1. Evaluation of some risk factors (e.g. smoking, heavy metal exposure, and organophosphorus exposure) on CRC.
2. Estimation of KRAS and BRAF genes mutations associated with CRC.
3. Association between different risk factors and gene mutations on different types of CRC.

• Colorectal cancer (CRC) ranks as the third most common cancer globally and second in terms of mortality (Bray et al., 2018). CRC is the 7th commonest cancer in Egypt, representing 3.47% of male cancers and 3% of female cancers (Metwally et al.,2018).
• Studies have provided that rising CRC rates are associated with increased alcohol use, physical inactivity, high intake of fat, red and processed meat, and processed foods; and low intake of fiber (Zhou and Rifkin, 2021).
• Smoking is an established risk factor for colorectal adenomas as well as CRC incidence and mortality, which suggests that it may affect the prognosis of CRC patients as well (Walter et al., 2014).
• Heavy metals are natural components of the earth's crust, which, if released into the environment, can persist for many years (Wu et al., 2016). The most toxic elements are arsenic, cadmium, chromium, copper, mercury, and lead with the majority of them being classified as certainly or probably carcinogenic (Forte et al., 2020).
• Pesticides that are applied to farms can remain in the environment for longer than intended (Sjerps et al., 2019). Pesticides increase the risk of cancer through a variety of mechanisms including genotoxicity, epigenetic effects, hormonal action, and immunotoxicity (Lyons and Watterson, 2010).
• Of the key genes of CRC, KRAS mutations are the most widely known, as they are mainly localized in codons 12 and 13, which were among the first linked to the pathogenesis of colon cancer (Kudryavtseva et al., 2016). BRAF is an oncogene located on chromosome 7 for which gain of function mutations in multiple solid tumors, such as colon cancer (Frisone et al., 2020).

Inclusion Criteria:

- 1. Patients who are recently diagnosed with CRC based on clinical and pathological examinations.

2. Control subjects will be CRC-free, based on the clinical history and physical examination.

Exclusion Criteria:

1 - Patient refuses to be enrolled in the study. 2. Subjects with cancer metastasized from other tissues to the colon. (colon is the site of metastasis)

the patient group is 50 patients who are recently diagnosed with CRC based on clinical and pathological examinations.

THE control group is 50 subjects who will be CRC-free, based on the clinical history and physical examination.