J Gastroenterol DOI 10.1007/s00535-013-0863-5
ORIGINAL ARTICLE—ALIMENTARY TRACT
The relationship between different glycemic statuses and colon polyps in a Taiwanese population Hsin-En Huang • Yi-Ching Yang • Jin-Shang Wu • Ru-Hsueh Wang • Feng-Hwa Lu • Chih-Jen Chang
Received: 20 February 2013 / Accepted: 28 July 2013 Ó Springer Japan 2014
Abstract Background While diabetes is considered as a risk factor for colorectal cancer, there are few studies that address the association between glycemic statuses and different colon polyps, ranging from non-neoplastic polyps to advanced adenomatous polyps. Methods A total of 6,348 participants, consisting of 3,777 men and 2,571 women, with a mean age of 50.5 years, were included for final analysis after excluding subjects with a past history of colorectal cancer, colon polyps/polypectomy, familial adenomatous polyposis, and colorectomy, or missing data. Diabetes and pre-diabetes were defined using the 2011 American Diabetes Association criteria. Subjects were classified into four groups: polypfree, non-neoplastic polyps, non-advanced and advanced adenomatous polyps. Results There were significant differences in the prevalence of diabetes and pre-diabetes among groups with different kinds of colon polyps. In addition, significant differences were also noted in age, total cholesterol, body mass index, triglyceride, high density lipoprotein-cholesterol, fasting plasma glucose, and the prevalence of male gender, hypertension, obesity, current smoking and alcohol drinking among groups. In the multinomial logistic H.-E. Huang Y.-C. Yang J.-S. Wu R.-H. Wang F.-H. Lu (&) C.-J. Chang (&) Department of Family Medicine, National Cheng Kung University Hospital, 138, Sheng Li Road, Tainan 70403, Taiwan, ROC e-mail:
[email protected] C.-J. Chang e-mail:
[email protected] Y.-C. Yang J.-S. Wu F.-H. Lu C.-J. Chang Department of Family Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC
regression analyses, diabetes was related to both nonadvanced and advanced adenomatous polyps, while prediabetes was only related to non-advanced adenomatous polyps. In addition, age C65 years and male gender were associated with both non-advanced and advanced adenomatous polyps, while hypertension and current smoking were independently related to advanced and non-advanced adenomatous polyps, respectively. Conclusions Diabetes, but not pre-diabetes, was associated with a higher risk of advanced adenomatous polyps. In addition, both diabetes and pre-diabetes were important correlates of non-advanced adenomatous polyps. Keywords Non-neoplastic polyps Non-advanced adenomatous polyps Advanced adenomatous polyps Diabetes Pre-diabetes
Introduction Colorectal cancer is one of the most common cancers worldwide [1], and is the third leading cause of cancer death in Taiwan [2]. Colonoscopic polypectomy has been suggested as a preventive action to decrease the incidence of colorectal cancer [3]. Screening colonoscopy is also recommended for the early detection and prevention of colorectal cancer among asymptomatic adults aged 50 or more [4]. According to the histological classification, colorectal polyps mainly consist of non-neoplasia and neoplasia. Non-neoplastic colorectal polyps, including hyperplastic polyps, hamartomas, lymphoid aggregates, or inflammatory polyps, do not have the potential to become malignant [5]. In contrast, neoplastic polyps can become malignant through the adenoma–carcinoma sequence, and these are further divided into non-advanced and advanced
123
J Gastroenterol
adenoma [5, 6]. The former are tubular adenoma (0–25 % villous tissue), while the later include tubulovillous adenoma (25–75 % villous tissue), villous adenoma (75–100 % villous tissue), and adenoma with the following features: a diameter of [ 1 cm, the presence of three or more lesions, or high-grade dysplasia [5, 6]. Diabetes is now considered as a risk factor of cancer in several tissues, including the liver, pancreas, endometrium, breast, colon, and rectum [7]. The possible mechanism underlying the association between diabetes and colorectal cancer is related to hyperinsulinemia, insulin resistance or dysregulation of the insulin-like growth factor (IGF) axis, because insulin may stimulate the cellular proliferation and promote the growth of colorectal cancer cell lines [8, 9]. There are few studies that address the association between diabetes and colonic adenomatous polyps [10–12]. In addition, colonic adenomatous polyps have been shown to be positively associated with metabolic syndrome [13–19] and fasting hyperglycemia [11, 20]. However, most studies did not consider the statuses of colon polyps, from nonneoplastic to advanced adenomatous ones [11–17, 19, 20], and do not clarify the role of pre-diabetes in colon polyps. Therefore, the aim of this study was to evaluate the association between different kinds of colon polyps and glycemic statuses in a Taiwanese population.
