Colorectal Cancer In Men Research Articles

Mismatch Repair mRNA and Protein Expression in Intestinal Adenocarcinoma in Sika Deer (Cervus nippon) Resembling Heritable Non-polyposis Colorectal Cancer in Man

Intestinal adenocarcinomas seen in an inbred herd of farmed sika deer (Cervus nippon) morphologically resembled human hereditary non-polyposis colorectal cancer (HNPCC). Features common to both included multiple de novo sites of tumourigenesis in the proximal colon, sessile and non-polyposis mucosal changes, the frequent finding of mucinous type adenocarcinoma, lymphocyte infiltration into the neoplastic tubules and Crohn's-like lymphoid follicles at the deep margin of the tumour. HNPCC is defined by a germline mutation of mismatch repair (MMR) genes resulting in their inactivation and loss of expression. To test the hypothesis that similar MMR gene inactivation occurs in the deer tumours, the expression of the four most important MMR genes, MSH2, MLH1, MSH6 and PMS2, was examined at the mRNA level by reverse transcriptase polymerase chain reaction (n = 12) and at the protein level by immunohistochemistry (n = 40) in tumour and control tissues. All four genes were expressed equally in normal and neoplastic tissues, so MMR gene inactivation could not be implicated in the carcinogenesis of this tumour in sika deer.

Ocena zagrożenia rakiem jelita grubego w Polsce na podstawie analizy współczynników epidemiologicznych

Malignant tumours are one of the leading causes of death, as well as one of the most important health problems, in Poland and worldwide. Aim of the research was to assess the risk of colorectal cancer in a population of men and women in Poland based on the analysis of data from the most recent studies and epidemiological sources, particularly from the National Cancer Registry. In this study, epidemiological indicators of incidence and deaths for general colorectal cancer (ICD-10: C18–C21) as well as for particular cancer locations (C18 – colon, C19 – rectosigmoid junction, C20 – rectum, C21 – anus and anal canal) analized in men and women in Poland in 2011 as well as the profile of these parameters in years 1999–2011. The incidence for colorectal cancer (CRC) in man: structure indicators (SI) – 12.4%, age standardized rates (ASR) – 30.2/105; in women: SI – 10.0%, ASR – 18.0/105. The deaths due to CRC in men: SI – 11.4%, ASR – 19.8/105; in women: SI – 11.8%, ASR – 10.2/105. Colorectal cancer is a serious threat to the health of Poles, characterised by its dynamics increasing with population age, by high incidence and mortality, as well as by a persistent, constant tendency for increasing epidemiological rates, especially among men. The differentiation of epidemiological rates follows from tumour location. Higher incidence and mortality rates are registered for the population of men and among the residents of Western Poland.

Omega-3 polyunsaturated fatty acids and non-communicable diseases: meta-analysis based systematic review.

The aim of this updated systematic review is to summarize the evidence of the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on non-communicable diseases (NCDs). Publications of meta-analysis up to August 2014 were systematically searched from PubMed, the Cochrane and EMBASE databases. N-3 PUFAs have the following beneficial effects; cardio-protective effects, reduce ischemic stroke risk in both men and women and total stroke risk in women, increase insulin sensitivity in Asians, decrease risk of breast cancer and colorectal cancer in men. However, n-3 PUFAs may have unfavourable effects on type 2 diabetes in Caucasians. In conclusion, n-3 PUFA plays a crucial role in the prevention of NCDs, however, unfavourable effects should be considered in subjects with certain clinical conditions. Cross-cultural studies on the effect of n-3 PUFA on type 2 diabetes are needed to verify why diabetic patients with different ancestries have a different response to n-3 PUFA.

Abstract 2176: Obesity and risk of colorectal cancer: A Mendelian randomization study

