Concordance with the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention and colorectal cancer risk in Morocco: A large,population-based case–control study

The present study aimed to investigate associations between adherence to the recommendations on cancer prevention from the WCRF/AICR and colorectal cancer (CRC) risk in Morocco. Incident CRC cases (n = 1,516) and controls (n = 1,516) matched on age, sex and center, were recruited between September 2009 and February 2017 at five major hospitals located in Morocco. In-person interviews were conducted to assess habitual diet using a validated Food Frequency Questionnaire, physical activity and anthropometric measurements. Adherence to the WCRF/AIRC Recommendations was ranged from 0 (no adherence) to 6 (maximal adherence) and incorporating six WCRF/AICR components (food groups, physical activity and BMI). Multivariable odd ratios (OR_A) and 95% confidence intervals (CI) were calculated using conditional multivariate logistic regression models, with low adherence as referent, adjusting for potential confounding factors. Compared to those with the lowest adherence score, individuals in the highest WCRF/AICR score category had a statistically significant reduced risk for colon cancer (OR_A = 0.63, 95% CI 0.53–0.76); rectal cancer (OR_A = 0.52, 95% CI 0.43–0.63) and CRC overall (OR_A = 0.58, 95% CI 0.51–0.66). For individual score components, when comparing the lowest with the highest adherence category, CRC risk was significantly lower in the highest adherence category for body fatness (OR_A = 0.73; 95% CI 0.62–0.85), physical activity (OR_A = 0.70; 95% CI 0.60–0.82), plant foods (OR_A = 0.50; 95% CI 0.39–0.63) and red/processed meat (OR_A = 0.81; 95% CI 0.71–0.92). Our analysis indicated that greater adherence to the WCRF/AICR recommendations for cancer prevention may lower CRC risk in Morocco.     

Circulating anti‐Müllerian hormone and breast cancer risk: A study in ten prospective cohorts

A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (p_trend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (p_interaction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: OR_Q4–Q1 = 1.96, 95% CI = 1.46–2.64, p_trend <0.0001; ER+/PR?: OR_Q4–Q1 = 0.82, 95% CI = 0.40–1.68, p_trend = 0.51; ER?/PR+: OR_Q4–Q1 = 3.23, 95% CI = 0.48–21.9, p_trend = 0.26; ER?/PR?: OR_Q4–Q1 = 1.15, 95% CI = 0.63–2.09, p_trend = 0.60. The association was observed for both pre‐ (OR_Q4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (OR_Q4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (p_interaction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.     

Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort

Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre‐specific validated dietary questionnaires and composition data from the Phenol‐Explorer database. During an average of 11 years of follow‐up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93–1.18; p‐trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.     

A prospective evaluation of plasma polyphenol levels and colon cancer risk

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre‐diagnostic plasma polyphenols and colon cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (q_values) was computed to control for multiple comparisons. All statistical tests were two‐sided. After false discovery rate correction and in continuous log₂‐transformed multivariable models, equol (odds ratio [OR] per log₂‐value, 0.86, 95% confidence interval [95% CI] = 0.79–0.93; q_value = 0.01) and homovanillic acid (OR per log₂‐value, 1.46, 95% CI = 1.16–1.84; q_value = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41–0.91, p_trend = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17–2.53, p_trend < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.     

Erythrocyte membrane fatty acids and breast cancer risk: a prospective analysis in the nurses' health study II