Patients and methods We performed a cross-sectional study on 9,435 examinees who underwent health check-ups with colonoscopies at the health examination center of National Cheng Kung University Hospital (NCKUH) between June 2001 and August 2009. Those subjects with a past history of colorectal cancer (n = 42, 0.45 %), colon polyps/polypectomy (n = 352, 3.73 %), familial adenomatous polyposis (n = 1, 0.01 %), and colorectomy (not due to colorectal cancer) (n = 8, 0.08 %), or missing data (any associated variables) (n = 2,685, 28.46 %) were excluded for the study. As a result, 6,348 participants, consisting of 3,777 men and 2,571 women, with an average age of 50.5 years, were included for final analysis. This research was approved by the Institutional Review Board of NCKUH in Taiwan. Before undergoing routine health check-ups, all participants completed a structured questionnaire, including items on basic personal details, medical histories and medication use, and lifestyle factors (cigarette smoking, exercise habits, and alcohol consumption). Each participant then underwent an interview and physical examination performed by a family physician. Anthropometric measurements were made by welltrained staff. An electronic scale (Model HM-586, Jeng Jyi Co. Ltd, Taiwan) was used to measure body weight and
123
height. Body mass index (BMI) was calculated as weight (kilograms) divided by height (meters) squared. A DIANAMP vital signs monitor (Model 1846SX DINAMAP Monitor, Critikon Inc., USA) was used to measure the systolic and diastolic blood pressures (DBPs) of each subject in a supine position after a 5 min rest period in a quiet examination room. We recorded blood pressure from both the right and left arms, and the average of systolic and DBPs was calculated based on this. All the subjects fasted for at least 8 h, and intravenous blood was collected for analysis of fasting glucose, HbA1c, total cholesterol (TC), triglyceride (TG), and high density lipoprotein-cholesterol (HDL-C). Two-hour post-load glucose (2 h-PG) was checked with a 75-g oral glucose tolerance test (OGTT) for all participants, except those who were pregnant or had a past history of diabetes. The fasting glucose was measured by a hexokinase method (Roche Diagnostic GmbH, Mannheim, Germany). The HbA1c was measured by highperformance liquid chromatography (VARIANT II TURBO, Bio-Rad, California, USA). Serum TC, TG and HDL-C levels were determined in the central laboratory of NCKUH with an autoanalyzer (Hitachi 747E, Tokyo, Japan). Obesity was defined as BMI C27 kg/m2 and overweight was defined as 24 kg/m2 B BMI \ 27 kg/m2 [21]. The definition of hypertension was a systolic blood pressure (SBP) C140 mmHg or DBP C90 mmHg, or a positive history of hypertension or receiving antihypertensive treatments according to the Seventh Report of the Joint National Committee. Diabetes mellitus was diagnosed as HbA1c C6.5 %, fasting plasma glucose C126 mg/dL, 2 hPG C200 mg/dL, or those with a past history of diabetes. Pre-diabetes was defined as 5.7 % B HbA1c \ 6.5 %, 100 mg/dL B fasting plasma glucose \ 126 mg/dL, or 140 mg/dL B 2 h-PG \ 200 mg/dL without the above criteria of diabetes. Fasting plasma glucose \126 mg/dL and 2 h-PG \200 mg/dL without diabetes history was categorized as normal glucose tolerance (NGT). Hypertriglyceridemia was TG C150 mg/dL. Current smoking and alcohol drinking were defined as smoking at least 20 cigarettes per month for more than half-a-year and at least once drink per week for more than half-a-year, respectively. Regular exercise was a minimum of 20 min exercise at least three times per week. Before screening colonoscopy, bowel preparation with a standard protocol was carried out with a polyethylene glycol lavage. The colonoscope (CFTYPE Q260AL, OLYMPUS, Japan), operated by an experienced gastroenterologist, was inserted from the anus up to the ileocecal area. We classified colonoscopic findings into four subgroups: polyp-free, non-neoplastic polyps (including hyperplastic polyps, hamartomas, lymphoid aggregates, and non-specific colitis), non-advanced adenomatous
J Gastroenterol
polyps (including low-grade adenoma, such as tubular adenoma), and advanced adenomatous polyps (including adenomatous polyps with one or more features of[1 cm in diameter, high-grade dysplasia, villous histology, and the presence of three or more lesions). In cases with two or more adenomatous polyps, the largest one was measured. Statistical analyses The analyses were performed by using Windows SPSS 17.0 statistical software (Chicago, Illinois, USA), with the data presented as means ± standard deviations or percentages. Univariate analyses included one-way analysis of variance (ANOVA) for the comparison of continuous variables, and Pearson Chi square tests for categorical variables among the groups that had been classified as being polyp-free or having non-neoplastic polyps, nonadvanced adenomatous polyps, and advanced adenomatous polyps. Multinomial logistic regression, a simple extension of logistic regression, is a method to fit multiple logistic regressions on a multi-category unordered response variable that has been dummy coded. Since our dependent variable is a multi-category unordered response, in order to get a number of logit regression estimate for 3 different subgroups of colon polyps as compared to polyp-free subjects, multinomial logistic regression was used to assess the independent association between colon polyps and glycemic statuses, including diabetes, pre-diabetes, and NGT after adjusting age, gender, BMI, hypertension, current smoking, regular exercise, alcohol drinking, hypertriglyceridemia, and TC to HDL-C ratio. A P value \0.05 was considered statistically significant.
