The effect of hereditary and lifestyle risk factors on colorectal adenoma and colorectal cancer risk

Abstract

Colorectal cancer (CRC) is currently the third most common cancer and ranks second on the cancer mortality causes worldwide and a multifactorial disease resulting from a combination of hereditary and lifestyle factors. Serrated polyps (SP) and conventional adenomas (CA) are established precursor lesions for colorectal cancer (CRC). However, the interaction between family history of CRC and modifiable lifestyle factors (diet, smoking, physical activity, alcohol consumption, and BMI) on CRC and CA/SP risk is not well documented in the literature. Moreover, although a number of risk factors are established for serrated polyps (SPs) and colorectal adenoma (CAs), the preventable incidence (population attributable fraction - PAF) associated with these modifiable factors remains unclear. Therefore, the overall goal of this thesis is to investigate the complex relationship between lifestyle, family risk factor risk factors, and CRC/CA/SP as well as the PAF of CA/SP caused by these risk factors. The first study (Chapter 1) aimed to determine if adherence to a healthy lifestyle offsets the increased risk of CRC associated with family history. Using data from the Nurses' Health Study and the Health Professionals Follow-up Study from 1986 to 2020, we created a healthy lifestyle index based on several lifestyle factors for CRC (diet, smoking, physical activity, alcohol consumption, BMI, and calcium intake) and used Cox regression to estimate adjusted hazard ratios and absolute risk prediction for the association between the exposures and CRC. We found that adhering to a healthy lifestyle can decrease absolute CRC risk in individuals with and without family history. Particularly, higher healthy lifestyle index may offset the risk associated with family history in men. Our data support the importance of recommending adherence to healthy lifestyle in clinical practice for individuals with CRC family history, especially among males. The second study (Chapter 2) aimed to determine whether lifestyle modifies the association between family history of CRC and precursor lesions of CRC (SP and CA). For this study, we used data from the Nurses' Health investigation (NHS), Nurses' Health Study 2 (NHS2), and the Health Professionals Follow-up Study (HPFS) and applied the same healthy lifestyle index. We found that the absolute risk of polyps decreases with extended adherence to a healthy lifestyle in both the family history and non-family history groups. When it comes specifically to synchronous SPs and CAs, either kind of SP or CA, or any kind of polyp, the impact of family history was decreasing as people got healthier. Our results underline how important it is to advise medical professionals to advise individuals with a family history of CRC to maintain healthy lifestyles. The third study (Chapter 3) aimed to determine the preventable fraction of SPs and CAs incidence for established modifiable colorectal cancer risk factors in the United States. We estimated the PAF in three prospective cohort studies: Nurses' Health Study (NHS), Nurses' Health Study 2 (NHS2), and the Health Professionals Follow-up Study (HPFS). Modifiable lifestyle factors identified by the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) with convincing or probable evidence were selected (convincing evidence: physical activity, processed meat intake, alcohol consumption, body mass index (BMI) and probable evidence: total fiber intake, calcium intake, red meat intake) as well as smoking. In summary, nearly half of SPs and advanced adenoma cases as well as more than a quarter of CAs cases were attributable to all eight lifestyle factors. Our findings confirm the significance of maintaining a healthy lifestyle to prevent colorectal polyps and, in the long-term, CRC.