The roles of specific fatty acids in breast cancer etiology are unclear, particularly among premenopausal women. We examined 34 individual fatty acids, measured in blood erythrocytes collected between 1996 and 1999, and breast cancer risk in a nested case‐control study of primarily premenopausal women in the Nurses' Health Study II. Breast cancer cases diagnosed after blood collection and before June 2010 (n = 794) were matched to controls and conditional logistic regression was used to estimate OR's (95% CI's) for associations of fatty acids with breast cancer; unconditional logistic regression was used for stratified analyses. Fatty acids were not significantly associated with breast cancer risk overall; however, heterogeneity by body mass index (BMI) was observed. Among overweight/obese women (BMI ≥ 25), several odd‐chain saturated (SFA, e.g. 17:0, OR_Q4vsQ1(95% CI) =1.85 (1.18 – 2.88), p_trend=0.006 p_int<0.001), trans (TFA, e.g. 18:1, OR_Q4vsQ1(95% CI) =2.33 (1.45 – 3.77), p_trend<0.001, p_int=0.007) and dairy‐derived fatty acids (SFA 15:0 + 17:0 + TFA 16:1n‐7t; OR_Q4vsQ1(95% CI) =1.83(1.16 – 2.89), p_trend=0.005, p_int<0.001) were positively associated, and n‐3 polyunsaturated fatty acids (n‐3 PUFA, e.g. alpha‐linolenic acid; OR_Q4vsQ1(95% CI) =0.57 (0.36 – 0.89), p_trend=0.017, p_int=0.03) were inversely associated with breast cancer. Total SFA were inversely associated with breast cancer among women with BMI < 25 (OR_Q4vsQ1(95% CI) =0.68 (0.46 – 0.98), p_trend=0.05, p_int=0.01). Thus, while specific fatty acids were not associated with breast cancer overall, our findings suggest positive associations of several SFA, TFA and dairy‐derived fatty acids and inverse associations of n‐3 PUFA with breast cancer among overweight/obese women. Given these fatty acids are influenced by diet, and therefore are potentially modifiable, further investigation of these associations among overweight/obese women is warranted.     

Dietary intake of fiber,whole grains and risk of colorectal cancer: An updated analysis according to food sources,tumor location and molecular subtypes in two large US cohorts

Epidemiologic evidence relating fiber intake to colorectal cancer (CRC) remains inconclusive and data are limited on different food sources of fiber and heterogeneity by tumor subsite and molecular profile. We prospectively followed for CRC incidence 90,869 women from the Nurses’ Health Study (1980–2012) and 47,924 men from the Health Professionals Follow-up Study (1986–2012), who completed a validated food frequency questionnaire every 4 years. Cox proportional hazards regression was used to examine the associations with CRC risk for total, cereal, fruit and vegetable fiber and whole grains. We also assessed the associations according to tumor subsites (proximal colon, distal colon and rectum) and molecular markers (microsatellite instability, BRAF mutation, CpG island methylator phenotype and KRAS mutation). We documented 3,178 CRC cases during 3,685,903 person-years of follow-up in the NHS and HPFS. Intake of total dietary fiber was not associated with CRC risk after multivariable adjustment in either women (hazard ratio [HR] comparing extreme deciles, 1.17; 95% CI, 0.92–1.48, p_trend = 0.55) or men (HR, 0.90; 95% CI, 0.67–1.21, p_trend = 0.47). Higher intake of cereal fiber and whole grains was associated with lower CRC risk in men with an HR of 0.75 (95% CI, 0.57–1.00) and 0.72 (95% CI, 0.54–0.96), respectively. No heterogeneity was detected by tumor subsite or molecular markers (p_{heterogeneity} > 0.05). Higher intake of total dietary fiber within the range of a typical American diet is unlikely to substantially reduce CRC risk. The potential benefit of cereal fiber and whole grains in men warrants further confirmation.     

Calcium intake and colorectal cancer risk: Results from the nurses' health study and health professionals follow‐up study