Results All the subjects (n = 6,348) were divided into four groups, including polyp-free (n = 5,074), non-neoplastic polyps (n = 590), non-advanced adenomatous polyps (n = 529), and advanced adenomatous polyps (n = 155). Table 1 shows the demographic and clinical parameters for the various groups, and it can be seen that there were significant differences in the prevalence of diabetes and prediabetes among them. In addition, significant differences were also noted in age, gender, TC, BMI, TG, HDL-C, fasting plasma glucose, and the prevalence of hypertension, obesity, current smoking and alcohol drinking. Table 2 shows the odds ratios (OR) and 95 % confidence intervals (CI) for the clinical variables with regard to the risk of non-neoplastic polyps, non-advanced and advanced adenomatous polyps with adjustments for age, gender, hypertension, BMI, glycemic statuses, hypertriglyceridemia, TC to HDL-C ratio, regular exercise, current
smoking and alcohol drinking. Diabetes mellitus was independently related to both non-advanced adenomatous polyps (OR 1.43, 95 % CI 1.10–1.87) and advanced adenomatous polyps (OR 1.63, 95 % CI 1.06–2.51), while prediabetes was only related to non-advanced adenomatous polyps (OR 1.30, 95 % CI 1.05–1.61), but not advanced adenomatous polyps. In addition, advanced adenomatous polyps were associated with age C65 years (OR 2.20, 95 % CI 1.47–3.29), male gender (OR 1.99, 95 % CI 1.31–3.02), and hypertension (OR 1.85, 95 % CI 1.29–2.66), while non-advanced adenomatous polyps were related to age C65 years (OR 1.44, 95 % CI 1.11–1.86), male gender (OR 1.31, 95 % CI 1.05–1.64) and current smoking (OR 1.28, 95 % CI 1.02–1.60). In addition, obesity (OR 1.32, 95 % CI 1.04–1.68), current smoking (OR 1.59, 95 % CI 1.29–1.97), and hypertension (OR 1.32, 95 % CI 1.07–1.63) were the independently associated factors of non-neoplastic polyps. Because some studies showed the relationship between HbA1c and colonic polyposis [22, 23], we changed the variables ‘‘glycemic statuses’’ to ‘‘HbA1c statuses’’ in the multinomial logistic regression. The result showed HbA1c C6.5 %, as compared with HbA1c \5.7 %, was positively associated with advanced and non-advanced adenomatous polyps and nonneoplastic polyps. HbA1c of 5.7–6.49 % was independently related to non-advanced adenomatous polyps and non-neoplastic polyps, but not advanced adenomatous polyps (data not shown).
