Nut and peanut butter intake and the risk of colorectal cancer and its anatomical and molecular subtypes: the Netherlands Cohort Study.

Nut intake has been associated with reduced total cancer-related mortality, but evidence for colorectal cancer (CRC) risk is inconclusive. We investigated the associations between nut and peanut butter intake and anatomical CRC subtypes. To account for molecular heterogeneity, associations between nut and peanut butter intake and colorectal tumors harboring APC, KRAS or BRAF mutations, p53 overexpression or microsatellite instability were examined in secondary analyses. In the Netherlands Cohort Study (n = 120 852), lifestyle habits were measured with a questionnaire in 1986. After 20.3 years follow-up, 3567 CRC cases were included in case-cohort analyses. For the analyses of molecular CRC subtypes, 574 cases were included after 7.3 years follow-up. In categorical analyses, total nut intake was not significantly associated with CRC [HR (95% CI) 10+ g/day versus non-consumers = 0.94(0.78-1.15) in men; 0.96(0.75-1.22) in women]. In restricted cubic spline analyses, significant non-linear inverse associations with rectal cancer were observed for total nut, peanut and peanut butter intake in women, and borderline significant non-linear inverse associations for total nut and peanut intake in men. Regarding the molecular CRC subtypes, peanut butter intake was significantly associated with an increased risk of colorectal tumors that did not develop through the serrated neoplasia pathway in men [HR (95% CI) per 5 g/day increment = 1.22(1.07-1.38)]. Nut and peanut butter intake are non-linearly inversely associated with rectal cancer risk in women. In men, nut intake is borderline significantly non-linearly associated with a reduced rectal cancer risk. Peanut butter is associated with an increased risk of colorectal tumors that do not develop through the serrated neoplasia pathway in men.

Tree nut, peanut, and peanut butter intake and risk of postmenopausal breast cancer: The Netherlands Cohort Study.

PURPOSE: Nut intake has been associated with reduced mortality and risk of cardiovascular diseases, but there is only limited evidence on cancer. We investigated the relationship between nut intake and risk of postmenopausal breast cancer, and estrogen/progesterone receptor (ER/PR) subtypes. METHODS: In The Netherlands Cohort Study, 62,573 women aged 55-69 years provided information on dietary and lifestyle habits in 1986. After 20.3 years of follow-up, 2,321 incident breast cancer cases and 1,665 subcohort members were eligible for multivariate case-cohort analyses. RESULTS: Total nut intake was significantly inversely related to ER negative (ER -) breast cancer risk, with HR 0.55 (95% CI 0.33-0.93) for those consuming at least 10 g nuts/day versus non-consumers (p trend = 0.025). There were no significant inverse associations with ER + or total breast cancer. While there was no variation between PR subtypes, the ER-PR- subtype was also significantly inversely associated with nut intake, with HR 0.53 (95% CI 0.29-0.99), p trend = 0.037. Intake of peanuts and tree nuts separately was also inversely related to ER - breast cancer subtypes, while no associations were found with peanut butter intake. CONCLUSIONS: Our findings suggest an inverse association between nut intake and ER - breast cancer, and no association with total or hormone receptor-positive subtypes.

Tree nut, peanut, and peanut butter consumption and the risk of gastric and esophageal cancer subtypes: the Netherlands Cohort Study.

BACKGROUND: Nut consumption has been associated with reduced cancer-related mortality. However, it is unclear whether nut consumption also reduces the risk of esophageal and gastric cancer subtypes. We prospectively investigated the relationship of tree nut, peanut, and peanut butter intake with risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in the Netherlands Cohort Study. METHODS: In 1986, 120,852 males and females, aged 55-69 years, completed a baseline questionnaire on diet and cancer risk factors. After 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA cases, and 3,720 subcohort members were available for multivariable Cox regression analyses, using a case-cohort approach. RESULTS: Increased total nut consumption was significantly associated with a decreased risk of ESCC and GNCA [HRs (95% CIs) for 10 + g/day vs. nonconsumers = 0.54 (0.30-0.96) and 0.73 (0.55-0.97), respectively], but not with EAC and GCA risk. Similar trends were observed for tree nut and peanut intake, which were mostly nonsignificant. For peanut butter intake, no significant associations were found. When excluding the first four years of follow-up to reduce the possible influence of reversed causation, the relation between nut consumption and ESCC risk attenuated, but remained inverse. CONCLUSIONS: Our findings suggest that increased tree nut and peanut consumption is inversely associated with GNCA risk and possibly with ESCC risk, but not with the risk of the other esophageal and gastric cancer subtypes.

Nut and Peanut Butter Consumption and the Risk of Total Cancer: A Prospective Cohort Study.