The relationship between calcium intake and colorectal cancer (CRC) risk remains inconclusive. We conducted this study to evaluate whether the association between calcium intake and CRC risk differs by anatomic subsite and determine the dose–response relationship for this association, as well as assess when in carcinogenesis calcium may play a role. We assessed calcium intake every 4 years and followed 88,509 women (1980–2012) in the Nurses' Health Study and 47,740 men (1986–2012) in the Health Professionals Follow‐Up Study. We documented 3,078 incident CRC cases. Total calcium intake (≥1,400 vs. <600 mg/d) was associated with a statistically significant lower risk of colon cancer (multivariable relative risk: 0.78, 95%CI: 0.65–0.95). Similar results were observed by different sources of calcium (from all foods or dairy products only). The inverse association was linear and suggestively stronger for distal colon cancer (0.65, 0.43–0.99) than for proximal colon cancer (0.94, 0.72–1.22, p‐_{common effects} = 0.14). Additionally, when comparing different latencies, the overall pattern suggested that the inverse association appeared to be stronger with increasing latency and was strongest for intakes 12–16 years before diagnosis. Comparing total calcium intakes of ≥1,400 vs. <600 mg/d for intake 12–16 y before diagnosis, the pooled RR (95% CIs) of CRC was 0.76 (0.64–0.91). Higher calcium intake was associated with a lower risk of developing colon cancer, especially for distal colon cancer. Overall inverse association was linear and did not differ by intake source. Additionally, calcium intake approximately 10 years before diagnosis appeared to be associated with a lower risk of CRC.     

Coffee consumption and the risk of colorectal cancer by anatomical subsite in Japan: Results from the HERPACC studies

Consumption of coffee, a popular beverage worldwide, has been associated with lower colorectal cancer (CRC) risk. Although CRC exhibits different biological characteristics by anatomical subsite, the possibly heterogeneous impact of coffee on CRC by anatomical subsite has remained unclear. Here, we conducted two case‐control studies to examine the association between coffee consumption and CRC risk as well as risk by anatomic subsite among Japanese using data from the Hospital‐based Epidemiological Research Program at Aichi Cancer Center I and II (HERPACC‐I and II). Subjects were enrolled in HERPACC‐I between 1988 and 2000 and in HERPACC‐II between 2001 and 2005. Coffee consumption was measured with a self‐administered questionnaire. A conditional logistic regression model was used to calculate odds ratios (ORs) of CRC with coffee consumption, adjusted for potential confounders of age, smoking, alcohol drinking, red meat intake, BMI, exercise, family history of CRC, and diabetes mellitus history. We estimated summary ORs by pooling study‐specific ORs with a fixed effects model. In total, 2,696 CRC cases and 13,480 non‐cancer outpatients as controls were included. Overall, compared to non‐drinkers, ORs of less than 1 cup/day, 1–2 cups/day and 3 or more cups/day for CRC were 0.88 (95% CI: 0.77–1.00), 0.90 (95% CI: 0.80–1.01) and 0.78 (95% CI: 0.65–0.92), respectively (trend‐p = 0.009). Subsite‐specific analysis revealed a significant inverse linear trend between coffee consumption and distal colon cancer (p‐trend = 0.048), and a tendency toward a lower risk of rectal cancer (p‐trend = 0.068). These findings suggest that coffee consumption might impact the prevention of CRC, especially distal colon cancer.     

The association between −1304T>G polymorphism in the promoter of MKK4 gene and the risk of sporadic colorectal cancer in southern Chinese population

MKK4 (mitogen‐activated protein kinase kinase 4, NM_003010.2), which belongs to the mitogen‐activated protein kinase pathways, possesses functions in tumorigenesis. We hypothesized the genetic variants in MKK4 gene may alter its functions and thus cancer risk. In current hospital‐based case‐control study of 706 patients with sporadic colorectal cancer (CRC) and 723 sex‐age–frequency‐matched control subjects in a southern Chinese population, we genotyped two polymorphisms of MKK4 promoter (i.e., ?1304T>G, rs3826392 and ?1044A>T, rs3809728) and assessed their associations with the risk of sporadic CRC. Compared with ?1304TT genotypes, ?1304TG had a significantly decreased risk of CRC (adjusted odds ratios [OR] = 0.56; 95% CI = 0.44–0.72; p = 3.53 × 10^?6), the ?1304GG carriers had a further decreased risk of CRC (OR = 0.40; 95% CI = 0.23–0.70; p = 1.32 × 10^?3), and there was a significant trend for an allele dose effect on risk of CRC (p_trend = 2.64 × 10^?7). The decreased risk associated with ?1304G variant genotypes (i.e., TG+GG) was more pronounced in the subjects older than 60 years (adjusted OR = 0.41; 95% CI = 0.29–0.57; p = 2.25 × 10^?7), in ever drinkers (adjusted OR = 0.41; 95% CI = 0.28–0.59; p = 2.42 × 10^?6). The age and alcohol drinking status interacted with ?1304G variant genotypes on reducing cancer risk (p values for interaction were 0.015 and 0.043, respectively). Western blotting analysis showed that the levels of Mkk4 protein in sporadic CRC neoplastic tissues were significantly higher in the carriers of ?1304G variant genotypes than that in those with ?1304TT genotypes. However, no significant association was observed between ?1044A>T polymorphism and risk of CRC. To the best of our knowledge, this is the first study of genetic variants in MKK4 and cancer susceptibility. Larger studies are needed to validate our findings. © 2009 UICC     

