Changes in body composition during and after adjuvant or neo-adjuvant chemotherapy in women with breast cancer stage I-IIIB compared with changes over a similar timeframe in women without cancer.

PURPOSE: Body weight and body composition may change during and after adjuvant or neo-adjuvant chemotherapy for breast cancer. However, most studies did not include a comparison group of women without cancer, thus could not assess whether observed changes differed from age-related fluctuations in body weight and body composition over time. We assessed changes in body composition during and after chemotherapy in breast cancer patients compared with age-matched women not diagnosed with cancer. METHODS: We recruited 181 patients with stage I-IIIb breast cancer and 180 women without cancer. In patients, we assessed body composition using a dual-energy X-ray scan before start of chemotherapy (T1), shortly after chemotherapy (T2), and 6 months after chemotherapy (T3); for the comparison group, the corresponding time points were recruitment (T1) and 6 (T2) and 12 (T3) months. RESULTS: Fifteen percent of patients and 8% of the comparison group gained at least 5% in body weight between T1 and T3. Among the comparison group, no statistically significant changes in body weight, or body composition were observed over time. Body weight of patients significantly increased from baseline (72.1 kg ± 0.4 kg) to T2 (73.3 kg ± 0.4 kg), but decreased to 73.0 kg ± 0.4 kg after chemotherapy (T3). Lean mass of patients significantly increased from 43.1 kg ± 0.5 kg at baseline to 44.0 kg ± 0.5 kg at T2, but returned to 43.1 kg ± 0.5 kg at T3. There were no differential changes in fat mass over time between patients and the comparison group. CONCLUSIONS: Changes in body weight and body composition during and after chemotherapy for early stage breast cancer were modest, and did not differ substantially from changes in body weight and body composition among women without cancer.

A longitudinal mixed methods study on changes in body weight, body composition, and lifestyle in breast cancer patients during chemotherapy and in a comparison group of women without cancer: study protocol.

BACKGROUND: More than 60% of women diagnosed with early stage breast cancer receive (neo)adjuvant chemotherapy. Breast cancer patients receiving chemotherapy often experience symptoms such as nausea, vomiting and loss of appetite that potentially affect body weight and body composition. Changes in body weight and body composition may detrimentally affect their quality of life, and could potentially increase the risk of disease recurrence, cardiovascular disease and diabetes. To date, from existing single method (quantitative or qualitative) studies is not clear whether changes in body weight and body composition in breast cancer patients are treatment related because previous studies have not included a control group of women without breast cancer. METHODS: We therefore developed the COBRA-study (Change Of Body composition in BReast cancer: All-in Assessment-study) to assess changes in body weight, body composition and related lifestyle factors such as changes in physical activity, dietary intake and other behaviours. Important and unique features of the COBRA-study is that it used I) a "Mixed Methods Design", in order to quantitatively assess changes in body weight, body composition and lifestyle factors and, to qualitatively assess how perceptions of women may have influenced these measured changes pre-, during and post-chemotherapy, and II) a control group of non-cancer women for comparison. Descriptive statistics on individual quantitative data were combined with results from a thematic analysis on the interviews- and focus group data to understand patients' experiences before, during and after chemotherapy. DISCUSSION: The findings of our mixed methods study, on chemotherapy treated cancer patients and a comparison group, can enable healthcare researchers and professionals to develop tailored intervention schemes to help breast cancer patients prevent or handle the physical and mental changes they experience as a result of their chemotherapy. This will ultimately improve their quality of life and could potentially reduce their risk for other co-morbidity health issues such as cardiovascular disease and diabetes.

Perceptions of Dutch health care professionals on weight gain during chemotherapy in women with breast cancer.

PURPOSE: Dutch Health care professionals (HCPs) provide little information concerning health risks associated with weight gain during chemotherapy for breast cancer. Women with breast cancer have specified the need for more information on nutrition and physical activity to deal with weight gain. The aims of this study were to assess the perceptions of Dutch HCPs on weight gain during chemotherapy and in addition evaluate whether and what kind of information on dietary intake and physical activity HCPs provide to prevent/treat weight gain during (neo)adjuvant chemotherapy. METHODS: A qualitative study was conducted using semi-structured interviews with 34 HCPs involved in breast cancer care: general practitioners, oncologists, specialized nurses, and dieticians. RESULTS: To date, little information about nutrition, physical activity, and weight gain is given during chemotherapy because it is not part of most HCPs' training, it is not included in the guidelines and it is not the best time to bring up information in the opinion of HCPs. Weight gain was perceived as just a matter of a few kilos and not an important health issue during treatment. All HCPs felt it is better that women themselves addressed their weight gain after chemotherapy. CONCLUSION: More knowledge about health risks associated with chemotherapy-induced weight gain and how to combat these issues needs to be made readily available to the HCPs and should become part of their training. Existing patient guidelines should include information on how to prevent and/or reduce weight gain through self-management of nutrition intake and physical activity during and post chemotherapy.