Discussion The relationship between diabetes/hyperglycemia and colorectal adenomatous polyps is still inconclusive, as some studies show a positive link between them [10–12, 20], while others do not [13–19]. The literature also has inconclusive results with regard to the effect of hyperglycemia on advanced adenomatous polyps [10, 12, 13]. Some studies find that advanced adenomatous polyps are more likely in subjects with diabetes or hyperglycemia, defined as fasting plasma glucose of either C100 or 110 mg/dl [10, 12]. However, these works did not examine the effect of pre-diabetes on adenomatous polyps. Our results reveal that diabetes was independently related to non-advanced and advanced adenomatous polyps. In addition, pre-diabetes was positively associated with non-advanced adenomatous polyps, but not advanced adenomatous polyps. Therefore, the effect of pre-diabetes on the risk of advanced adenomatous polyps was not as strong as that of diabetes, although pre-diabetes increased the risk of nonadvanced adenomatous polyps. In our study, the proportions of subjects with pre-diabetes and diabetes were 25.8 and 13.5 %, respectively. The higher prevalence may be
123
J Gastroenterol Table 1 Comparison of clinical parameters among subjects with polyp-free, non-neoplastic polyps, non-advanced and advanced adenomatous polyps Polyp-free (n = 5,074)
Non-neoplastic polyps (n = 590)
Neoplastic polyps
P value
Non-advanced (n = 529)
Advanced (n = 155) \0.001
Age (year)
49.7 ± 12.1
52.2 ± 11.3
54.6 ± 10.6
56.5 ± 11.4
Male gender (%)
2887 (56.9)
412 (69.8)
361 (68.2)
117 (75.5)
\0.001
Body weight (kg) Waist circumference (cm)
65.2 ± 12.1 83.4 ± 10.2
68.8 ± 11.8 86.6 ± 9.6
67.3 ± 11.7 86.2 ± 9.7
68.9 ± 13.4 87.8 ± 11.5
\0.001 \0.001
Body mass index (kg/m2)
24.4 ± 3.5
25.2 ± 3.3
25.0 ± 3.2
25.5 ± 4.0
\0.001
C27 kg/m2 (%)
1019 (20.1)
155 (26.3)
135 (25.5)
47 (30.3)
24–26.9 kg/m2 (%)
1661 (32.7)
214 (36.3)
190 (35.9)
54 (34.8)
\24 kg/m2 (%)
2394 (47.2)
221 (37.5)
204 (38.6)
54 (34.8)
Hypertension (%)
1062 (20.9)
166 (28.1)
154 (29.1)
65 (41.9)
\0.001
Total cholesterol (mg/dL)
197.2 ± 37.3
201.2 ± 37.7
204.6 ± 39.1
199.0 ± 35.8
\0.001
\0.001
Body mass index statuses
Triglyceride (mg/dL)
128.8 ± 80.8
144.6 ± 84.7
141.8 ± 90.0
148.2 ± 87.2
\0.001
HDL-C (mg/dL)
47.7 ± 13.2
45.5 ± 12.6
46.9 ± 13.3
45.2 ± 13.7
\0.001
Normal glucose tolerance (%)
3152 (62.1)
356 (60.3)
271 (51.2)
75 (48.4)
Pre-diabetes (%)
1295 (25.5)
143 (24.2)
163 (30.8)
39 (25.2)
Diabetes mellitus (%)
\0.001
Glycemic statuses
627 (12.4)
91 (15.4)
95 (18.0)
41 (26.5)
Fasting plasma glucose (mg/dL) Alcohol drinking (%)
89.2 ± 17.8 1091 (21.5)
89.8 ± 14.1 183 (31.0)
92.6 ± 19.6 155 (29.3)
93.5 ± 20.2 44 (28.4)
Regular exercise (%)
637 (12.6)
61 (10.3)
61 (11.5)
18 (11.6)
0.431
Current smoking (%)
1278 (25.2)
237 (40.2)
184 (34.8)
54 (34.8)
\0.001
\0.001 \0.001
Data are expressed as n (%) or mean ± standard deviations HDL-C high density lipoprotein-cholesterol
explained by the following reasons: (1) using 2011 American Diabetes Association diagnostic criteria with additional criteria of HbA1c, (2) more diabetes and impaired glucose tolerance subjects found by OGTT data, (3) absence of repeated fasting plasma glucose and OGTT, 4) higher prevalence of diabetes and pre-diabetes in the Taiwanese population [24, 25]. Insulin resistance is considered as one of the major underlying mechanisms for the link between diabetes/ hyperglycemia and colorectal cancer [8, 9], but few studies directly explore the role of insulin resistance in the association between colorectal adenomatous polyps and diabetes/hyperglycemia [26, 27]. Insulin can directly activate insulin receptors or IGF-1 receptors, which stimulates the proliferation of colonic epithelium through inhibition of apoptosis [8, 9]. In addition to insulin resistance, obesityrelated inflammation and oxidative stress are also hypothesized to play an important role in the carcinogenesis [28, 29]. Some studies show a link between inflammatory cytokines (e.g., CRP) and colorectal neoplasia or adenoma [30, 31]. Inflammatory cytokines can increase oxidative stress, which can stimulate the proliferation of neoplastic
123