Mediation of associations between adiposity and colorectal cancer risk by inflammatory and metabolic biomarkers

Inflammation and hyperinsulinemia may drive associations between adiposity and colorectal cancer (CRC) risk, but few studies have examined this hypothesis using mediation analysis. We used inverse odds ratio weighting and logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for estimated total effects (OR^TE) of body mass index, waist circumference, and adult weight gain on CRC risk, and estimated effects operating through seven inflammatory and metabolic biomarkers (natural indirect effect; OR^NIE) or through paths independent of these biomarkers (natural direct effect; OR^NDE) among 209 CRC cases and 382 matched controls nested within the Health Professionals Follow-up Study, a prospective cohort of male health professionals. A one-interquartile range (IQR) increase in body mass index (3.6 kg/m²) was associated with an OR^TE of 1.40 (95% CI: 1.13, 1.73), which decomposed into an OR^NIE of 1.26 (95% CI: 0.97, 1.52) and an OR^NDE of 1.11 (0.87, 1.42), with possibly stronger mediation by these biomarkers for adult weight gain (IQR = 10.4 kg; OR^TE = 1.32 [95% CI: 1.06, 1.64]; OR^NIE = 1.47 [95% CI: 1.01, 1.81]; OR^NDE = 0.89 [95% CI: 0.72, 1.11]), but no mediation for waist circumference. Mediation appeared to be stronger for the metabolic biomarkers than the inflammatory biomarkers. Inflammatory and metabolic mechanisms may mediate associations between both body mass index and adult weight gain with CRC risk.     

Red and processed meat intake and cancer risk: Results from the prospective NutriNet‐Santé cohort study

The International Agency for Research on Cancer (WHO‐IARC) classified red meat and processed meat as probably carcinogenic and carcinogenic for humans, respectively. These conclusions were mainly based on studies concerning colorectal cancer, but scientific evidence is still limited for other cancer locations. In this study, we investigated the prospective associations between red and processed meat intakes and overall, breast, and prostate cancer risk. This prospective study included 61,476 men and women of the French NutriNet‐Santé cohort (2009–2015) aged ≥35 y and who completed at least three 24 hrs dietary records during the first year of follow‐up. The risk of developing cancer was compared across sex‐specific quintiles of red and processed meat intakes by multivariable Cox models. 1,609 first primary incident cancer cases were diagnosed during follow‐up, among which 544 breast cancers and 222 prostate cancers. Red meat intake was associated with increased risk of overall cancers [HR_Q5vs.Q1=1.31 (1.10–1.55), p_trend = 0.01) and breast cancer (HR_Q5vs.Q1 = 1.83 (1.33–2.51), p_trend = 0.002]. The latter association was observed in both premenopausal [HR_Q5vs.Q1=2.04 (1.03–4.06)] and postmenopausal women [HR_Q5vs.Q1=1.79 (1.26‐2.55)]. No association was observed between red meat intake and prostate cancer risk. Processed meat intake was relatively low in this study (cut‐offs for the 5th quintile = 46 g/d in men and 29 g/d in women) and was not associated with overall, breast or prostate cancer risk. This large cohort study suggested that red meat may be involved carcinogenesis at several cancer locations (other than colon‐rectum), in particular breast cancer. These results are consistent with mechanistic evidence from experimental studies.     