Taste and smell perception and quality of life during and after systemic therapy for breast cancer.

PURPOSE: The purpose of the study was to assess self-reported taste and smell perception after chemotherapy in breast cancer patients compared with women without cancer, and to assess whether taste and smell perception is associated with quality of life after the end of chemotherapy. METHODS: We included 135 newly diagnosed breast cancer patients who completed chemotherapy and 114 women without cancer. Questionnaires on taste, smell, and quality of life were completed shortly after and 6 months after chemotherapy (patients) or at two moments with 6 months' time window in between (comparisons). RESULTS: Self-reported taste and smell perception were significantly lower in patients shortly after chemotherapy compared to the comparison group. Most patients recovered 6 months after chemotherapy, although patients who were still receiving trastuzumab then reported a lower taste and smell perception compared to patients who were not. A lower self-reported taste and smell were statistically significantly associated with a worse quality of life, social, emotional, and role functioning shortly after chemotherapy. Six months after chemotherapy, taste and smell were statistically significantly associated with quality of life, social and role functioning, but only in patients receiving trastuzumab. CONCLUSIONS: Most taste and smell alterations recovered within 6 months after the end of chemotherapy for breast cancer, but not for patients receiving trastuzumab. These results highlight the importance of monitoring taste and smell alterations during and after treatment with chemotherapy and trastuzumab, as they may impact quality of life.

Increasing awareness and knowledge of lifestyle recommendations for cancer prevention in Lynch syndrome carriers: Randomized controlled trial.

Lynch syndrome (LS) mutation carriers may reduce their cancer risk by adhering to lifestyle recommendations for cancer prevention. This study tested the effect of providing LS mutation carriers with World Cancer Research Fund-the Netherlands (WCRF-NL) health promotion materials on awareness and knowledge of and adherence to these recommendations. In this randomized controlled trial (n = 226), the intervention group (n = 114) received WCRF-NL health promotion materials. All LS mutation carriers were asked to fill out questionnaires at 2 weeks before (baseline, T0) and at 2 weeks (T1) and 6 months (T2) after the intervention. Linear mixed models were performed on awareness (0-7) and knowledge (0-7) of the recommendations, and on the secondary outcomes, that is adherence, distress, cancer worry, and risk perception. Compared with the control group, the intervention group became significantly more aware (overall mean difference = 1.24; 95%CI = 0.82-1.67) and obtained significantly improved knowledge of the recommendations (overall mean difference = 1.65; 95%CI = 1.27-2.03). Differences were significantly larger for T1 (Pinteraction = .003 and ≤.001, respectively) but remained significant for T2. No effect on secondary outcomes was found. In conclusion, provision of WCRF-NL health promotion materials increases awareness and knowledge of lifestyle recommendations for cancer prevention among LS mutation carriers without causing additional distress, but does not affect adherence.

Weight change during chemotherapy in breast cancer patients: a meta-analysis.