BACKGROUND: Nut intake has been associated with reduced cancer-related mortality, but there is very limited evidence on total cancer risk. We investigated the associations of nut and peanut butter intake with the risk of total cancer and smoking- and alcohol-related cancer subgroups. METHODS: In the prospective Netherlands Cohort Study, 120,852 men and women aged 55 to 69 years provided information on lifestyle and dietary habits at baseline in 1986. After 20.3 years of follow-up, 19,255 total cancer cases and 3,499 subcohort members were included in multivariable-adjusted Cox regression analyses, using a case-cohort approach. RESULTS: No significant associations were found between total nut, tree nut, peanut, and peanut butter intake and total cancer risk in men and women. There were also no significant associations with smoking-(un)related and alcohol-(un)related cancers in both sexes. CONCLUSIONS: Our findings suggest that nut and peanut butter intake are not associated with a reduced risk of total cancer in men or women. IMPACT: Nut and peanut butter consumption are not related to the risk of total cancer.

Nut and peanut butter intake are not directly associated with the risk of endometrial or ovarian cancer: Results from a Dutch prospective cohort study.

BACKGROUND & AIMS: Nut intake has been associated with reduced cancer-related mortality and cancer risk. However, very few studies investigated the association between nut consumption and the risk of endometrial and ovarian cancer, with inconclusive results. We prospectively examined the relation between total nut, tree nut, peanut, and peanut butter intake and the risk of endometrial and ovarian cancer in the prospective Netherlands Cohort Study (NLCS). METHODS: In 1986, 62,573 women aged 55-69 years were included in the NLCS. At baseline, all participants filled in a questionnaire and a subcohort of 2589 women was randomly selected. After 20.3 years of follow-up, 389 endometrial and 347 ovarian cancer cases with complete data were included in the analysis. Hazard ratios (HRs) were calculated in multivariable-adjusted Cox regression analyses, using a case-cohort approach. RESULTS: Compared to nonconsumers, the HRs (95% confidence intervals) for women consuming 10 + g total nuts/day were 1.23 (0.82-1.87) for endometrial cancer and 0.84 (0.57-1.24) for ovarian cancer. For tree nut, peanut, and peanut butter intake, also no significant relations with endometrial or ovarian cancer were observed. In the endometrial cancer analyses, significant interactions of total nut intake with body mass index and cigarette smoking status were found. CONCLUSIONS: The results of this study suggest that intake of total nuts, tree nuts, peanuts, and peanut butter is not related to the risk of endometrial or ovarian cancer. The observed interactions in the endometrial cancer analyses, in particular with cigarette smoking status, require confirmation in other studies.

Nut and peanut butter consumption and the risk of lung cancer and its subtypes: A prospective cohort study.

OBJECTIVES: Nut consumption has been associated with reduced cancer-related mortality, but evidence for a relation between nut intake and lung cancer risk is limited. We investigated the association between total nut, tree nut, peanut, and peanut butter intake and the risk of lung cancer and its subtypes in the Netherlands Cohort Study. MATERIALS AND METHODS: In 1986, dietary and lifestyle habits of 120,852 participants, aged 55-69 years, were measured with a questionnaire. After 20.3 years of follow-up, 3720 subcohort members and 2861 lung cancer cases were included in multivariable case-cohort analyses. RESULTS: Total nut intake was not significantly associated with total lung cancer risk in men or women. For small cell carcinoma, a significant inverse association with total nut intake was observed in men after controlling for detailed smoking habits (HR (95%CI) for 10+ g/day vs. nonconsumers: 0.62 (0.43-0.89), p-trend: 0.024). Inverse relations with small cell carcinoma were also found for tree nut and peanut intake in men in continuous analyses (HR (95%CI) per 5 g/day increment: 0.70 (0.53-0.93) and 0.93 (0.88-0.98), respectively). For the other lung cancer subtypes, no significant associations were seen in men. Nut intake was not related to the risk of lung cancer subtypes in women, and no associations were found for peanut butter in both sexes. CONCLUSION: Increased nut intake might contribute to the prevention of small cell carcinoma in men. No significant associations were found in men for the other subtypes or total lung cancer, in women, or for peanut butter intake.

Total nut, tree nut, peanut, and peanut butter intake and the risk of prostate cancer in the Netherlands Cohort Study.

BACKGROUND: The consumption of nuts has been associated with a reduction of cancer risk, but only a few studies have examined the effects of nuts on prostate cancer risk. The current study prospectively investigated the association between the consumption of total nuts, tree nuts, peanuts, and peanut butter and the risk of total, advanced, and non-advanced prostate cancer. METHODS: The association between nuts and prostate cancer was evaluated in the Netherlands Cohort Study, which was conducted among 58,279 men aged 55-69 year at baseline. A case-cohort approach was used for data processing and analyses. After 20.3 years of follow-up, 3868 incident prostate cancer cases and 1979 subcohort members were available for multivariable Cox regression analyses. RESULTS: For total, advanced, and non-advanced prostate cancer, no significant associations were found for total nuts (total prostate cancer: hazard ratio (HR) (95%CI) for 10+ g/day vs. non-consumers = 1.09 (0.92-1.29), Ptrend = 0.409). No significant associations were observed for tree nuts and peanuts for total, advanced, and non-advanced prostate cancer risk. Peanut butter consumption was associated with a significantly increased risk of non-advanced prostate cancer (HR (95%CI) for 5+ g/day vs. non-consumers = 1.33 (1.08-1.63), Ptrend = 0.008), but not with total or advanced prostate cancer. CONCLUSIONS: No significant associations were found between total nut, tree nut, and peanut consumption and total, advanced, and non-advanced prostate cancer. Peanut butter might be associated with an increased non-advanced prostate cancer risk.