A prospective study of one‐carbon metabolism biomarkers and cancer of the head and neck and esophagus

Experimental and epidemiological data suggest that factors of one‐carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre‐diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post‐diagnosis all‐cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [OR_{Q4vs. Q1}] being 2.13 (95% confidence interval [95% CI] 1.13–4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (OR_{Q4vs. Q1} 0.63, 95% CI 0.35–1.16, p for trend 0.02). Subgroup analyses by anatomical sub‐site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8 × 10^?4), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck.     

Red and processed meat,nitrite, and heme iron intakes and postmenopausal breast cancer risk in the NIH‐AARP Diet and Health Study

Previous studies have shown inconsistent associations between red and processed meat intake and breast cancer risk. N‐nitroso compounds and heme iron have been hypothesized as contributing factors. We followed 193,742 postmenopausal women in the NIH‐AARP Diet and Health Study and identified 9,305 incident breast cancers (1995–2006). Dietary intake was assessed using a food frequency questionnaire at baseline. We adjusted daily intakes of meat, nitrite and heme iron for energy intake using the nutrient density method. We estimated multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) by quintiles of dietary exposures for all breast cancer, by stage (in‐situ, localized, regional/distant) and by estrogen/progesterone receptor (ER/PR) status using Cox proportional hazards regression. Total red meat intake was positively associated with risk of regional/distant cancer (p‐trend = 0.02). The risk was 25% higher in the highest vs. lowest intake quintile (95% CI = 1.03–1.52). Higher processed red meat intake (Q5 vs. Q1) was associated with 27% higher risk of localized breast cancer (95% CI = 1.01–1.27, p‐trend = 0.03) and a 19% higher risk of regional/distant cancer (95% CI = 0.98–1.44, p‐trend = 0.10). In addition, higher nitrite intake from processed red meat was positively associated with localized cancer (HR for Q5 vs. Q1 = 1.23, 95% CI = 1.09–1.39, p‐trend < 0.0001). Heme iron intake was positively associated with breast cancer risk overall and all cancer stages (p‐trend = 0.02–0.05). No heterogeneity was observed in risk associations by hormone receptor status. Our findings suggest that high consumption of red meat and processed meat may increase risk of postmenopausal breast cancer. Added nitrite and heme iron may partly contribute to these observed associations.     

Long-term status of predicted body fat percentage,body mass index and other anthropometric factors with risk of colorectal carcinoma: Two large prospective cohort studies in the US

Anthropometric measurements, such as body mass index (BMI), waist circumference, and body fat percentage, have been used as indicators of obesity. Despite evidence that excess body fat is a risk factor for colorectal carcinoma (CRC), the magnitude of the association of BMI and other obesity indicators with the long-term risk of CRC remains unclear. Utilizing a Cox proportional hazards regression model, we examined differential associations between predicted body fat percentage and BMI with the risk of CRC (n = 2,017). The associations between CRC incidence and different adiposity measurements were also assessed. Predicted body fat percentage had a similar increased risk of CRC risk as BMI. In multivariable-adjusted analyses, the hazard ratio for CRC in the second to fifth quintiles (compared to the first quintile) of predicted body fat percentage were 1.32, 1.31, 1.53 and 2.09 for men (p_trend < 0.001) and 0.91, 0.90, 0.98 and 1.15 for women (p_trend = 0.03). Among various anthropometric measurements, predicted fat mass and waist circumference were slightly more strongly associated with CRC risk than BMI. In conclusion, the novel anthropometric prediction equations provided further evidence that a greater amount of body fat might contribute to CRC risk in both sexes. An innovative approach enabled us to estimate the susceptibilities of specific body composition with CRC risk, in an inexpensive and minimally invasive manner. Furthermore, the typically used measures of BMI and waist circumference are robust measures of adiposity to predict cancer risk in a relatively healthy population.     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

Common genetic variants and risk for non‐Hodgkin lymphoma and adult T‐cell lymphoma/leukemia in Jamaica

