This study illustrated the possible role of lifestyle factors in colorectal carcinoma etiology in a developing country with a unique pattern in epidemiology – early onset, high proportion of rectal cancer, and low presence of adenomas.4-5,7
We observed that agricultural and industrial exposures were significantly associated with a higher risk of colorectal carcinoma. In women, parity and breastfeeding were inversely associated with colorectal cancer risk.
Our findings are in agreement with previous research regarding the impact of occupational exposures in colorectal cancer risk. Being exposed to industrial materials was associated with 2-4 times higher risk for large bowel cancer in Canada and China.13-14
Working in dusty environment for 10 years or longer was significantly associated with colorectal carcinoma in early adulthood (OR=2.0, 95% CI=1.0-4.0).15
Consistently, we observed that history of industrial exposures was more frequent in younger patients than older patients.
Rural residency and farming occupations have been associated with a lower risk of colorectal carcinoma when compared to urban residency and non-farming occupation.16-17
However, intense pesticide exposure may increase cancer risk among rural residents and farmers. Geographical distribution of high colorectal carcinoma incidence tends to be parallel with regions of high agricultural activity in the U.S.18-19
In China, villages with higher contents of polychlorinated biphenyl (PCB) and dichlorodiphenyltrichloroethane (DDT) in rice and soil samples were found with significantly higher incidence of colorectal carcinoma.20
The high consumption of fresh vegetables in the general population and the widespread use of pesticides in Egypt might alter colorectal cancer risk through dietary intake starting from early childhood.21-22
We have reported higher serum organochlorine pesticide levels in colorectal cancer patients from Egypt.8
Consistently, we observed that being exposed to pesticides and eating fresh food items from farm were significantly associated with a higher risk of colorectal carcinoma among Egyptian farmers in this study. Although no difference was found in agricultural exposures between the young and old patients, we think that intense environmental pollution and pesticide exposures may help to explain the unique pattern of early onset of colorectal carcinoma in Egypt.22
Our research have shown that colorectal tumors from younger Egyptian patients illustrated distinct molecular characteristics when compared to tumors from older Egyptian, HNPCC, and sporadic colorectal carcinoma patients in the U.S. and other countries.6-7,23-24
Future studies should be conducted to investigate the interaction between pesticide exposures and genes on altering colorectal carcinogenesis.
We also observed that higher fertility and prolonged lactation were inversely correlated with colorectal carcinoma, and the protective effects were not different by anatomic subsites. It has been hypothesized that hormonal changes correlated with pregnancy might interact with bile-acid or estrogen receptors, resulting in a reduced risk for colon cancer.25
However, conflicting results were showed in previous studies.25-28
Compared to women who had 1-2 live births, women who had 5 or more live births showed a significantly lower risk of colon cancer in the U.S. (OR=0.6, 95% CI=0.3-0.9), but this protective effect was found only in women under age 65, not in the older group.26
A more recent study in the U.S. found an inverse correlation between parity and rectal cancer (Ptrend
=0.05), but not for colon cancer (Ptrend
Only a study evaluated the possible correlation between breastfeeding and risk of colorectal carcinoma.28
Lifetime duration of lactation for 19 months or more was not associated with colorectal carcinoma when compared to never lactation.28
In addition to hormonal changes, the reduced risk of colorectal carcinoma in Egyptian women might also be correlated with environmental exposures. We have reported that Egyptian women who breastfed for 23.5 months or longer per live birth in average had lower levels of serum dichlorodiphenyldichloroethylene (DDE, P
This finding suggests that breastfeeding might protect women from the accumulation of environmental carcinogens by excreting these components to infants within the breast milk.10
In contrast to Egyptian women, women in Costa Rica have common use of contraceptives, low fertility rate, and short-term breastfeeding.29
Interestingly, significantly increased risks of rectal cancer (RR=1.9, 95% CI=1.1-3.3) and female hormone-related cancers (RR between 1.3 and 1.8) were associated with high pesticide exposure levels in Costa Rica women from rural counties.16