Abstract Background: Obesity has been consistently linked to higher risk of colorectal cancer (CRC) in men, whereas the association is generally lower in women. Although these findings come from well conducted epidemiologic studies, it is difficult to exclude all other explanations for associations in observational studies, such as measurement error and other forms of bias, reverse causality and confounding. Mendelian randomization studies, using instrumental variables (IVs), can overcome some of the inherent limitations of observational studies and provide an unbiased and unconfounded estimate of the causal association between an exposure and outcome. Objective: We used genetic variants that are associated with body mass index (BMI) or waist-hip ratio (WHR) to examine the causal association between obesity and CRC. Methods: We used epidemiologic and genetic data from 10 226 CRC cases and 10 286 controls of European ancestry from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) or the Colon Cancer Family Registry (CCFR). The primary Mendelian randomization analysis was performed using a genetic risk score, derived from 77 established “BMI-increasing” genetic variants, as an instrumental variable for higher BMI. We additionally derived a risk score for WHR using 47 variants for WHR. We compared the IV odds ratio (OR) with the OR obtained using a traditional multivariable logistic regression model adjusted for age, sex, smoking status, family history, aspirin use, and HRT use (women). Results: For men and women combined, in traditional multivariable analysis, each 5 kg/m2 increase in BMI was associated with a 24% (95% confidence interval [CI]: 1.17-1.32) increase in risk of CRC. In the IV analysis, the OR was higher (IV-OR per 5 kg/m2=1.54, 95% CI: 1.15-2.06); however, the two estimates were not statistically significantly different (Pdifference=0.07). For men, there was a statistically significant association between BMI and CRC in traditional multivariable analysis (OR per 5kg/m2=1.33, 95% CI: 1.21-1.46), but no association in the IV analysis (IV-OR per 5 kg/m2=1.13, 95% CI: 0.70-1.83). The estimates however were not significantly different (Pdifference=0.56). In contrast, for women, the IV estimate (IV-OR per 5 kg/m2=1.94, 95% CI: 1.33-2.82) was significantly higher than the estimate from the traditional multivariable analysis (OR per 5 kg/m2=1.18, 95% CI: 1.11-1.25; Pdifference=0.01). In secondary analysis, we found a positive association between WHR and CRC in men (IV-OR per 0.1 unit increase=1.84, 95% CI: 1.02-3.31) but no statistically significant association in women (IV-OR per 0.1 unit increase=1.22, 95% CI: 0.75-1.98). Conclusions: Obesity is independently associated with risk of CRC and may confer greater risk of CRC in women than previously reported. The mechanisms remain largely unknown; however these results suggest that visceral abdominal fat may be particularly important for promoting CRC in men. Citation Format: Aaron P. Thrift, Sonja I. Berndt, Andrew T. Chan, Jenny Chang-Claude, Martha L. Slattery, Michelle Cotterchio, Graham Casey, John D. Potter, Polly A. Newcomb, Emily White, Hermann Brenner, Ulrike Peters, Peter T. Campbell. Obesity and risk of colorectal cancer: A Mendelian randomization study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2176. doi:10.1158/1538-7445.AM2014-2176

Excess body weight and cancer risk in patients with type 2 diabetes who were registered in Swedish National Diabetes Register--register-based cohort study in Sweden.

AimTo assess the association between excess body weight and cancer risk in patients with type 2 diabetes (T2D) who were registered in the Swedish National Diabetes Register (NDR).MethodsThis is a cohort study based on 25,268 patients with T2D and baseline BMI≥18.5 kg/m2 from NDR 1997–1999. Subjects were grouped according to BMI into normal weight (18.5 to 24.9), overweight (25 to 29.9) or obesity (30 or more). All subjects were followed until the first occurrence of cancer, or death, or the end of follow-up (December 31, 2009). Adjusted hazard ratios (HRs) and 95% confidence interval (CI) for cancer risks were estimated by Cox regression.ResultsIn men with T2D, overweight was associated with increased risks of all cancer [1.13 (1.02–1.27)], gastrointestinal cancer [1.34 (1.07–1.72)] and colorectal cancer [1.59 (1.18–2.13)]; obesity was related to higher risks of all cancer [1.17 (1.04–1.33)], gastrointestinal cancer [1.40 (1.08–1.82)] and colorectal cancer [1.62 (1.17–2.24)]. In women with T2D, obesity was associated with increased risk of all cancer [1.30 (1.12–1.51)], gastrointestinal cancer [1.40 (1.03–1.91)] and postmenopausal breast cancer [1.39 (1.00–1.91)].ConclusionsExcess body weight was associated with increased risks of all cancer, gastrointestinal cancer and colorectal cancer in men with T2D. Obesity was related with elevated risks of all cancer, gestational cancer and postmenopausal breast cancer in women with T2D.

