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Body Mass Index as a Predictor of Advanced Colorectal Neoplasia

Background: Colorectal cancer (CRC) is the third frequent cancer in Korea. There are several risk factors including male sex, older age, smoking and family history of colon cancer. Recently, obesity is thought to be a risk factor for CRC and advanced colon polyps. Therefore, we designed a cross-sectional study to determine the association between BMI and advanced colorectal neoplasia. Methods: A total of 256 patients with advanced colorectal neoplasia who were diagnosed using colonoscopy between May, 2004 and December, 2011 were included in this study. Advanced colorectal neoplasia was defined large (≥1 cm) adenoma or adenocarcinoma. We compared these patients to a control group consisting of 217 subjects with normal colonoscopic findings recruited during the same period. Results: Of the 256 patients, there were 132 (51.6%) men, and the mean age was 56.4±12.3 years. The rate of males, alcohol drinker and current smokers was significantly higher in the advanced colorectal neoplasia compared to control group. In the subgroup analysis, the mean age and body mass index (BMI, kg/m2) of advanced colorectal neoplasia were higher than control group in the female subjects. However, there were no significant differences between two groups in the male subjects. Multiple logistic regression analysis identified overweight (BMI 23.0–24.9 kg/m2, odds ratios [OR]=2.022) and obesity (BMI≥25 kg/m2, OR=2.383) as independent risk factors for advanced colorectal neoplasia. Conclusions: We suggest that BMI should be considered as an independent risk factor for advanced colorectal neoplasia, and people with high BMI should be recommended to undergo colonocoscopy screening earlier than scheduled.


INTRODUCTION
According to the Korean Central Cancer Registry, the prevalence of colorectal cancer (CRC) was 25,860 (12.8%), placing itself as the third frequent cancer in 2010. 1 This data showed that colon cancer was diagnosed in 62.5 and 40.8 per 100,000 of men and women, respectively. CRC has become a second and third cancer in men and women.
In addition, this rate has shown a significant increase since 1999, compared with other cancers such as stomach cancer (men: -0.5%, women: -0.4%) and hepatocellular carcinoma (men: -2.1%, women: -1.6%). 2,3 Western diet, life style and increased obesity are suggested as causes of increased CRC prevalence. Risk factors such as alcohol intake, smoking, low fiber-high lipid diet, high consumption of red meat, low level of physical activity and obesity have been suggested in many studies. 4,5 Recently, obesity has become a major concern as a risk factor for CRC. were enrolled in this cross-sectional study. One hundred and fifty-eight subjects with colorectal adenoma larger than 1 cm and 98 subjects with CRC were included in this study. Two hundred and seventeen subjects who had normal screening colonoscopic findings without colorectal adenoma or cancer in the same period were enrolled as a control group.

Data collection
We reviewed the participants' age, gender, smoking habits and alcohol intake from their medical records. Current smoker was defined as a subject who had been smoking at least one cigarette per day for the previous 12 months and an ex-smoker was defined as a subject who had ceased smoking at least 12 months before enrollment and a never smoker was defined as a subject who had never smoked before. Alcohol consumption was defined as drinking over

Statistical analysis
We analyzed three groups; advanced adenoma group, CRC group and control groups. One-way ANOVA analysis was selected to compare age, height, body weight and BMI among the three groups; chi-squared analysis was used to determine the significances of differences in sex, alcohol intake and smoking among the three groups. Binary logistic regression analysis was used to determine whether BMI was an independent risk factor for advanced colorectal neoplasia after adjusting for age, sex, smoking and alcohol intake. Statistical analysis was obtained by SPSS for 19.0

Clinical characteristics of subjects according to gender
In the gender subgroup analysis, there were no significant differences in BMI between the control group and advanced colorectal neoplasia group in male subjects (Table   2). However, BMI of advanced colorectal neoplasia group was significantly higher than that of control group in female subjects (Table 2). BMI was also significantly different among advanced adenoma, CRC and control groups in female, but was not a significant difference among three groups in male.

Risk factors for advanced colorectal neoplasia
Mutivariate logistic analysis identified age, female gender, current smoking and BMI as independent risk factors for colorectal adenoma and carcinoma ( increased incidence of both colon and rectal cancer in men, and a 9% higher incidence of colon cancer in women. 4 Okabayashi et al. 9 suggested that increasing BMI is associated with an increased risk of colorectal adenoma. 2.00-9.11). There was no such relationship in the male population. These results suggest the hypothesis that BMI is a significant risk factor for colorectal adenoma in females. In this study, we showed that BMI is related with the prevalence of colorectal neoplasia in the female group (Table 3). This result is similar to a previous study. 14 However, another study demonstrated that there were no significant differences in adenoma prevalence between sexes. 9 Pre-menopausal females had a higher risk of adenoma (OR=2.48; 95% CI=0.56-11.05) when compared with post-menopausal females (OR=1.06; 95% CI=0.77-1.45). 9,15 However, men have been shown to have a higher association between BMI and CRC compared to women, although the findings of this meta-analysis did not de-monstrate any significance of male gender in colorectal adenoma formation in relation to BMI. 9,16 BMI is a definite risk factor for colorectal cancer and has a major role in pre-cancer stage. There are several hypotheses regarding the development of colon cancer and obesity. 17 Patients with insulin resistance are able to have chronic hyperinsulinemia and increased Insulin-like growth factor (IGF) to inhibit the synthesis of Insulin-like growth factor binding protein. 18 Therefore, insulin and IGF-1 are thought to be risk factors for colon cancer.
Leptin, which is a kind of hormone called adipokine in adipose tissues, is also associated with colon cancer. 19 23 We also suggest that current smoking is significantly associated with advanced ade-noma and CRC.
The current study has some potential limitations. The data of weight and height were collected from patient selfreport. Moreover, regarding the history of smoking and alcohol consumption habits, we did not clearly define the amount of alcohol consumption amount and smoking in this study. Furthermore, we did not include other factors such as past medical illnesses, diet, physical activity, NSAIDs use and family medical history.
In spite of these limitations, we revealed that BMI had a correlation with the prevalence of advanced colorectal neoplsia, and was an independent risk factor for advanced colorectal neoplasia along with other factors such as age, male gender, and smoking.
Although this study involved a small population, we revealed a positive association between BMI and colorectal adenoma and CRC. In addition, the prevalence of advanced colorectal neoplasia is significantly higher in female gender and current smokers, and this prevalence increases with age. However, further studies are needed to clarify how obesity affects colorectal neoplasia development.