BACKGROUND: Weight gain during chemotherapy in women with breast cancer is commonly reported. However, there are important differences between studies that examined weight change during chemotherapy; e.g. type of chemotherapy, menopausal status, time between body weight measurements and sample size. The purpose of this meta-analysis was to quantify changes in body weight during chemotherapy for women with breast cancer, taking these differences into account. METHODS: We identified relevant studies using PubMed, Scopus and Embase databases. The search was limited to human studies published in English up to and including December 2015. Only studies among women with early stage breast cancer treated with chemotherapy, with reported body weight before and after chemotherapy and type of chemotherapy were included. Random-effect models were used, and heterogeneity between studies was explored through stratified analyses and meta-regression. Sensitivity analyses were done to explore whether a specific study markedly affected the results. RESULTS: In total 25 papers were found, including data from 2620 women. Overall, body weight increased during chemotherapy: 2.7 kg (95% CI 2.0, 7.5) with a high degree of heterogeneity (I2 = 94.2%). Stratified analyses showed weight gain in all strata, but did not substantially reduce heterogeneity. Univariate meta-regression showed less weight gain in prospective studies compared to chart review studies (-2.0, 95% CI: -3.1, -0.8). Studies including cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimes showed a greater weight gain compared to those that did not (2.2, 95% CI: 1.1, 3.3); and papers published until the year 2000 showed a greater weight gain compared to those published after 2000 (1.9, 95% CI:-0.8, 3.1). In the multivariate models only studies including CMF regimes and studies published until 2000 were associated with significant weight gain of respectively 1.3 and 1.4 kg. CONCLUSION: Despite the high heterogeneity, this meta-analysis shows significant weight gain during chemotherapy for women with breast cancer. Weight gain was more pronounced in papers published until 2000 and women receiving CMF as chemotherapy regime. Although weight gain after chemotherapy has decreased over the course of time, weight gain is still substantial and deserves clinical attention.

Differences in dietary intake during chemotherapy in breast cancer patients compared to women without cancer.

PURPOSE: Breast cancer patients receiving chemotherapy often experience symptoms such as nausea, vomiting and loss of appetite that potentially affect dietary habits. This study assessed the intake of energy, macronutrients and food groups before and during chemotherapy in breast cancer patients compared with women without cancer, and determined the association between symptoms and energy and macronutrient intake. METHODS: This study included 117 newly diagnosed breast cancer patients scheduled for chemotherapy and 88 women without cancer. Habitual intake before chemotherapy was assessed with a food frequency questionnaire. Two 24-h dietary recalls were completed on random days for each participant during the whole chemotherapy treatment for patients and within 6 months after recruitment for women without cancer. Shortly, after the dietary recall, participants filled out questionnaires on symptoms. RESULTS: Before chemotherapy, habitual energy and macronutrient intake was similar for breast cancer patients and women without cancer. During chemotherapy, breast cancer patients reported a significantly lower total energy, fat, protein and alcohol intake than women without cancer, as shown by a lower intake of pastry and biscuits, cheese, legumes and meat products. A decline in subjective taste perception, appetite and hunger and experiencing a dry mouth, difficulty chewing, lack of energy and nausea were associated with a lower energy intake. CONCLUSIONS: Symptoms induced by chemotherapy are associated with lower dietary intake and manifested by a lower intake of specific food groups. To ensure an optimal dietary intake during chemotherapy, it is important to monitor nutritional status and symptom burden during chemotherapy in breast cancer patients.

The proportion of postmenopausal breast cancer cases in the Netherlands attributable to lifestyle-related risk factors.

We aimed to estimate the proportion of Dutch postmenopausal breast cancer cases in 2010 that is attributable to lifestyle-related risk factors. We calculated population attributable fractions (PAFs) of potentially modifiable risk factors for postmenopausal breast cancer in Dutch women aged >50 in 2010. First, age-specific PAFs were calculated for each risk factor, based on their relative risks for postmenopausal breast cancer (from meta-analyses) and age-specific prevalence in the population (from national surveys) around the year 2000, assuming a latency period of 10 years. To obtain the overall PAF, age-specific PAFs were summed in a weighted manner, using the age-specific breast cancer incidence rates (2010) as weights. 95 % confidence intervals for PAF estimates were derived by Monte Carlo simulations. Of Dutch women >40 years, in 2000, 51 % were overweight/obese, 55 % physically inactive (<5 days/week 30 min activity), 75 % regularly consumed alcohol, 42 % ever smoked cigarettes and 79 % had a low-fibre intake (<3.4 g/1000 kJ/day). These factors combined had a PAF of 25.7 % (95 % CI 24.2-27.2), corresponding to 2,665 Dutch postmenopausal breast cancer cases in 2010. PAFs were 8.8 % (95 % CI 6.3-11.3) for overweight/obesity, 6.6 % (95 % CI 5.2-8.0) for alcohol consumption, 5.5 % (95 % CI 4.0-7.0) for physical inactivity, 4.6 % (95 % CI 3.3-6.0) for smoking and 3.2 % (95 % CI 1.6-4.8) for low-fibre intake. Our findings imply that modifiable risk factors are jointly responsible for approximately one out of four Dutch postmenopausal breast cancer cases. This suggests that incidence rates can be lowered substantially by living a more healthy lifestyle.