Patterns of Community-Based Opioid Prescriptions in People Dying of Cancer

ContextStudies of opioid use in cancer patients have been cross-sectional or have focused on mean consumption over a specific time interval. ObjectivesThis study aimed to determine the temporal pattern of prescribed opioids at a population level. MethodsUsing Quebec administrative databases, we ascertained details of cancer-related deaths and filled community-based opioid prescriptions (COPs) in 48,420 decedents from 2003 to 2006. ResultsUsing group-based trajectory modeling, based on when people started to fill COPs, our population-based study demonstrated patterns of filled COPs with six distinct trajectories. An earlier start in opioid consumption resulted in a higher group average morphine daily dose; those who were already filling COPs at study entry (5.2%) had a final dose of more than 300mg by the time of death. Remarkably, 58.8% of people had not filled COPs with a biweekly average greater than 1mg earlier than two weeks before death, marking the end of follow-up. Breast cancer in women, prostate or colorectal cancer in men, and younger age and multiple myeloma in both sexes were positively associated with earlier filling of COPs. ConclusionPatients dying of cancer require increasing doses of opioids over time; although we cannot distinguish the relative contributions of disease progression and opioid tolerance, age and certain cancers seem related to this phenomenon. Given the potentially prohibitive cost of prospective epidemiological studies, more elaborate clinical administrative databases that include regular pain assessment are necessary to determine optimal opioid use and factors associated with dose increases over time at a population level.

Associations of anthropometric factors with KRAS and BRAF mutation status of primary colorectal cancer in men and women: a cohort study.

Obesity is a well-established risk factor for colorectal cancer (CRC), and accumulating evidence suggests a differential influence of sex and anthropometric factors on the molecular carcinogenesis of the disease. The aim of the present study was to investigate the relationship between height, weight, bodyfat percentage, waist- and hip circumference, waist-hip ratio (WHR), body mass index (BMI) and CRC risk according to KRAS and BRAF mutation status of the tumours, with particular reference to potential sex differences. KRAS and BRAF mutations were analysed by pyrosequencing in tumours from 494 incident CRC cases in the Malmö Diet and Cancer Study. Hazard ratios of CRC risk according to anthropometric factors and mutation status were calculated using multivariate Cox regression models. While all anthropometric measures except height were associated with an increased risk of KRAS-mutated tumours, only BMI was associated with an increased risk of KRAS wild type tumours overall. High weight, hip, waist, WHR and BMI were associated with an increased risk of BRAF wild type tumours, but none of the anthropometric factors were associated with risk of BRAF-mutated CRC, neither in the overall nor in the sex-stratified analysis. In men, several anthropometric measures were associated with both KRAS-mutated and KRAS wild type tumours. In women, only a high WHR was significantly associated with an increased risk of KRAS-mutated CRC. A significant interaction was found between sex and BMI with respect to risk of KRAS-mutated tumours. In men, all anthropometric factors except height were associated with an increased risk of BRAF wild type tumours, whereas in women, only bodyfat percentage was associated with an increased risk of BRAF wild type tumours. The results from this prospective cohort study further support an influence of sex and lifestyle factors on different pathways of colorectal carcinogenesis, defined by KRAS and BRAF mutation status of the tumours.

Dietary intake of fish, ω‐3 and ω‐6 fatty acids and risk of colorectal cancer: A prospective study in U.S. men and women

The association between fish, ω-3 and ω-6 polyunsaturated fatty acid (PUFA) intake and risk of colorectal cancer (CRC) remains inconclusive. Recent prospective studies suggest that the relationship may vary by gender, subsite and duration of follow-up. We followed 123,529 US adults (76,386 women and 47,143 men) without a history of cancer at baseline for 24 to 26 years. Fish and PUFA intake was assessed at baseline and updated every 4 years by using a validated food-frequency questionnaire. We found no overall association between fish, ω-3 and ω-6 PUFA intake and CRC risk with hazard ratio (HR) of 1.03 [95% confidence interval (CI): 0.89-1.20] comparing marine ω-3 intake of ≥ 0.30 g/d versus <0.15 g/d among women and 1.05 (95% CI: 0.85-1.30) comparing intake of ≥ 0.41 g/d versus <0.16 g/d among men. However, fish and marine ω-3 PUFA intake appeared to be positively associated with risk of distal colon cancer in both men and women and inversely with risk of rectal cancer in men. In an analysis based on a limited number of cases, marine ω-3 PUFA intake assessed 12-16 years before diagnosis tended to be inversely associated with CRC risk in men (HR: 0.76; 95% CI: 0.52-1.10). In conclusion, although no overall association between fish, ω-3 or ω-6 PUFA intake was observed with CRC risk, marine ω-3 PUFA may be differentially associated with risk of distal colon and rectal cancers and a long latency may be needed for its protection against CRC in men.