The connection between tobacco consumption and colorectal carcinoma remains inconclusive. We observed a null association between active smoking and overall colorectal carcinoma risk when compared with nonsmoking, and the association was in opposite direction by gender. Some factors may help explain these findings. First, there might be a 40-year induction period of cigarette smoking in colorectal carcinoma development.30-31
Ji et al. (2002) found no association between cigarette smoking and colorectal carcinoma in China, with relatively shorter duration (mean 32 years) and intensity (16 cigarettes per day) for cigarette smoking in their study population.32
However, a later study in Hong Kong observed an increased risk of rectal cancer in current regular smokers (OR=1.4, 95% CI=1.0-2.1), whose average duration of cigarette smoking was 40 years.33
Egyptian smokers in our study reported a mean 25 years of cigarette smoking (SD=15.1 years, range 0.5-66.0 years, median=23.0 years) and smoked 0.9 pack of cigarettes per day on average (SD=0.6 pack, range 0.1-3.0 packs, median=1.0 pack), which were lower than observations in studies showing significant association.31,33
Little is known for smoking water pipes in relation to colorectal carcinoma risk, although water pipe smoking dominates non-cigarette tobacco consumption in Egypt and is emerging in western countries.11,34
Our data suggest that cigarette and non-cigarette smoking have similar impacts on colorectal carcinoma in Egypt.
Colorectal adenomas have been recognized as an important predictor of colorectal carcinoma, but more consistently associated with cigarette smoking across studies.30,35
Synchronous adenomas was only found in 6% of colorectal carcinoma patients in Egypt,5
and the prevalence of polypoid colorectal carcinoma tends to be much lower in Asia and Africa than that in the U.S.2,36
If cigarette smoking acts at the early stage of polypoid colorectal carcinoma, it might be less influential in colorectal carcinogenesis without preceding adenomas.
The excess risk of colorectal carcinoma in female smokers reported in this study should be considered with caution, given the low counts of female smokers present. However, with over half of female patients exposed to passive smoking compared to only 10% of controls and the statistically significant difference between the 2 groups, it might be reasonable to consider that both active and passive smoking have similar biological effect on the etiology of colorectal cancer in this study.
Nevertheless, the difference in gender might reflect uncontrolled confounding factors such as physical activity, social-economical status, and nutrition intake. Additionally, genetic susceptibility may alter risk of colorectal carcinoma in conjunction with gender and residence as we reported earlier.37
Alcohol consumption was less likely to modify our results, because rates of alcohol drinking are very low in Egypt.
Our data also suggest that obesity was significantly associated with colorectal carcinoma in men, but not in women. Similar findings were recently reported in a meta-analysis.38
Excess risks of large bowel cancer in men was found with every 5-unit increase in BMI (RR=1.3, 95% CI=1.3-1.4 for colon cancer; RR=1.1, 95% CI=1.1-1.2 for rectal cancer). In women, higher BMI was only correlated with colon cancer (RR=1.1, 95% CI=1.1-1.2), but not with rectal cancer (RR=1.0, 95% CI=0.99-1.1).38
The major strengths of this study include the relatively large sample size and detailed lifestyle information from a developing country. Although many developing countries have observed a tendency of early onset and a rapid increase in colorectal cancer occurrence,1-3
not many studies were reported from these countries to explore risk factors for colorectal carcinoma. The intense exposure to industrial materials and pesticides, high parity and prolonged lactation in Egypt are distinct from factors seen in most developed countries, providing a unique setting for epidemiological studies. Although food frequency questionnaires and dietary assessments have been criticized in case-control studies,39-40
including dietary assessment could have added knowledge to this study. In summary, this study illustrated the possible role of lifestyle factors in colorectal carcinoma etiology in Egypt. Agricultural and industrial exposures were significantly associated with a higher risk of colorectal carcinoma in this population. In women, parity and breastfeeding were inversely associated with colorectal cancer risk. Future large-scale laboratory studies are needed to assess the dose-response relationship and the actual levels in exposed and non-exposed individuals in this population. Future studies should focus on investigating the biological mechanisms of environmental, industrial, and reproductive factors in colorectal carcinogenesis.