Determinants of adherence to recommendations on physical activity, red and processed meat intake, and body weight among lynch syndrome patients.

This study aimed to identify determinants of adherence to lifestyle and body weight recommendations for cancer prevention among Lynch Syndrome (LS) patients. Cross-sectional baseline data of LS patients participating in the Lifestyle & Lynch (LiLy) study was used to assess determinants of adherence to the World Cancer Research Fund cancer prevention recommendations on body weight, physical activity, and red and processed meat intake. Adherence and potential determinants of adherence were assessed using questionnaires. Multivariable logistic regression analyses were conducted to identify determinants of adherence. Of the 211 participants, 50.2% adhered to the body weight recommendation, 78.7% adhered to the physical activity recommendation, and 33.6% adhered to the red and processed meat recommendation. Being younger and having a higher level of education were associated with adherence to the recommendation on body weight. Having knowledge about the recommendation was associated with adherence to the recommendations on physical activity and red and processed meat. Results confirm that knowledge about recommendations for cancer prevention is an important determinant for adherence and suggest that strategies to increase knowledge should be included in lifestyle promotion targeted at LS patients, along with behavior change techniques influencing other modifiable determinants.

Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Previous studies of the association between intake of dairy products and colorectal cancer risk have indicated an inverse association with milk, however, the evidence for cheese or other dairy products is inconsistent. METHODS: We conducted a systematic review and meta-analysis to clarify the shape of the dose-response relationship between dairy products and colorectal cancer risk. We searched the PubMed database for prospective studies published up to May 2010. Summary relative risks (RRs) were estimated using a random effects model. RESULTS: Nineteen cohort studies were included. The summary RR was 0.83 (95% CI [confidence interval]: 0.78-0.88, I2=25%) per 400 g/day of total dairy products, 0.91 (95% CI: 0.85-0.94, I2=0%) per 200 g/day of milk intake and 0.96 (95% CI: 0.83-1.12, I2=28%) per 50 g/day of cheese. Inverse associations were observed in both men and women but were restricted to colon cancer. There was evidence of a nonlinear association between milk and total dairy products and colorectal cancer risk, P<0.001, and the inverse associations appeared to be the strongest at the higher range of intake. CONCLUSION: This meta-analysis shows that milk and total dairy products, but not cheese or other dairy products, are associated with a reduction in colorectal cancer risk.

Carbohydrates, glycemic index, glycemic load, and colorectal cancer risk: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Dietary carbohydrate, glycemic index, and glycemic load are thought to influence colorectal cancer risk through hyperinsulinemia. We review and quantitatively summarize in a meta-analysis the evidence from prospective cohort studies. METHODS: We searched the PubMed database for prospective studies of carbohydrate, glycemic index, and glycemic load and colorectal cancer risk, up to October 2011. Summary relative risks were estimated by the use of a random effects model. RESULTS: We identified 14 cohort studies that could be included in the meta-analysis of carbohydrate, glycemic index, and glycemic load and colorectal cancer risk. The summary RR for high versus low intake was 1.00 (95% CI: 0.87-1.14, I2 = 31%) for carbohydrate, 1.07 (95% CI: 0.99-1.16, I2 = 28%) for glycemic index, and 1.00 (95% CI: 0.91-1.10, I2 = 39%) for glycemic load. In the dose-response analysis, the summary RR was 0.95 (95% CI: 0.84-1.07, I2 = 58%) per 100 grams of carbohydrate per day, 1.07 (95% CI: 0.99-1.15, I2 = 39%) per 10 glycemic index units, and 1.01 (95% CI: 0.95-1.08, I2 = 47%) per 50 glycemic load units. Exclusion of one or two outlying studies reduced the heterogeneity, but the results were similar. CONCLUSION: This meta-analysis of cohort studies does not support an independent association between diets high in carbohydrate, glycemic index, or glycemic load and colorectal cancer risk.

Body composition and its association with fatigue in the first 2 years after colorectal cancer diagnosis.