Integrating men's health and masculinity theories to explain colorectal cancer screening behavior.

Colorectal cancer (CRC) is the third most common cause of cancer deaths among men in the United States. Although CRC screening has been found to reduce CRC incidence and mortality, current screening rates among men are suboptimal due to various practical and psychosocial barriers. One potential barrier to CRC screening identified in qualitative studies with men is the threat to masculinity that endoscopic screening methods pose. Indeed, beliefs about masculinity have been predictive of other preventive health behaviors among men. In this review article, we propose a novel conceptual framework to explain men's CRC screening behavior that integrates masculinity norms, gender role conflict, men's health care experiences, behaviors, and beliefs, and social and background variables. This framework has the potential to guide future research on men's CRC screening behaviors and other health behaviors and may inform gender-sensitive interventions that target masculinity beliefs to increase preventive health behaviors.

Cardiorespiratory fitness and risk of cancer incidence and cause-specific mortality following a cancer diagnosis in men: The Cooper Center longitudinal study.

1520 Background: Few studies have examined the prognostic importance of cardiorespiratory fitness (CRF) to predict cancer incidence or cause-specific mortality following a cancer diagnosis in men. Accordingly, we examined the relationships between baseline CRF and incidence of prostate, lung, or colorectal cancer in men at Medicare age and subsequent cause-specific mortality among men diagnosed with cancer. Methods: The Cooper Center Longitudinal Study (CCLS) is a prospective observational cohort study of participants undergoing a preventive health examination including CRF assessment at the Cooper Clinic in Dallas, Texas. We studied 17,049 men with a complete CCLS medical exam and cardiovascular risk factor assessment at a mean age of 50± 9 years. Cancer incidence was defined using Medicare claims data. Cox proportional models were used to estimate the risk of adjusted primary cancer incidence and cause-specific mortality after cancer according to baseline age-specific CRF quintiles (Q). Results: The mean times from CRF assessment to cancer incidence and death were 20.2 ± 8.2 years and 24.4 ± 8.5 years, respectively. During this period, 2885 men were diagnosed with prostate, lung, or colorectal cancer and 769 died. Compared with men in lowest CRF quintile, the adjusted hazard ratio (HR) for incident lung, colorectal, and prostate cancer incidence among men in the highest CRF quintile was 0.32 (95% CI: 0.20 to 0.51, p&lt;0.001), 0.62 (95% CI: 0.40 to 0.97, p=0.05), 1.13 (95% CI: 0.97 to 1.33, p=0.14), respectively. In men developing cancer, both cancer-specific mortality and cardiovascular-specific mortality declined across increasing CRF quintiles (p’s &lt;0.001). A 1-MET increase in CRF was associated with a 14% reduction in cancer-specific mortality (HR 0.86, 95% CI: 0.81-0.91, p&lt;0.001), and 23% reduction in cardiovascular-specific mortality (HR 0.77, 95% CI: 0.69-0.85, p&lt;0.001). Conclusions: Fitness is a strong independent predictor of incident lung and colorectal cancer and remained a robust predictor of cause-specific mortality in middle-aged and older men diagnosed with lung, prostate, or colorectal cancer.

Estimates of cancer burden in Abruzzo and Molise

Abruzzo and Molise are two regions located in the south of Italy, currently without population-based cancer registries. The aim of this paper is to provide estimates of cancer incidence, mortality and prevalence for the Abruzzo and Molise regions combined. The MIAMOD method, a back-calculation approach to estimate and project the incidence of chronic diseases from mortality and patient survival, was used for the estimation of incidence and prevalence by calendar year (from 1970 to 2015) and age (from 0 to 99). The survival estimates are based on cancer registry data of southern Italy. The most frequently diagnosed cancers were those of the colon and rectum, breast and prostate, with 1,394, 1,341 and 698 new diagnosed cases, respectively, estimated in 2012. Incidence rates were estimated to increase constantly for female breast cancer, colorectal cancer in men and melanoma in both sexes. For prostate cancer and male lung cancer, the incidence rates increased, reaching a peak, and then decreased. In women the incidence of colorectal and lung cancer stabilized after an initial increase. For stomach and cervical cancers, the incidence rates showed a constant decrease. Prevalence was increasing for all the considered cancer sites with the exception of the cervix uteri. The highest prevalence values were estimated for breast and colorectal cancer with about 12,300 and over 8,200 cases in 2012, respectively. In the 2000s the mortality rates declined for all cancers except skin melanoma and female lung cancer, for which the mortality was almost stable. This paper provides a description of the burden of the major cancers in Abruzzo and Molise until 2015. The increase in cancer survival, added to population aging, will inflate the cancer prevalence. In order to better evaluate the cancer burden in the two regions, it would be important to implement cancer registration.