We evaluated whether risk of non‐Hodgkin lymphoma (NHL), particularly adult T‐cell leukemia/lymphoma (ATL) related to human T‐lymphotropic virus (HTLV) infection was associated with 63 single nucleotide polymorphisms (SNPs) from 38 candidate genes. The 395 NHL cases registered in Jamaica were matched by age, sex, calendar‐year and HTLV serostatus to 309 controls from the same population. Interleukin 13 (IL13) Ex4+98A>G SNP (rs20541) was associated with decreased NHL risk (OR_AG/AA = 0.62,95% CI = 0.44–0.87, p = 0.006), as was vascular cell adhesion molecule‐1, VCAM1 Ex9+149G>A SNP (rs1041163) (OR_CT = 0.77, 95% CI = 0.54–1.10, OR_CC=0.35, 95% CI = 0.16–0.76, p‐trend = 0.007). Both results were stronger in analyses restricted to ATL cases and HTLV‐positive controls, suggesting a role for these genes in ATL etiology (IL13 OR_AG/AA = 0.54, 95% CI = 0.36–0.84, p = 0.005; VCAM1 OR_CT = 0.65, 95% CI = 0.42–1.01, OR_CC = 0.20, 95% CI = 0.08–0.54, p‐trend = 0.001). Confirmation of these results in Caribbean and other populations is needed. © 2009 UICC     

Prediagnostic circulating markers of inflammation and risk of prostate cancer

Accruing evidence suggests that inflammation plays a role in prostate carcinogenesis. However, studies evaluating this association using C‐reactive protein (CRP) and interleukin‐6 as markers of inflammation have reported conflicting results. We investigated the associations of three common markers of inflammation (CRP, fibrinogen and leukocyte count) with the risk of prostate cancer in a prospective cohort of 2,571 men from Finland. During an average follow‐up period of 24 years (21–26 years), 203 men from the cohort who developed prostate cancer were identified via linkage to the nationwide Finnish Cancer Registry. We investigated the associations between the markers and the risk of prostate cancer using Cox proportional hazards model, adjusting for potential confounders. Elevated prediagnostic leukocyte count was associated with an increased risk of prostate cancer. In multivariable adjusted model, the relative risk of prostate cancer among men in the highest tertile of leukocyte count compared to men in the lowest tertile was 1.60 (95% confidence interval [CI] = 1.10–2.29, p‐trend = 0.01). Circulating CRP and fibrinogen were not associated with increased risk. The corresponding relative risks for elevated CRP and fibrinogen concentrations were 1.08 (95% CI: 0.74–1.60, p‐trend = 0.56) and 1.25 (95% CI: 0.87–1.81, p‐trend = 0.14), respectively. Men with elevated leukocyte counts had a 2.57‐fold (95% CI: 0.99–6.79) increased risk of prostate cancer mortality. The increased risk associated with elevated leukocyte counts warrants confirmation in other studies. Larger studies should consider combining at least two markers or using an inflammation score derived from many inflammatory markers to evaluate prostate cancer risk.     

Consumption of meat,traditional and modern processed meat and colorectal cancer risk among the Moroccan population: A large-scale case–control study

The current study aimed to investigate the relationship between red and white meat subtypes, processed meat (divided into traditional “Khlii, Kaddid” and industrially processed meat) and colorectal cancer (CRC) risk, considering CRC subsites, in Moroccan adults. A case–control study was conducted including 2,906 matched case–control pairs recruited from the five largest university hospitals in Morocco. Dietary data were collected through a validated Food Frequency Questionnaire (FFQ). Multivariable odds ratios (OR) and 95% confidence intervals (CI), for the association of CRC risk with meat consumption (high vs. low intake), were estimated using conditional logistic regression models, adjusted for relevant confounding variables. Overall, consumption of red meat was positively associated with colon cancer and CRC risk (OR = 1.23, 95% CI = 1.05–1.44; OR = 1.14, 95% CI = 1.02–1.27), respectively. In contrast, no significant association was observed between the consumption of red meat and rectal cancer risk (OR = 1.05, 95% = 0.90–1.23). Interestingly, while processed meat from industrial processes was positively associated with colon cancer, rectal cancer and CRC (OR = 1.61, 95% CI = 1.27–2.04; OR = 1.73, 95% CI = 1.34–2.23; OR = 1.67, 95% CI = 1.41–1.98), processed meat prepared using traditional methods was inversely associated with colon cancer and CRC risk (OR = 0.74, 95% CI = 0.57–0.98; OR = 0.77, 95% CI = 0.64–0.93), respectively. Furthermore, positive associations were observed between poultry intake and colon cancer risk among men (OR = 1.27, 95% CI = 1.01–1.59). Our study showed similar associations between the consumption of red meat and CRC risk in Morocco as in developed countries, while inverse associations were found for traditionally processed meat products. This is the first study to investigate the differential effects of traditional vs. westernized processed meat products in a developing country. Other studies are needed to confirm these findings and to understand the physiological pathways underlying these associations.     