PURPOSE: Persistent fatigue among colorectal cancer (CRC) patients might be associated with unfavorable body composition, but data are sparse and inconsistent. We studied how skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) at diagnosis are associated with fatigue up to 24 months post-diagnosis in stage I-III CRC patients. METHODS: SMI, SMR, VAT, and SAT were assessed among 646 CRC patients using pre-treatment computed tomography images. Fatigue at diagnosis, at 6, and 24 months post-diagnosis was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The association of SMI, SMR, VAT, and SAT with fatigue (yes/no) was assessed using confounder-adjusted restricted cubic spline analyses. RESULTS: Prevalence of fatigue at diagnosis was 18%, at 6 months 25%, and at 24 months 12%. At diagnosis, a significant (p = 0.01) non-linear association of higher levels of SAT with higher prevalence of fatigue was observed. Lower levels of SMR were linearly associated with higher prevalence of fatigue at 6 months post-diagnosis (overall association p = 0.02). None of the body composition parameters were significantly associated with fatigue at 24 months. CONCLUSION: Having more SAT was associated with more fatigue at diagnosis, while low levels of SMR were associated with more fatigue at 6 months post-diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Our results suggest that it may be interesting to investigate whether interventions that aim to increase SMR around the time of diagnosis may help to lower fatigue. However, more knowledge is needed to understand the mechanisms behind the association of SMR with fatigue.

Chemosensory perception and food preferences in colorectal cancer patients undergoing adjuvant chemotherapy.

BACKGROUND AND AIM: Cancer is one of the major public health problems, with colorectal cancer being one of the most occurring types of cancer. During treatment, patients may experience changes in their dietary intake due to side-effects of treatment, like changes in chemosensory perception, i.e. smell and taste function. This study investigated alterations in chemosensory perception and food preferences in colorectal cancer patients during and after adjuvant chemotherapy. METHODS: Objective olfactory and gustatory function were measured by the Sniffin' Sticks and the Taste Strips test. Subjective smell and taste perception were determined with a questionnaire, while food preferences were assessed with a computer-based ranking task. To investigate changes during chemotherapy, patients undergoing adjuvant chemotherapy were measured before the start, halfway through (approximately 3 months after the start of adjuvant chemotherapy), and within one month after finishing chemotherapy (longitudinal measurements, n = 15 patients). As a comparison group, colorectal cancer patients not undergoing chemotherapy (n = 20), underwent the same measurements at similar time points. To measure changes after treatment, chemosensory perception and food preferences of patients who had undergone chemotherapy treatment were measured once, either at 6, 12 or 24 months after diagnosis (cross-sectional measurements; n = 20 for all time points). Changes during treatment were assessed using linear mixed model analyses, and changes after treatment were assessed with a one-way ANOVA or a Kruskal Wallis test. RESULTS: Objective olfactory and gustatory function did not differ statistically significantly between any of the groups and at any time point during or after treatment (all p > 0.05). In contrast, subjective smell (F(1,84) = 8.17, p = 0.005) and taste (F(1,99) = 4.08, p = 0.046) perception were rated statistically significantly lower by patients undergoing chemotherapy than the comparison group during treatment. At 6 months after diagnosis, patients who underwent chemotherapy rated their subjective taste perception significantly lower than patients at 12 and 24 months after treatment (F(2,57) = 12.05, p = 0.002). Food preferences did not change during treatment, or thereafter (all p > 0.05). Preference for protein-rich foods was positively correlated with objective gustatory function (r = 0.36, p < 0.001), while the preference for low-energy foods showed a negative correlation with objective gustatory function (r = -0.28, p = 0.004). CONCLUSIONS: Similar to other cancer patient populations, mainly subjective smell and taste perception are affected in colorectal cancer patients undergoing adjuvant chemotherapy. Changes in objective olfactory and gustatory function in relation to chemotherapy were not detected by the tests used in our study nor did food preferences change. However, it should be noted that subjective changes in smell and taste perception can affect subsequent flavor perception and food enjoyment, which might negatively impact eating behavior and nutritional intake.

Low reported taste function is associated with low preference for high protein products in advanced oesophagogastric cancer patients undergoing palliative chemotherapy.

BACKGROUND & AIMS: Cancer patients undergoing palliative chemotherapy can experience a variety of chemosensory and food preference changes which may impact their nutritional status and quality of life. However, evidence of these changes in oesophagogastric cancer (OGC) patients is currently mostly qualitative and not supported by quantitative data. The aim of this study was to assess how self-reported and objective taste and smell function and food preferences change over time during chemotherapy in OGC patients. METHODS: This observational study included 15 advanced OGC patients planned for first line treatment with capecitabine and oxaliplatin. Participants completed two test sessions scheduled before start of cytotoxic treatment and after two cycles. Self-reported and objective taste and smell function and the macronutrient and taste preference ranking task were conducted at each test session. RESULTS: Self-reported taste and smell did not change upon chemotherapy. Objective taste function decreased during chemotherapy, although this was not statistically significant (p = 0.06), objective smell function did not change. Before and during chemotherapy, high protein foods were preferred over high carbohydrate and over low energy products, but food preferences did not change over time. A lower self-reported taste function correlated with a lower preference for high-protein products (ρ = 0.526, p = 0.003). CONCLUSION: This study suggests that objective taste function decreases during chemotherapy in OGC patients, but not smell function. A low reported taste function was related to a lower preference for high-protein products.

