Cancer Res Treat.  2019 Jul;51(3):1033-1040. 10.4143/crt.2018.447.

Genetic Risk Score, Combined Lifestyle Factors and Risk of Colorectal Cancer

• Cho YA
• Lee J
• Oh JH
• Chang HJ
• Sohn DK
• Shin A
• Kim J

• KMID: 2454295
• DOI: http://doi.org/10.4143/crt.2018.447

Abstract

PURPOSE
Both genetic and lifestyle factors contribute to the risk of colorectal cancer, but each individual factor has a limited effect. Therefore, we investigated the association between colorectal cancer and the combined effects of genetic factors or/and lifestyle risk factors.
MATERIALS AND METHODS
In a case-control study of 632 colorectal cancer patients and 1,295 healthy controls, we quantified the genetic risk score for colorectal cancer using 13 polymorphisms. Furthermore, we determined a combined lifestyle risk score including obesity, physical activity, smoking, alcohol consumption, and dietary inflammatory index. The associations between colorectal cancer and risk score using these factors were examined using a logistic regression model.
RESULTS
Higher genetic risk scores were associated with an increased risk of colorectal cancer (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.89 to 3.49 for the highest tertile vs. lowest tertile). Among the modifiable factors, previous body mass index, physical inactivity, heavy alcohol consumption, and a high inflammatory diet were associated with an increased risk of colorectal cancer. A higher lifestyle risk score was associated with an increased risk of colorectal cancer (OR, 5.82; 95% CI, 4.02 to 8.44 for the highest tertile vs. lowest tertile). This association was similar in each genetic risk category.
CONCLUSION
Adherence to a healthy lifestyle is associated with a substantially reduced risk of colorectal cancer regardless of individuals' genetic risk.

Keyword

Colorectal cancer; Genes; Lifestyle; Risk score

MeSH Terms

Alcohol Drinking
Body Mass Index
Case-Control Studies
Colorectal Neoplasms*
Diet
Humans
Life Style*
Logistic Models
Motor Activity
Obesity
Risk Factors
Smoke
Smoking
Smoke

Reference

References

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65:87–108.

2. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. Environmental and heritable factors in the causation of cancer: analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000; 343:78–85.

3. Jung KJ, Won D, Jeon C, Kim S, Kim TI, Jee SH, et al. A colorectal cancer prediction model using traditional and genetic risk scores in Koreans. BMC Genet. 2015; 16:49.

4. Zhang B, Jia WH, Matsuda K, Kweon SS, Matsuo K, Xiang YB, et al. Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk. Nat Genet. 2014; 46:533–42.

5. Jia WH, Zhang B, Matsuo K, Shin A, Xiang YB, Jee SH, et al. Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer. Nat Genet. 2013; 45:191–6.

6. Houlston RS, Cheadle J, Dobbins SE, Tenesa A, Jones AM, Howarth K, et al. Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nat Genet. 2010; 42:973–7.

7. Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Int J Cancer. 2009; 125:171–80.

8. Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009; 59:366–78.

9. Aran V, Victorino AP, Thuler LC, Ferreira CG. Colorectal cancer: epidemiology, disease mechanisms and interventions to reduce onset and mortality. Clin Colorectal Cancer. 2016; 15:195–203.

10. Iwasaki M, Tanaka-Mizuno S, Kuchiba A, Yamaji T, Sawada N, Goto A, et al. Inclusion of a genetic risk score into a validated risk prediction model for colorectal cancer in Japanese men improves performance. Cancer Prev Res (Phila). 2017; 10:535–41.

11. Kirkegaard H, Johnsen NF, Christensen J, Frederiksen K, Overvad K, Tjonneland A. Association of adherence to lifestyle recommendations and risk of colorectal cancer: a prospective Danish cohort study. BMJ. 2010; 341:c5504.

12. Platz EA, Willett WC, Colditz GA, Rimm EB, Spiegelman D, Giovannucci E. Proportion of colon cancer risk that might be preventable in a cohort of middle-aged US men. Cancer Causes Control. 2000; 11:579–88.

13. Wei EK, Colditz GA, Giovannucci EL, Fuchs CS, Rosner BA. Cumulative risk of colon cancer up to age 70 years by risk factor status using data from the Nurses' Health Study. Am J Epidemiol. 2009; 170:863–72.

14. Driver JA, Gaziano JM, Gelber RP, Lee IM, Buring JE, Kurth T. Development of a risk score for colorectal cancer in men. Am J Med. 2007; 120:257–63.

15. Ahn Y, Kwon E, Shim JE, Park MK, Joo Y, Kimm K, et al. Validation and reproducibility of food frequency questionnaire for Korean genome epidemiologic study. Eur J Clin Nutr. 2007; 61:1435–41.

16. Cho YA, Lee J, Oh JH, Shin A, Kim J. Dietary inflammatory index and risk of colorectal cancer: a case-control study in Korea. Nutrients. 2016; 8:E469.

17. Shivappa N, Steck SE, Hurley TG, Hussey JR, Hebert JR. Designing and developing a literature-derived, populationbased dietary inflammatory index. Public Health Nutr. 2014; 17:1689–96.

18. Song N, Shin A, Park JW, Kim J, Oh JH. Common risk variants for colorectal cancer: an evaluation of associations with age at cancer onset. Sci Rep. 2017; 7:40644.

19. Brautbar A, Pompeii LA, Dehghan A, Ngwa JS, Nambi V, Virani SS, et al. A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies. Atherosclerosis. 2012; 223:421–6.

20. Stevens J, Juhaeri , Cai J. Changes in body mass index prior to baseline among participants who are ill or who die during the early years of follow-up. Am J Epidemiol. 2001; 153:946–53.

21. Liang PS, Chen TY, Giovannucci E. Cigarette smoking and colorectal cancer incidence and mortality: systematic review and meta-analysis. Int J Cancer. 2009; 124:2406–15.

22. Dunlop MG, Tenesa A, Farrington SM, Ballereau S, Brewster DH, Koessler T, et al. Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42,103 individuals. Gut. 2013; 62:871–81.

23. Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. 2008; 25:2097–116.

24. Bardou M, Barkun AN, Martel M. Obesity and colorectal cancer. Gut. 2013; 62:933–47.

25. Shiels MS, Katki HA, Freedman ND, Purdue MP, Wentzensen N, Trabert B, et al. Cigarette smoking and variations in systemic immune and inflammation markers. J Natl Cancer Inst. 2014; 106:dju294.

26. Bufill JA. Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med. 1990; 113:779–88.

27. Iacopetta B. Are there two sides to colorectal cancer? Int J Cancer. 2002; 101:403–8.

28. Shin A, Joo J, Bak J, Yang HR, Kim J, Park S, et al. Site-specific risk factors for colorectal cancer in a Korean population. PLoS One. 2011; 6:e23196.

29. Wei EK, Giovannucci E, Wu K, Rosner B, Fuchs CS, Willett WC, et al. Comparison of risk factors for colon and rectal cancer. Int J Cancer. 2004; 108:433–42.

30. Yeoh KG, Ho KY, Chiu HM, Zhu F, Ching JY, Wu DC, et al. The Asia-Pacific Colorectal Screening score: a validated tool that stratifies risk for colorectal advanced neoplasia in asymptomatic Asian subjects. Gut. 2011; 60:1236–41.