Estimates of cancer burden in Puglia

A regional population-based cancer registry that provides incidence and survival data has become active only recently. Since it is important to know the time trends of basic epidemiological indicators to understand the cancer burden in the region, this paper will provide incidence, prevalence and mortality estimates in the region for seven major cancers for the period 1970-2015. The estimates were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Survival was modeled on the basis of published data from the Italian cancer registries. The incidence rates are estimated to be still increasing for female breast cancer, colorectal cancer in men and skin melanoma in both sexes. By contrast, the incidence rates indicate a decreasing trend for cervix uteri cancer and stomach cancer, the latter both in men and women. For these cancers an analogous trend is observed for mortality, confirming the reduction of the risk factors related to these cancer types. The incidence rates for lung cancer and prostate cancer in men were estimated to rise, reach a peak, and then decrease in the last part of the considered period. Prevalence increased for all the considered cancers except cervix cancer. The increase was striking for breast cancer and less pronounced for stomach cancer in both genders. This paper provides a description of the burden of the major cancers until 2015. The results highlight the need to reinforce effective preventive measures to contrast cancers related to an unhealthy lifestyle and to increase the compliance with organized screening programs to reduce the colorectal and breast cancer burden.

A prospective study of plasma inflammatory markers and risk of colorectal cancer in men

Background:Chronic inflammation may mediate risk of colorectal cancer (CRC); however, the association between circulating inflammatory markers and risk of CRC has been inconsistent.Methods:We prospectively evaluated the association of plasma C-reactive protein (CRP), interleukin-6 (IL-6), and the soluble tumour necrosis factor receptor 2 (sTNFR-2) with incident CRC among 274 cases and 532 matched controls nested in the Health Professionals Follow-up Study.Results:Multivariate relative risk (RR) of CRC comparing the extreme quartiles of plasma IL-6 was 1.54 (95% confidence interval (CI), 0.99–2.40; Ptrend=0.02). However, after excluding cases diagnosed within 2 years of blood draw, this association was not statistically significant (RR=1.26, 95% CI, 0.78–2.05; Ptrend=0.21). In analyses restricted to cases diagnosed at least 2 years after blood draw, the association of IL-6 with CRC appeared to differ by body mass index such that the significantly positive association was only present among lean individuals (Pinteraction=0.03). We did not observe any significant association between CRP or sTNFR-2 and CRC.Conclusion:Plasma inflammatory markers are not generally associated with risk of CRC among men. However, the possibility that plasma IL-6 is associated with increased risk of CRC among lean men requires further investigation.

Abstract 103: A prospective study of plasma inflammatory markers and risk of colorectal cancer in men.

Abstract Chronic inflammation may mediate risk of colorectal cancer (CRC); however, the association between circulating inflammatory markers and risk of CRC has been inconsistent. We prospectively evaluated the association of plasma C-reactive protein (CRP), interleukin-6 (IL-6), and the soluble tumor necrosis factor receptor 2 (sTNFR-2) with incident CRC among 18,225 men in the Health Professionals Follow-up Study who provided blood samples in 1994. Through 2008, we documented 274 CRC cases and matched up to 2 controls by age and date of blood draw. We used conditional logistic regression to estimate relative risks (RRs) and confidence intervals (CIs). Compared to men in the lowest quartile of plasma IL-6 (Q1), men in the highest quartile (Q4) had a multivariate RR for CRC of 1.54 (95% CI, 0.99-2.40; Ptrend = .02). However, after excluding cases diagnosed within 2 years of blood draw, the association was substantially attenuated (Q4 versus Q1, RR = 1.26, 95% CI = 0.78-2.05; Ptrend = .21). In analyses restricted to cases diagnosed at least 2 years after blood draw, the association of IL-6 with CRC appeared to differ by body mass index such that the significantly positive association was only present among lean individuals (Pinteraction = .03). We did not observe any significant association between CRP or sTNFR-2 and CRC. Taken together, plasma inflammatory markers are not generally associated with risk of CRC among men. However, the possibility that plasma IL-6 is associated with increased risk of CRC among lean men requires further investigation. Citation Format: Mingyang Song, Kana Wu, Shuji Ogino, Charles S. Fuchs, Edward L. Giovannucci, Andrew T. Chan. A prospective study of plasma inflammatory markers and risk of colorectal cancer in men. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 103. doi:10.1158/1538-7445.AM2013-103

Abstract 4820: Habitual intake of total flavonoids and flavonoid subclasses and risk of colorectal cancer in men and women.