[Nutrition and oropharyngeal cancer]. / Voeding en kanker van de mond- en de keelholte.

The conclusion of a recent systematic review of the literature on the relation between nutrition, physical activity and cancer is that more than 30% of all cases of cancer can be prevented by improving nutrition and increasing physical activity. In The Netherlands, 1 out of 100 men and 1 out of 160 women develop oropharyngeal cancer. The major risk factors are smoking tobacco and excessive alcohol consumption. According to the systematic review of the literature, a substantial consumption of vegetables and fruit can reduce the risk of this type of cancer.

Low radiographic muscle density is associated with lower overall and disease-free survival in early-stage colorectal cancer patients.

BACKGROUND: In cancer patients with a poor prognosis, low skeletal muscle radiographic density is associated with higher mortality. Whether this association also holds for early-stage cancer is not very clear. We aimed to study the association between skeletal muscle density and overall mortality among early-stage (stage I-III) colorectal cancer (CRC) patients. Furthermore, we investigated the association between skeletal muscle density and both CRC-specific mortality and disease-free survival in a subset of the study population. METHODS: Skeletal muscle density was assessed in 1681 early-stage CRC patients, diagnosed between 2006 and 2015, using pre-operative computed tomography images. Adjusted Cox proportional hazard models were used to evaluate the association between muscle density and overall mortality, CRC-specific mortality and disease-free survival. RESULTS: The median follow-up time was 48 months (range 0-119 months). Low muscle density was detected in 39% of CRC patients. Low muscle density was significantly associated with higher mortality (low vs. normal: adjusted HR 1.91, 95% CI 1.53-2.38). After stratification for comorbidities, the association was highest in patients with ≥ 2 comorbidities (HR 2.11, 95% CI 1.55-2.87). Furthermore, low skeletal muscle density was significantly associated with poorer disease-free survival (HR 1.68, 95% CI 1.14-2.47), but not with CRC-specific mortality (HR 1.68, 95% CI 0.89-3.17) in a subset of the study population. CONCLUSION: In early-stage CRC patients, low muscle density was significantly associated with higher overall mortality, and worse disease-free survival.

[Folic acid fortification: prevention as well as promotion of cancer]. / Foliumzuurverrijking: zowel preventie als bevordering van kanker.

In many countries foods are fortified with folic acid to prevent neural-tube defects. Beneficial effects on cancer, cardiovascular diseases and dementia are also assumed. Fortification with folic acid is not allowed in The Netherlands, although exemption can be granted. As well as beneficial effects, harmful effects may also occur. In addition to masking vitamin-B12 deficiency, there is some evidence that folic acid may promote progression of established tumours in laboratory animals and humans. In addition, it has been hypothesized that fortification with folic acid may have further negative effects on cancer through genetic selection. Given the high prevalence of cancer, these potentially harmful effects should also be taken into account in the Dutch debate on the advantages and disadvantages of folic acid fortification.

Fermented dairy products, calcium, and colorectal cancer in The Netherlands Cohort Study.

