Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies

Xiaoliang Wang^{1

2}, Kelli O'Connell³, Jihyoun Jeon⁴, Mingyang Song^{5

6}, David Hunter^{7

8}, Michael Hoffmeister⁹, Yi Lin¹, Sonja Berndt¹⁰, Hermann Brenner⁹, Andrew T Chan^{11

12}, Jenny Chang-Claude¹³, Jian Gong¹, Marc J Gunter¹⁴, Tabitha A Harrison¹, Richard B Hayes¹⁵, Amit Joshi^{7

16}, Polly Newcomb^{1

2}, Robert Schoen¹⁷, Martha L Slattery¹⁸, Ashley Vargas¹⁹, John D Potter^{1

2}, Loic Le Marchand²⁰, Edward Giovannucci^{5

6}, Emily White^{1

2}, Li Hsu¹, Ulrike Peters^{1

2}, Mengmeng Du³

Affiliations

¹ Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
² Epidemiology, University of Washington, Seattle, Washington, USA.
³ Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
⁴ Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Channing Division of Network Medicine, Harvard Medical School, Boston, Massachusetts, USA.
⁶ Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA.
⁷ Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA.
⁸ Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire, UK.
⁹ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
¹⁰ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
¹¹ Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹² Harvard Medical School, Boston, Massachusetts, USA.
¹³ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
¹⁴ Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
¹⁵ Epidemiology, New York University School of Medicine, New York, New York, USA.
¹⁶ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹⁷ Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
¹⁸ Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
¹⁹ Office of Disease Prevention, National Institutes of Health, Bethesda, Maryland, USA.
²⁰ Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, Hawaii, USA.

PMID: 31875139
PMCID: PMC6904202
DOI: 10.1136/bmjgast-2019-000339

Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies

Xiaoliang Wang et al. BMJ Open Gastroenterol. 2019.

. 2019 Dec 2;6(1):e000339.

doi: 10.1136/bmjgast-2019-000339. eCollection 2019.

Authors

Affiliations

¹ Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
² Epidemiology, University of Washington, Seattle, Washington, USA.
³ Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
⁴ Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Channing Division of Network Medicine, Harvard Medical School, Boston, Massachusetts, USA.
⁶ Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA.
⁷ Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA.
⁸ Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire, UK.
⁹ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
¹⁰ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
¹¹ Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹² Harvard Medical School, Boston, Massachusetts, USA.
¹³ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
¹⁴ Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
¹⁵ Epidemiology, New York University School of Medicine, New York, New York, USA.
¹⁶ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹⁷ Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
¹⁸ Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
¹⁹ Office of Disease Prevention, National Institutes of Health, Bethesda, Maryland, USA.
²⁰ Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, Hawaii, USA.

PMID: 31875139
PMCID: PMC6904202
DOI: 10.1136/bmjgast-2019-000339

Abstract

Objective: 'Environmental' factors associated with colorectal cancer (CRC) risk include modifiable and non-modifiable variables. Whether those with different non-modifiable baseline risks will benefit similarly from reducing their modifiable CRC risks remains unclear.

Design: Using 7945 cases and 8893 controls from 11 population-based studies, we combined 17 risk factors to characterise the overall environmental predisposition to CRC (environmental risk score (E-score)). We estimated the absolute risks (ARs) of CRC of 10 and 30 years across E-score using incidence-rate data from the Surveillance, Epidemiology, and End Results programme. We then combined the modifiable risk factors and estimated ARs across the modifiable risk score, stratified by non-modifiable risk profile based on genetic predisposition, family history and height.

Results: Higher E-score was associated with increased CRC risk (OR_quartile, 1.33; 95% CI 1.30 to 1.37). Across E-scores, 30-year ARs of CRC increased from 2.5% in the lowest quartile (Q1) to 5.9% in the highest (Q4) quartile for men, and from 2.1% to 4.5% for women. The modifiable risk score had a stronger association in those with high non-modifiable risk (relative excess risk due to interaction=1.2, 95% CI 0.5 to 1.9). For those in Q4 of non-modifiable risk, a decrease in modifiable risk reduced 30-year ARs from 8.9% to 3.4% for men and from 6.0% to 3.2% for women, a level lower or comparable to the average population risk.

Conclusions: Changes in modifiable risk factors may result in a substantial decline in CRC risk in both sexes. Those with high inherited risk may reap greater benefit from lifestyle modifications. Our results suggested comprehensive evaluation of environmental factors may facilitate CRC risk stratification.

Keywords: cancer prevention; colorectal cancer; epidemiology.

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Conflict of interest statement

Competing interests: MJG: where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

Figures

**Figure 1**
Associations of weighted study sex-specific quartiles of environmental risk scores and colorectal cancer risk among studies. P heterogeneity=0.0002; Adjusted for age, total energy consumption, history of screening, and education. Colo2&3, a case–control study from the University of Hawai’i; DACHS, Darmkrebs: chancen der Verhutüng durch Screening Study; DALS, diet, activity and lifestyle study; HPFS, Health Professionals Follow-up Study; MEC, multiethnic cohort; NHS, Nurses’ Health Study; PHS, Physicians’ Health Study; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; PMH, the hormones and colon cancer study; VITAL, Vitamins and Lifestyle Study; WHI, Women's Health Initiative.

**Figure 2**
(A) 10-year and (B) 30-year absolute risk of CRC for a 50-year old individual by E-score. (A) E-score included body mass index (kg/m²), height (cm), smoking (ever/never, pack-years), alcohol consumption (non-drinkers, 1–28 g/day, >28 g/day), physical activity (sedentary, yes/no), regular use of aspirin (yes/no), regular use of other non-steroidal anti-inflammatory drugs (yes/no), regular use of postmenopausal hormone in women (yes/no), sex-specific and study-specific quartiles of dietary factors (red meat, processed meat, fruits, vegetables, fibre, folate and calcium) and history of diabetes (yes/no). (B) Adjusted for age, study, total energy consumption, history of screening and education. CRC, colorectal cancer; E-score, environmental risk score.

**Figure 3**
Distribution of absolute risk associated with modifiable risk score (A) stratified by non-modifiable risk score quartiles (B) in the USA. Dashed lines indicate the average absolute risks of CRC for a 50-year-old person: 0.68% and 0.49% for 10-year absolute risk in men (A) and women (B), and 4.1% and 3.2% for 30-year absolute risk in men (C) and women (D), respectively. (A) Modifiable risk score included body mass index, sedentary, smoking, pack-years of smoking, intakes of alcohol, fibre, calcium, folate, processed meat, red meat, fruit and vegetables, use of aspirin and non-aspirin non-steroidal anti-inflammatory drugs and postmenopausal hormone use among women and diabetes. (B) Non-modifiable risk score included age, sex, height, family history of CRC, and common genetic predisposition based on 63 genome-wide association study (GWAS)-identified single-nucleotide polymorphisms. CRC, colorectal cancer.

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Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies

Affiliations

Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Full Text Sources