Abstract Background: Flavonoids inhibit the growth of colon cancer cells in vitro. In a recent randomized controlled trial, the Polyp Prevention Trial, a higher intake of one sub-class, flavonols, was significantly associated with a 76% reduced risk of recurrent advanced adenoma. Cohort studies that have examined the association between flavonoid intake and risk of colorectal cancer (CRC) have yielded inconsistent results, but most previous studies only evaluated habitual intake of a limited number of subclasses and there is growing evidence for differential effects depending on subtle difference in structure between the sub-classes Objective: To examine whether higher habitual dietary intake of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones and polymers) are associated with lower risk of CRC. Methods: Using data from validated food frequency questionnaires administered every four years and an updated USDA flavonoid food composition database flavonoid intakes were calculated for 73,666 participants from the Nurses’ Health Study I, and for 32,059 participants from the Health Professionals Follow-up Study. Results: During 16 years of follow-up, 1,405 colorectal cancer cases (652 in men, 753 in women) were identified. Intakes of total flavonoids and subclasses were not associated with risk of CRC (hazard ratios (95% confidence interval) multivariable adjusted for age, smoking before age 30, family history of colorectal cancer, history of endoscopy, aspirin use, body mass index, physical activity, postmenopausal hormone use in women, alcohol consumption, intake of total energy, calcium and vitamin D; highest vs. lowest quintile: total flavonoids, men: 0.97 (0.75-1.26), women: 1.00 (0.80-1.26); flavonols, men: 0.98 (0.76-1.26), women: 1.21 (0.96-1.52); flavones, men: 0.86 (0.67-1.11), women: 0.90 (0.72-1.13); flavanones, men: 0.98 (0.75-1.28), women: 1.00 (0.80-1.26); flavan-3-ols, men: 1.00 (0.78-1.29), women: 0.96 (0.76-1.21); anthocyanins, men: 0.89 (0.69-1.15), women: 1.25 (0.98-1.60); polymers, men: 0.92 (0.71-1.18), women: 0.88 (0.69-1.11)). Conclusion: Our findings do not provide support for the hypothesis that a higher intake of flavonoids or any specific sub-class decrease risk of CRC. Citation Format: Katharina Nimptsch, Xuehong Zhang, Edward Giovannucci, Aedin Cassidy, Éilis J. O'Reilly, Tobias Pischon, Eric B. Rimm, Jennifer Lin, Walter C. Willett, Charles S. Fuchs, Kana Wu. Habitual intake of total flavonoids and flavonoid subclasses and risk of colorectal cancer in men and women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4820. doi:10.1158/1538-7445.AM2013-4820

Statins and colorectal cancer risk: a longitudinal study

Studies evaluating the association between statins and colorectal cancer (CRC) have used various methods to address bias and have reported mixed findings. We sought to assess the association in a large cohort of residents in Emilia-Romagna, Italy, using multiple methods to address different sources of confounding. We also sought to explore potential effect measure modification by sex. We conducted a retrospective cohort study using the 2003-2010 healthcare database of Emilia-Romagna, Italy. We identified all initiators of statins; initiators of glaucoma medications served as the comparison group to account for confounding by healthy user bias. We followed patients longitudinally to identify CRC cases in hospital discharge data. We used multivariable Cox regression analyses to adjust for confounding by CRC risk factors and we conducted a sensitivity analysis using propensity score matching. After multivariable adjustment, initiators of statins had a lower incidence rate of CRC as compared to initiators of glaucoma drugs [hazard ratio (HR) 0.79; 95 % CI 0.69-0.90]. In sex-stratified analyses we observed a protective effect in men (HR 0.77; 95 % CI 0.67-0.88) but not in women (HR 0.96; 95 % CI 0.82-1.1). Results were similar in propensity score analyses. After adjusting for observed risk factors, statin initiation versus glaucoma drug initiation was associated with a reduced risk of CRC in men but not in women. While this study is subject to many limitations, it corroborates a previous study that found sex differences in the association between statins and CRC.