Glycemic load,glycemic index and breast cancer risk in a prospective cohort of Swedish women

High‐glycemic load diets have been hypothesized to increase the risk of breast cancer but epidemiologic studies have yielded inconsistent findings. We examined the associations of carbohydrate intake, glycemic index and glycemic load with risk of overall and hormone receptor‐defined breast cancer in the Swedish Mammography Cohort, a population‐based cohort of 61,433 women who completed a food frequency questionnaire at enrollment in 1987–1990. During a mean follow‐up of 17.4 years, we ascertained 2,952 incident cases of invasive breast cancer. Glycemic load but not carbohydrate intake or glycemic index was weakly positively associated with overall breast cancer risk (p for trend = 0.05). In analyses stratified by estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumors, we observed statistically significant positive associations of carbohydrate intake, glycemic index and glycemic load with risk of ER+/PR? breast cancer; the multivariate relative risks comparing extreme quintiles were 1.34 [95% confidence interval (CI) = 0.93–1.94; p for trend = 0.04] for carbohydrate intake, 1.44 (95% CI = 1.06–1.97; p for trend = 0.01) for glycemic index and 1.81 (95% CI = 1.29–2.53; p for trend = 0.0008) for glycemic load. No associations were observed for ER+/PR+ or ER?/PR? breast tumors. These findings suggest that a high carbohydrate intake and diets with high glycemic index and glycemic load may increase the risk of developing ER+/PR? breast cancer. © 2009 UICC     

Baseline serum C‐reactive protein and death from colorectal cancer in the NHANES III cohort

Several prospective studies suggest that C‐reactive protein (CRP), a nonspecific serologic marker of inflammation, might be linked to risk of colorectal cancer (CRC), whereas others have reported null or protective effects. We analyzed data from 7,072 participants (50–85 years) in the U.S. National Health and Nutrition Examination Survey III (1988–1994), a nationally representative cohort (n = 33,994; 2 months–85 years) with vital status follow‐up to 2000. Hazard ratios (HRs) for mortality associated with baseline clinically raised (≥1.00 mg/dL) and intermediate (≥0.22–0.99 mg/dL) CRP levels were estimated using Cox proportional hazards regression controlling for CRC risk factors. There were 59 deaths from CRC, 106 from other obesity‐related cancers (other‐ORCs) and 1,130 from cardiovascular disease (CVD). Participants with clinically raised CRP at baseline were found to have a statistically significant greater risk of CRC death (HRs = 2.36–2.47) in comparison to persons with undetected levels. HRs were lower for death from other‐ORC and CVD (1.82, 95% CI 1.05–3.15; 1.53, 95% CI 1.29–1.81, respectively). Intermediate CRP level was associated with a nonsignificant 10–21% increased risk for CRC death. HR for CRC death was higher among persons with a normal BMI (2.16, 95% 0.96–4.87, p = 0.06) compared to those who were overweight (1.22, 95% CI 0.53–2.78) or obese (1.23, 95% CI, 0.37–4.08). A similar pattern was observed for waist circumference. This effect modification suggests that the impact of chronic inflammation may be independent of excess body fat. Future research is recommended to confirm emerging data that elevated serologic CRP might reflect underlying colonic inflammation.