Total Nut, Tree Nut, Peanut, and Peanut Butter Consumption and the Risk of Pancreatic Cancer in the Netherlands Cohort Study.

Background: Nut intake has been associated with decreased cancer-related mortality, but few studies have examined the potential of nuts in the chemoprevention of pancreatic cancer. We prospectively investigated the association of total nut, tree nut, peanut, and peanut butter consumption with pancreatic cancer risk.Methods: In the Netherlands Cohort Study, 120,852 men and women completed a baseline questionnaire, including a food frequency questionnaire, in 1986. After 20.3 years of follow-up, 583 incident pancreatic cancer cases, including 349 microscopically confirmed pancreatic cancer (MCPC) cases, were included in multivariable case-cohort analyses.Results: Increased total nut consumption was associated with a nonsignificantly decreased MCPC risk in men [HR (95% confidence interval) for 10+ g/d vs. nonconsumers = 0.72 (0.47-1.11), Ptrend = 0.163]. No clear association was found in women. For tree nut and peanut consumption, nonsignificant inverse associations were observed in men. In women, no or unclear associations were found for tree nut and peanut consumption. Peanut butter intake was related to a significantly reduced risk of MCPC in men [HR (95% confidence interval) for 5+ g/d vs. nonconsumers = 0.53 (0.28-1.00), Ptrend = 0.047], but this relation was not clear in women. Evidence for a nonlinear dose-response relation with MCPC was found for tree nut intake only. The associations were weaker when looking at total pancreatic cancer.Conclusions: Our results suggest that nuts and peanut butter might reduce pancreatic cancer risk in men. In women, no or unclear associations were found.Impact: Nut consumption might reduce the risk of pancreatic cancer in men. Cancer Epidemiol Biomarkers Prev; 27(3); 274-84. ©2018 AACR.

Cost-effectiveness of longer-term versus shorter-term provision of antibiotics in patients with persistent symptoms attributed to Lyme disease.

BACKGROUND: The treatment of persistent symptoms attributed to Lyme disease remains controversial. Recently, the PLEASE study did not demonstrate any additional clinical benefit of longer-term versus shorter-term antibiotic treatment. However, the economic impact of the antibiotic strategies has not been investigated. METHODS: This prospective economic evaluation, adhering a societal perspective, was performed alongside the PLEASE study, a multicenter, placebo-controlled, double-blind 1:1:1 randomized clinical trial in which all patients received open-label intravenous ceftriaxone for two weeks before the 12-week randomized blinded oral antibiotic regimen (doxycycline, clarithromycin plus hydroxychloroquine, or placebo). Between 2010 and 2013, patients (n = 271) with borreliosis-attributed persistent symptoms were enrolled and followed for one year. Main outcomes were costs, quality-adjusted life years, and incremental net monetary benefit of longer-term versus shorter-term antibiotic therapy. RESULTS: Mean quality-adjusted life years (95% CI) were not significantly different (p = 0.96): 0.82 (0.77-0.88) for ceftriaxone/doxycycline (n = 82), 0.81 (0.76-0.88) for ceftriaxone/clarithromycin-hydroxychloroquine (n = 93), and 0.81 (0.76-0.86) for ceftriaxone/placebo (n = 96). Total societal costs per patient (95% CI) were not significantly different either (p = 0.35): €11,995 (€8,823-€15,670) for ceftriaxone/doxycycline, €12,202 (€9,572-€15,253) for ceftriaxone/clarithromycin-hydroxychloroquine, and €15,249 (€11,294-€19,781) for ceftriaxone/placebo. Incremental net monetary benefit (95% CI) for ceftriaxone/doxycycline compared to ceftriaxone/placebo varied from €3,317 (-€2,199-€8,998) to €4,285 (-€6,085-€14,524) over the willingness-to-pay range, and that of ceftriaxone/clarithromycin-hydroxychloroquine compared to ceftriaxone/placebo from €3,098 (-€888-€7,172) to €3,710 (-€4,254-€11,651). For every willingness-to-pay threshold, the incremental net monetary benefits did not significantly differ from zero. CONCLUSION: The longer-term treatments were similar with regard to costs, effectiveness and cost-effectiveness compared to shorter-term treatment in patients with borreliosis-attributed persistent symptoms after one year of follow-up. Given the results of this study, and taking into account the external costs associated with antibiotic resistance, the shorter-term treatment is the antibiotic regimen of first choice.