 (−93.3, −44.8)
	Per 1-point increase			0.81 (0.76, 0.86)	−17.2 (−23.4, −11.1)
CRC (stage IV)	0–2	234 (34.4)	876 (22.2)	Ref.	Ref.
	3	244 (35.8)	1,337 (33.9)	0.77 (0.62, 0.96)	−21.4 (−40.1, −2.6)
	4	170 (25.0)	1,175 (29.8)	0.60 (0.47, 0.76)	−41.8 (−64.6, −19.0)
	5	33 (4.8)	553 (14.0)	0.25 (0.16, 0.37)	−113.4 (−157.8, −69.0)
	Per 1-point increase			0.72 (0.66, 0.79)	−26.9 (−36.8, −17.0)
P value for heterogeneity between strata (3/4/5 points) = 0.23/0.00015/0.0018

¹Variables in the model included age, gender, school education, family history of CRC, history of colonoscopy, participation in routine health check-ups, use of nonsteroidal anti-inflammatory drugs, healthy lifestyle score, and PRS (per 10 percentiles, continuous). CI, confidence intervals; CRC, colorectal cancer; GRE, genetic risk equivalent; OR, odds ratio; PRS, polygenic risk score; Ref., reference.