colonic cells [29]. All of these processes might partially explain the formation of adenomatous polyps. In our study, the hyperglycemic status in pre-diabetic subjects is less severe than that in diabetic subjects, and the polyps in the former may be less advanced than those in the latter. A possible explanation for this may be related to the shorter duration and lower level of hyperglycemic status, associated dyslipidemia and subsequent oxidative stress in prediabetic subjects [29, 32, 33]. Age is also positively correlated to a higher prevalence of non-advanced or advanced adenomatous polyps in many studies [10, 11, 14–16], and this is also found in the current work. A meta-analysis of screening colonoscopy for an asymptomatic population shows higher maximal detection rates of non-advanced and advanced adenomatous polyps in men than in women [34]. In our study, men also have a higher risk of both non-advanced and advanced adenomatous polyps. The mechanism for this remains unclear, but one possible explanation may be linked to differences in sex hormones [35–37]. Hypertension is another important risk factor for advanced adenomatous polyps in the current study,
J Gastroenterol Table 2 Adjusted odds ratios (OR) and 95 % confidence intervals (CI) of clinical variables on the risk of non-neoplastic polyps, non-advanced and advanced adenomatous polyps based on multinomial logistic regression Variables
Non-neoplastic polyps vs Polyp-free OR (95 % CI)
Non-advanced adenomatous polyps vs Polyp-free OR (95 % CI)
Advanced adenomatous polyps vs Polyp-free OR (95 % CI)
Age, C65 vs \65 years
1.28 (0.98–1.67)
1.44 (1.11–1.86)*
2.20 (1.47–3.29)*
Male vs female
1.24 (1.00–1.54)
1.31 (1.05–1.64)*
1.99 (1.31–3.02)*
Current smoking, yes vs no
1.59 (1.29–1.97)*
1.28 (1.02–1.60)*
1.11 (0.75–1.64)
Alcohol drinking, yes vs no
1.18 (0.95–1.46)
1.20 (0.96–1.51)
1.07 (0.71–1.59)
Regular exercise, no vs yes
1.27 (0.96–1.68)
1.15 (0.86–1.52)
1.17 (0.70–1.93)
Hypertension, yes vs no
1.32 (1.07–1.63)*
1.24 (1.00–1.55)
1.85 (1.29–2.66)*
Body mass index statuses C 27 vs \24 kg/m2
1.32 (1.04–1.68)*
1.26 (0.98–1.62)
1.39 (0.90–2.14)
24–26.9 vs \24 kg/m2
1.21 (0.98–1.48)
1.16 (0.93–1.44)
1.08 (0.73–1.60)
Diabetes mellitus vs NGT
0.94 (0.72–1.22)
1.43 (1.10–1.87)*
1.63 (1.06–2.51)*
Pre-diabetes vs NGT
0.95 (0.63–1.42)
Glycemic statuses 0.82 (0.66–1.02)
1.30 (1.05–1.61)*
Hypertriglyceridemia, yes vs no
1.20 (0.97–1.48)
0.84 (0.67–1.05)
1.27 (0.86–1.87)
TC/HDL-C [ 5, yes vs no
1.09 (0.88–1.34)
1.13 (0.91–1.41)
0.92 (0.62–1.35)
NGT normal glucose tolerance, TC total cholesterol, HDL-C high density lipoprotein-cholesterol * P \ 0.05
although not for non-advanced ones. While one previous study finds a positive association between elevated blood pressure and adenomatous polyps [13], most other works find that hypertension or elevated blood pressure has no association with colorectal adenomatous polyps [11, 14, 16–20]. This discrepancy may be related to subject selection, different classifications of adenomatous polyps, use of anti-hypertensive medications, and different cutoff points for hypertension in these various earlier works. The exact mechanism for the association between hypertension and advanced adenomatous polyps is still unknown, although hypertensive subjects may exhibit hyperinsulinemia status [38, 39], which may result in the formation or progression of colon adenomatous polyps. One meta-analysis provides strong evidence of the detrimental effect of smoking in the formation of colorectal adenoma and its subsequent aggressiveness [40]. However, in the current study smoking was associated with nonneoplastic polyps and non-advanced adenomatous polyps, but not advanced adenomatous polyps. This might be explained by the so-called dilution effect, which means that only a small percentage of non-advanced adenomatous polyps progress to advanced ones [40]. In addition, another explanation might be that smokers quit smoking and changed their lifestyles when their severe colon lesions were first detected in this cross-sectional study. With regard to the association between colorectal adenomatous polyps and alcohol drinking, the previous literature contains inconsistent results [14, 16, 41, 42]. Our study shows no association between alcohol drinking and