Colonoscopy in Obese Patients: Time to Change Position

Improvements in the diagnostic and therapeutic potential of digestive endoscopy over the past few decades have notably increased the number of procedures performed, to the point that endoscopy is now almost considered to be routine. Changes in the epidemiology of colorectal cancer (CRC), which now represents the second leading cause of cancer-related death in America [1] and Europe [2], have also contributed to an increase in colonoscopies, since this procedure is considered the most accurate and effective method for early detection and prevention of CRC and premalignant precursor lesions. Colonoscopic removal of adenomatous polyps was proven to prevent approximately 80 % of CRCs [3, 4], and to lower the overall death rate from the disease [5]. In this context, several studies have reported that CRC screening is clinically useful [6] and cost-effective [7] in the average-risk population, significantly reducing mortality [8]. Obesity is a well-accepted risk factor for CRC [9, 10]; excessive body mass index (BMI) and physical inactivity are interrelated risk factors reported to account for between a fourth and a third of CRCs [11]. BMI is associated with an increased risk of incident CRC in men of all ages and in women between the ages 50–66 [12]. Indeed, excessive BMI is a modifiable risk factor associated with increased risk of adenoma and advanced adenoma recurrence [13]; unfortunately, weight loss has no effect on this risk of recurrence. In this context, and taking into account that obesity has reached epidemic proportions in America [14] and Europe [15], colonoscopy in obese patients represents a challenging issue for endoscopists, with much research focusing on the special features of colonoscopy in this population. For example, while a higher waist circumference has not been associated with a difficult cecal intubation [16–18], obesity constitutes an independent predictor of inadequate bowel preparation for colonoscopy [19], although these results were not reproduced when using a sodium picosulphatebased bowel preparation [20]. Furthermore, some endoscopic techniques and maneuvers normally required during the examination, including patient repositioning and the application of abdominal pressure, are more difficult to perform on obese patients. Extra difficulty is added when changing the position of a sedated obese patient. A recent study in which abdominal compression obtained with a fitted corset facilitates colonoscopy reported that extra abdominal compression and a change of position was used less frequently in the study subjects accompanied by less procedural pain [21]. In contrast, no definite data are available on the effect of a change from standard left lateral decubitus to prone position in facilitating colonoscopy in obese patients. This number of Digestive Diseases and Sciences includes a prospective randomized trial by Uddin and colleagues [22] which reports for the first time that starting sedated colonoscopy in prone position for male obese subjects (BMI [ 30 kg/ m) significantly shortens cecal intubation times with less need for patient repositioning. Additionally, the authors reported no differences in subjects’ perception of pain or their willingness to repeat the procedure when compared with obese subjects in whom the exploration was started using the standard left decubitus position. The subjects were sedated with benzodiazepines and narcotics under the endoscopist’s supervision due to safety concerns; patients scheduled for deep sedation with propofol or general anesthesia were excluded. Although 18 % of recruited patients had antecedents of sleep apnea, half of A. J. Lucendo (&) Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuellamos, s/n, 13700 Tomelloso, Ciudad Real, Spain e-mail: alucendo@vodafone.es

Sex Disparities in the Association of Lung Adenocarcinoma with Colorectal Cancer

Background: Most cancers share common risk factors. It might provide evidence of shared risk factors with cancers by investigating cross-country and cross-township comparisons.Methods: The data were obtained from International Association of Cancer Registries/World Health Organization and the National Cancer Registration Program of Taiwan. Age standardized incidence rates were calculated among gastric cancer, colorectal cancer and lung adenocarcinoma in 19 countries from 1995 to 1998. The Pearson correlations were also compared among 3 types of cancers for both sexes.Results: The incidence rates of gastric and colorectal cancer throughout different countries show male dominance with a male-to-female sex ratio of around 2 and 1.5, respectively. Significant cross-country correlations in colorectal cancer (r=0.918, p<0.001), gastric cancer (r=0.985, p<0.001) and lung adenocarcinoma (r=0.685, p=0.001) were observed between men and women. There was a significant international correlation between colorectal cancer and lung adenocarcinoma in men (r=0.526, p=0.021), but not in women. In cross-township comparisons of Taiwan, there were significant correlations in colorectal cancer (r=0.451, p<0.001), gastric cancer (r=0.486, p<0.001), and lung adenocarcinoma (r=0.217, p<0.001) between men and women. There were links of lung adenocarcinoma and gastric cancer (r=0.122, p=0.024) and colorectal cancer (r=0.128, p=0.018) in women, and lung adenocarcinoma and colorectal cancer in men (r=0.276, p<0.001).Conclusions: There were associations between lung adenocarcinoma and colorectal cancer between and in both sexes in Taiwan, but not in cross-country comparisons. The results suggest that some factor, like genes, may be important as determinants for the association between lung adenocarcinoma and colorectal cancer.