Experimental studies suggest that an increased consumption of fermented dairy products and calcium might decrease the risk of colorectal cancer. The associations between fermented dairy products, dietary calcium, and colorectal cancer risk were investigated in a population with a wide variation in intake of dairy products. The Netherlands Cohort Study of diet and cancer started in 1986 when 120,852 Dutch men and women, ages 55-69, filled out a questionnaire concerning dietary patterns and lifestyle. The present analysis is based on 3.3 years of follow-up and includes 215 incident cases of colon cancer and 111 incident cases of rectal cancer, excluding cases diagnosed in the first year of follow-up. After adjustment for potential confounding variables, colorectal cancer risk was weakly inversely associated with the consumption of fermented milk [relative rate (RR) in the highest category of intake compared to nonusers, 0.89; 95% confidence interval (CI), 0.60, 1.33], unfermented milk (RR, 0.86; 95% CI, 0.57, 1.29), and cheese (RR, 0.88; 95% CI, 0.59, 1.33). However, category-specific relative rates and tests for trends were not statistically significant. For fermented milk, the inverse association was limited to colon cancer (RR, 0.70; 95% CI, 0.43, 1.15; trend, P = 0.33). In crude and multivariate models, total dietary calcium intake (highest versus lowest quintile, RR, 0.92; 95% CI, 0.64, 1.34) and calcium from fermented dairy products (RR, 1.14; 95% CI, 0.77, 1.68) were not significantly associated with colorectal cancer risk. Calcium from unfermented dairy products was inversely associated with rectal cancer risk (RR, 0.55; 95% CI, 0.30, 1.04; trend, P = 0.03). After 3.3 years of follow-up, these data are not consistent with a substantially decreased risk of colorectal cancer with increased intake of fermented dairy products and dietary calcium.

Lack of association between the C677T MTHFR polymorphism and colorectal hyperplastic polyps.

Colorectal hyperplastic polyps are benign lesions that share many risk factors with colorectal adenomas and cancers. Low folate intakes are associated with an increased risk of colon cancer. The enzyme 5,10-methylene-tetrahydrofolate reductase (MTHFR) may be linked to DNA methylation and nucleotide synthesis and thus play a role in the etiology of colorectal neoplasia. We investigated an association between the common MTHFR polymorphism (C677T) and colorectal hyperplastic polyps within the Minnesota Cancer Prevention Research Unit case-control study. Cases (n = 200) were diagnosed with colonoscopically confirmed hyperplastic polyps; controls (n = 645) were derived from the same gastroenterology practice and were polyp-free at colonoscopy. Dietary intakes were estimated from a self-administered food-frequency questionnaire prior to colonoscopy. Multivariate adjusted odds ratios (ORs) and 95% confidence intervals for MTHFR status were 0.8 (0.6-1.2; CT versus CC wild-type) and 0.9 (0.5-1.6; TT versus CC). In subgroup analyses stratified on dietary intakes of folate, vitamin B12, vitamin B6, or methionine, those with the TT genotype and either low intakes of folate or vitamin B6 were at increased risk relative to those with normal or high vitamin intake. However, most 95% confidence intervals included 1.0, and no consistent trends were observed. In contrast to our findings on colorectal adenomas, increasing alcohol consumption was associated with an elevated risk of colorectal hyperplastic polyps, regardless of genotype. The MTHFR (C677T) variant genotype does not appear to be related to risk of colorectal hyperplastic polyps, and there is no convincing evidence that MTHFR shows a different relation to risk, dependent on dietary intakes of nutrients related to its pathway.

Meat consumption, genetic susceptibility, and colon cancer risk: a United States multicenter case-control study.

Meat consumption may especially increase risk of colon cancer when the meat is prepared at high temperatures and consumed by subjects with an inherited susceptibility to well-done meat. In this United States case-control study, the association between meat consumption, genetic susceptibility, and colon cancer risk was studied. Meat consumption data were available from a detailed diet history questionnaire and from questions about methods of preparation. Molecular variants in the carcinogen-metabolizing genes NAT2 and GSTM1 were determined in DNA extracted from WBCs. A total of 1542 cases and 1860 population-based controls were included in these analyses. The amount of red and white meat consumed was not associated with overall colon cancer risk. Processed meat consumption was weakly positively associated with colon cancer risk in men only (odds ratio for highest versus lowest quintile of intake = 1.4, 95% confidence interval = 1.0-1.9). The frequency of fried, broiled, baked, or barbecued meat, use of drippings, and doneness of meat were not significantly associated with risk. The Mutagen Index, as an estimate for exposure to mutagenic or carcinogenic substances, was slightly positively associated with colon cancer risk in men (odds ratio = 1.3, 95% confidence interval = 1.0-1.7). No significant associations with colon cancer risk were observed for different NAT2 and GSTM1 gene variants. The observed associations with processed meat and the Mutagen Index were strongest for those with the intermediate or rapid NAT2 acetylator phenotype. Associations were not markedly influenced by lack of the GSTM1 gene. This study provides little support for an association between meat consumption and colon cancer risk but does provide some, albeit not strong, evidence for a modifying effect of molecular variants of the NAT2 gene.