colorectal adenomatous polyps, which while consistent with some work [14, 16], contradicts others [41, 42]. This might be explained by the different classifications of colon polyps and definitions of alcohol drinking used in these work. Furthermore, different adjusted variables and the issue of collinearity might also explain these results. Most recent studies do not include physical activity in their multivariate analyses. Although one meta-analysis study shows that physical activity is negatively associated with colorectal adenoma, the results contain significant heterogenicities, and this association becomes statistically insignificant when using the best approach [43]. Our study finds no association between regular exercise and colorectal polyps, and the inconsistent results in the literature suggest that physical activity might be more important in the adenoma to carcinoma sequence than in the development of adenoma [44]. A number of recent studies show a link between metabolic syndrome and colorectal adenomatous polyps [13– 19]. Of the five components of metabolic syndrome, some studies show that dyslipidemia with hypertriglyceridemia and low HDL-C levels are independently associated with an increased the risk of colorectal adenomatous polyps [11, 13, 15, 17, 18, 45], although others find no such relationship [14, 16, 19, 20]. In our study, both TC to HDL-C ratio and TG are not associated in any of the subgroups. In addition, some studies show that central obesity or a higher BMI are associated with colorectal adenomatous polyps [11, 13–19], although this is not found in the current work and an earlier one [20]. One explanation for the insignificant association of adenomatous polyps with
123
J Gastroenterol
hypertriglyceridemia, TC to HDL-C ratio [5, and higher BMI is the collinear effects of hyperinsulinemia, such as diabetes and hypertension. Some limitations in our study affect the interpretation of the results. First, our study adopts a cross-sectional design, and is, thus, not able to draw a causal relationship between different glycemic statuses and colon polyps. Second, we did not record the subjects’ dietary data (e.g., low fat and high fiber diet), and diet might also play an important role in the formation of adenoma. Third, our study was based on a Taiwanese population, and it might not be representative of other ethnic groups. Fourth, we did not repeat the tests of fasting plasma glucose or OGTT, which may result in more cases and proportions of pre-diabetes/diabetes. In addition, nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin may prevent the formation of adenomatous polyps [46–48]. We did not have the records about those medications. However, subjects with diabetes might use aspirin more frequently for preventing cardiovascular diseases or use NSAID for comorbidity than those without. The above possible bias might under-estimate the relationship between diabetes and adenomatous polyps. Thus, the true effect of diabetes on adenomatous polyps may be stronger than the estimation in our study. Finally, since insulin resistance has been suggested as the possible mechanism between glycemic statuses and colon polyps, blood insulin levels and inflammatory markers (e.g., CRP) might be needed for further analysis. In conclusion, diabetes, but not pre-diabetes, was associated with a higher risk of advanced adenomatous polyps in this study. In addition, both diabetes and pre-diabetes were important associated factors of non-advanced adenomatous polyps. Acknowledgments This work was supported by Grant NCKUHFM-101-004 from the Department of Family Medicine, National Cheng-Kung University Hospital. Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108. 2. Bureau of Health Promotion, Department of Health, Taiwan: Taiwan Cancer Registry 2010. http://www.bhp.doh.gov.tw/ BHPnet/English/index.aspx. Accessed 7 Feb 2013. 3. Winawer SJ, Zauber AG, Ho MN, O’Brien MJ, Gottlieb LS, Sternberg SS, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med. 1993;329:1977–81. 4. Lieberman DA, Weiss DG, Bond JH, Ahnen DJ, Garewal H, Chejfec G. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med. 2000;343:162–8.