Influence of anthropometric factors on tumour biological characteristics of colorectal cancer in men and women: a cohort study

BackgroundObesity is a well established risk factor of colorectal cancer (CRC), but how body size influences risk of colorectal cancer defined by key molecular alterations remains unclear. In this study, we investigated the relationship between height, weight, body mass index (BMI), waist- and hip circumference, waist-hip ratio (WHR) and risk of CRC according to expression of beta-catenin, cyclin D1, p53 and microsatellite instability status of the tumours in men and women, respectively.MethodsImmunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status was assessed in tissue microarrays with tumours from 584 cases of incident CRC in the Malmö Diet and Cancer Study. Six anthropometric factors: height, weight, BMI, waist- and hip circumference, and WHR were categorized by quartiles of baseline measurements and relative risks of CRC according to expression of beta-catenin, cyclin D1, p53 and MSI status were calculated using multivariate Cox regression models.ResultsHigh height was associated with risk of cyclin D1 positive, and p53 negative CRC in women but not with any investigative molecular subsets of CRC in men. High weight was associated with beta-catenin positive, cyclin D1 positive, p53 negative and microsatellite stable (MSS) tumours in women, and with beta-catenin negative and p53 positive tumours in men. Increased hip circumference was associated with beta-catenin positive, p53 negative and MSS tumours in women and with beta-catenin negative, cyclin D1 positive, p53 positive and MSS tumours in men. In women, waist circumference and WHR were not associated with any molecular subsets of CRC. In men, both high WHR and high waist circumference were associated with beta-catenin positive, cyclin D1 positive and p53 positive tumours. WHR was also associated with p53 negative CRC, and waist circumference with MSS tumours. High BMI was associated with increased risk of beta-catenin positive and MSS CRC in women, and with beta-catenin positive, cyclin D1 positive and p53 positive tumours in men.ConclusionsFindings from this large prospective cohort study indicate sex-related differences in the relationship between obesity and CRC risk according to key molecular characteristics, and provide further support of an influence of lifestyle factors on different molecular pathways of colorectal carcinogenesis.

Association Between Sex Hormones and Colorectal Cancer Risk in Men and Women

There is observational and clinical evidence that indicates that sex hormones affect development of colorectal cancer in men and women. However, the relationship between endogenous sex hormone levels and colorectal cancer is unclear. We collected data on lifestyle, medical history, and diet (through 2008), along with blood samples, from the Nurses' Health Study, the Women's Health Study, the Health Professional Follow-up Study, and the Physicians' Health Study II. We measured plasma levels of estrone, estradiol, testosterone, sex hormone binding globulin (SHBG), and C-peptide among 730 women (293 cases of colorectal cancer and 437 healthy individuals as controls) and 1158 men (439 colorectal cancer cases and 719 controls) and used unconditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals. All statistical tests were 2-sided. Total testosterone, SHBG, and the ratio of estradiol to testosterone were associated with colorectal cancer in men after adjustments for matching and risk factors for colorectal cancer, including body mass index and plasma levels of C-peptide. The RRs in the highest relative to the lowest quartile were 0.62 for testosterone (95% confidence interval, 0.40-0.96), 0.65 for SHBG (95% confidence interval, 0.42-0.99), and 2.63 for the ratio (95% confidence interval, 1.58-4.36) (P values for trend ≤ .02). However, in women, only the ratio of estradiol to testosterone was (inversely) associated with colorectal cancer after adjustments for all factors (RR, 0.43; 95% confidence interval, 0.22-0.84; P value for trend = .03). On the basis of combined data from 4 population studies, there appears to be an association between levels of sex hormones and colorectal cancer risk in men. There also appears to be an inverse association between the ratio of estradiol to testosterone and colorectal cancer in postmenopausal women.