123
5. Colucci PM, Yale SH, Rall CJ. Colorectal polyps. Clin Med Res. 2003;1:261–2. 6. Thompson PA, Gerner EW. Current concepts in colorectal cancer prevention. Expert Rev Gastroenterol Hepatol. 2009;3:369–82. 7. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33:1674–85. 8. Giouleme O, Diamantidis MD, Katsaros MG. Is diabetes a causal agent for colorectal cancer? Pathophysiological and molecular mechanisms. World J Gastroenterol. 2011;17:444–8. 9. Tsugane S, Inoue M. Insulin resistance and cancer: epidemiological evidence. Cancer Sci. 2010;101:1073–9. 10. Suh S, Kang M, Kim MY, Chung HS, Kim SK, Hur KY, et al. Korean type 2 diabetes patients have multiple adenomatous polyps compared to non-diabetic controls. J Korean Med Sci. 2011;26:1196–200. 11. Hwang ST, Cho YK, Park JH, Kim HJ, Park DI, Sohn CI, et al. Relationship of non-alcoholic fatty liver disease to colorectal adenomatous polyps. J Gastroenterol Hepatol. 2010;25:562–7. 12. Eddi R, Karki A, Shah A, DeBari VA, DePasquale JR. Association of type 2 diabetes and colon adenomas. J Gastrointest Cancer. 2012;43:87–92. 13. Kim BC, Shin A, Hong CW, Sohn DK, Han KS, Ryu KH, et al. Association of colorectal adenoma with components of metabolic syndrome. Cancer Causes Control. 2012;23:727–35. 14. Hu NC, Chen JD, Lin YM, Chang JY, Chen YH. Stepwise relationship between components of metabolic syndrome and risk of colorectal adenoma in a Taiwanese population receiving screening colonoscopy. J Formos Med Assoc. 2011;110:100–8. 15. Wang YY, Lin SY, Lai WA, Liu PH, Sheu WH. Association between adenomas of rectosigmoid colon and metabolic syndrome features in a Chinese population. J Gastroenterol Hepatol. 2005;20:1410–5. 16. Kim JH, Lim YJ, Kim YH, Sung IK, Shim SG, Oh SO, et al. Is metabolic syndrome a risk factor for colorectal adenoma? Cancer Epidemiol Biomarkers Prev. 2007;16:1543–6. 17. Lee GE, Park HS, Yun KE, Jun SH, Kim HK, Cho SI, et al. Association between BMI and metabolic syndrome and adenomatous colonic polyps in Korean men. Obesity (Silver Spring). 2008;16:1434–9. 18. Liu CS, Hsu HS, Li CI, Jan CI, Li TC, Lin WY, et al. Central obesity and atherogenic dyslipidemia in metabolic syndrome are associated with increased risk for colorectal adenoma in a Chinese population. BMC Gastroenterol. 2010;10:51. 19. Morita T, Tabata S, Mineshita M, Mizoue T, Moore MA, Kono S. The metabolic syndrome is associated with increased risk of colorectal adenoma development: the Self-Defense Forces health study. Asian Pac J Cancer Prev. 2005;6:485–9. 20. Tsilidis KK, Brancati FL, Pollak MN, Rifai N, Clipp SL, Hoffman-Bolton J, et al. Metabolic syndrome components and colorectal adenoma in the CLUE II cohort. Cancer Causes Control. 2010;21:1–10. 21. Pan WH, Lee MS, Chuang SY, Lin YC, Fu ML. Obesity pandemic, correlated factors and guidelines to define, screen and manage obesity in Taiwan. Obes Rev. 2008;9(Suppl 1):22–31. 22. Kim BJ, Kim YH, Sinn DH, Kang KJ, Kim JY, Chang DK, et al. Clinical usefulness of glycosylated hemoglobin as a predictor of adenomatous polyps in the colorectum of middle-aged males. Cancer Causes Control. 2010;21:939–44. 23. Tseng PH, Lee YC, Chiu HM, Chen CC, Liao WC, Tu CH, et al. Association of diabetes and HbA1c levels with gastrointestinal manifestations. Diabetes Care. 2012;35:1053–60. 24. Lu FH, Yang YC, Wu JS, Wu CH, Chang CJ. A population-based study of the prevalence and associated factors of diabetes mellitus in southern Taiwan. Diabet Med. 1998;15:564–72.
J Gastroenterol 25. Hung HC, Yang YC, Ou HY, Wu JS, Lu FH, Chang CJ. The relationship between impaired fasting glucose and self-reported sleep quality in a Chinese population. Clin Endocrinol. 2013;78:518–24. 26. Schoen RE, Weissfeld JL, Kuller LH, Thaete FL, Evans RW, Hayes RB, et al. Insulin-like growth factor-I and insulin are associated with the presence and advancement of adenomatous polyps. Gastroenterology. 2005;129:464–75. 27. Yoshida I, Suzuki A, Valle´e M, Matano Y, Masunaga T, Zenda T, et al. Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in the proximal colon. Clin Gastroenterol Hepatol. 2006;4:1225–31. 28. Giovannucci E. Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr. 2007;86:S836–42. 29. Cowey S, Hardy RW. The metabolic syndrome: a high-risk state for cancer? Am J Pathol. 2006;169:1505–22. 30. Chiu HM, Lin JT, Chen TH, Lee YC, Chiu YH, Liang JT, et al. Elevation of C-reactive protein level is associated with synchronous and advanced colorectal neoplasm in men. Am J Gastroenterol. 2008;103:2317–25. 31. Otake T, Uezono K, Takahashi R, Fukumoto J, Tabata S, Abe H, et al. C-reactive protein and colorectal adenomas: Self Defense Forces Health Study. Cancer Sci. 2009;100:709–14. 32. Delmas-Beauvieux MC, Peuchant E, Thomas MJ, Dubourg L, Pinto AP, Clerc M, et al. The place of electron spin resonance methods in the detection of oxidative stress in type 2 diabetes with poor glycemic control. Clin Biochem. 1998;31:221–8. 33. Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis. Diabetes Care. 1992;15:815–9. 34. Niv Y, Hazazi R, Levi Z, Fraser G. Screening colonoscopy for asymptomatic population; a meta-analysis. Dig Dis Sci. 2008;53:3049–55. 35. Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, Hubbell FA, Ascensao J, Rodabough RJ, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med. 2004;350:991–1004. 36. Kennelly R, Kavanagh DO, Hogan AM, Winter DC. Oestrogen and the colon: potential mechanisms for cancer prevention. Lancet Oncol. 2008;9:385–91.
37. Grodstein F, Martinez ME, Platz EA, Giovannucci E, Colditz GA, Kautzky M, et al. Postmenopausal hormone use and risk for colorectal cancer and adenoma. Ann Intern Med. 1998;128:705–12. 38. Salonen JT, Lakka TA, Lakka HM, Valkonen VP, Everson SA, Kaplan GA. Hyperinsulinemia is associated with the incidence of hypertension and dyslipidemia in middle-aged men. Diabetes. 1998;47:270–5. 39. Reaven GM, Lithell H, Landsberg L. Hypertension and associated metabolic abnormalities–the role of insulin resistance and the sympathoadrenal system. N Engl J Med. 1996;334:374–81. 40. Botteri E, Iodice S, Raimondi S, Maisonneuve P, Lowenfels AB. Cigarette smoking and adenomatous polyps: a meta-analysis. Gastroenterology. 2008;134:388–95. 41. Terry MB, Neugut AI, Bostick RM, Sandler RS, Haile RW, Jacobson JS, et al. Risk factors for advanced colorectal adenomas: a pooled analysis. Cancer Epidemiol Biomarkers Prev. 2002;11:622–9. 42. Martinez ME, McPherson RS, Annegers JF, Levin B. Cigarette smoking and alcohol consumption as risk factors for colorectal adenomatous polyps. J Natl Cancer Inst. 1995;87:274–9. 43. Wolin KY, Yan Y, Colditz GA. Physical activity and risk of colon adenoma: a meta-analysis. Br J Cancer. 2011;104:882–5. 44. Colbert LH, Lanza E, Ballard-Barbash R, Slattery ML, Tangrea JA, Caan B, et al. Adenomatous polyp recurrence and physical activity in the Polyp Prevention Trial (United States). Cancer Causes Control. 2002;13:445–53. 45. Sun ZJ, Huang YH, Wu JS, Yang YC, Chang YF, Lu FH, et al. The association of serum lipids with the histological pattern of rectosigmoid adenoma in Taiwanese adults. BMC Gastroenterol. 2011;11:54. 46. Arber N, Eagle CJ, Spicak J, Ra´cz I, Dite P, Hajer J, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006;355:873–84. 47. Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med. 2003;348:883–90. 48. Edwards TL, Shrubsole MJ, Cai Q, Li G, Dai Q, Rex DK, et al. A study of prostaglandin pathway genes and interactions with current nonsteroidal anti-inflammatory drug use in colorectal adenoma. Cancer Prev Res. 2012;5:855–63.
123
