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.
What's new?
The relationship between calcium intake and colorectal cancer (CRC) risk is still unclear. In this study, the authors evaluated whether calcium intake affects CRC risk at various anatomic subsites, and over what length of time. They found that higher intake was associated with a significantly reduced risk of cancer of the colon, especially of the distal colon. Increased intake at least 10 years prior to diagnosis seemed to have the greatest impact. These results suggest that revised dietary guidelines for calcium intake may aid in the prevention of CRC.
Tea and coffee have antioxidant and neuroprotective effects. Observational studies suggest that tea and coffee intake may reduce cancer risk, but data on glioma risk are inconclusive. We evaluated ...the association between tea, coffee and caffeine intake and glioma risk in the female Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) and the male Health Professionals Follow‐Up Study (HPFS). Cumulative intake was derived from validated quadrennial food frequency questionnaires. Glioma cases were confirmed by medical record review. Multivariable‐adjusted hazard ratios of glioma by beverage intake category were estimated using Cox proportional hazards models. We documented 554 incident cases of glioma (256 in NHS, 87 in NHSII and 211 in HPFS). Compared to <1 cup/week, higher tea consumption was borderline inversely associated with glioma risk in pooled cohorts (hazard ratio HR = 0.73, 95% confidence interval CI: 0.49–1.10 for >2 cups/day, p‐trend = 0.05), but not in women (HR = 0.74, 95% CI: 0.47–1.18 for >2 cups/day, p‐trend = 0.11) or men (HR = 0.70, 95% CI: 0.30–1.60 for >2 cups/day, p‐trend = 0.30) separately. Overall, we observed no significant associations between caffeinated, decaffeinated or total coffee intake and glioma risk. There were no material differences in the results with baseline values, 8‐year lagged responses, or when limited to glioblastoma (n = 362). In three large prospective cohort studies, tea intake was borderline inversely associated with glioma risk. No significant associations were observed for coffee intake and glioma risk. These results merit further exploration in prospective studies.
What's new?
Few lifestyle factors have been associated with glioma risk. Nonetheless, intake of coffee and tea, owing to potential neuroprotective and antioxidant effects, are of particular interest as lifestyle factors that defend against glioma. Here, the authors analyzed data from food frequency questionnaires and medical records from three large prospective cohort studies in the United States to assess the relationship between tea and coffee intake and glioma risk. Analyses show that tea intake has a marginal inverse association with glioma risk. Meanwhile, caffeinated or decaffeinated coffee intake and total coffee consumption had no impact on risk.
Although adherence to healthy dietary guidelines has been associated with a reduced risk of several health outcomes, including cardiovascular diseases, type 2 diabetes, and some cancers, little is ...known about the role of dietary patterns in the development of hepatocellular carcinoma (HCC). We prospectively assessed the associations of three key commonly used a priori dietary patterns—the Alternative Healthy Eating Index‐2010 (AHEI‐2010), Alternate Mediterranean Diet (AMED), and Dietary Approaches to Stop Hypertension (DASH)—with risk of incident HCC in the Health Professionals Follow‐Up Study (HPFS) and the Nurses’ Health Study (NHS), two large prospective cohort studies. Diet was assessed almost every 4 years using validated food frequency questionnaires (FFQs). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. During up to 32 years of follow‐up, 160 incident HCC cases were identified. After adjustment for most HCC risk factors, participants in the highest tertile of Alternative Healthy Eating Index‐2010 (AHEI‐2010) had a multivariable HR of 0.61 (95% CI, 0.39‐0.95; Ptrend = 0.03), compared with those in the lowest tertile. There was a suggestive, but nonsignificant, inverse association for Alternate Mediterranean Diet (AMED; HR = 0.75; 95% CI, 0.49‐1.15; Ptrend = 0.18) and a null association for Dietary Approaches to Stop Hypertension (DASH; HR = 0.90; 95% CI, 0.59‐1.36; Ptrend = 0.61) in relation to the risk of HCC development. Conclusion: Our findings suggest that better adherence to the AHEI‐2010 may decrease the risk of developing HCC among U.S. adults. Future studies are needed to replicate our results, examine these associations in other populations, and elucidate the underlying mechanisms.
Background & Aims Limited data exist regarding the actual risk of developing advanced adenomas and cancer after polypectomy or the factors that determine risk. Methods We pooled individual data from ...8 prospective studies comprising 9167 men and women aged 22 to 80 with previously resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with the development of advanced colorectal neoplasms during surveillance. Results During a median follow-up period of 47.2 months, advanced colorectal neoplasia was diagnosed in 1082 (11.8%) of the patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%; standard error, 2.2) and those with an adenoma 20 mm in size or greater (19.3%; standard error, 1.5). Risk factor patterns were similar for advanced adenomas and invasive cancer. In multivariate analyses, older age ( P < .0001 for trend) and male sex (odds ratio OR, 1.40; 95% confidence interval CI, 1.19–1.65) were associated significantly with an increased risk for metachronous advanced neoplasia, as were the number and size of prior adenomas ( P < .0001 for trend), the presence of villous features (OR, 1.28; 95% CI, 1.07–1.52), and proximal location (OR, 1.68; 95% CI, 1.43–1.98). High-grade dysplasia was not associated independently with metachronous advanced neoplasia after adjustment for other adenoma characteristics. Conclusions Occurrence of advanced colorectal neoplasia is common after polypectomy. Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas.
Toxoplasma gondii (T gondii) is a common parasite that shows affinity to neural tissue and may lead to the formation of cysts in the brain. Previous epidemiologic studies have suggested an ...association between glioma and increased prevalence of T gondii infection, but prospective studies are lacking. Therefore, we examined the association between prediagnostic T gondii antibodies and risk of glioma in two prospective cohorts using a nested case‐control study design. Cases and matched controls were selected from the American Cancer Society's Cancer Prevention Study‐II Nutrition Cohort (CPSII‐NC) (n = 37 cases and 74 controls) and the Norwegian Cancer Registry's Janus Serum Bank (Janus) (n = 323 cases and 323 controls). Blood samples collected prior to diagnosis were analyzed for antibodies to two T gondii surface antigens (p22 and sag‐1), with individuals considered seropositive if antibodies to either antigen were detected. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for each cohort. In both cohorts, a suggestive increase in glioma risk was observed among those infected with T gondii (OR: 2.70; 95% CI: 0.96‐7.62 for CPSII‐NC; OR: 1.32, 95% CI: 0.85‐2.07 for Janus), particularly among participants with high antibody titers specific to the sag‐1 antigen (CPSII‐NC OR: 3.35, 95% CI: 0.99‐11.38; Janus OR: 1.79, 95% CI: 1.02‐3.14). Our findings provide the first prospective evidence of an association between T gondii infection and risk of glioma. Further studies with larger case numbers are needed to confirm a potential etiologic role for T gondii in glioma.
What's new?
The etiology of glioma remains poorly understood, with only a few known non‐modifiable risk factors identified. Previous ecological and case‐control studies have suggested an association between Toxoplasma gondii infection and increased glioma risk. Here, individuals who were seropositive for exposure to antigens from the tachyzoite stage of the parasite life cycle were more likely to be diagnosed with glioma in the 13 years following blood collection. The results provide the first prospective evidence of a potential association between T gondii infection and risk of glioma in adults and suggest that reducing exposure could provide an avenue to modify glioma risk.
Periodontal diseases including tooth loss might increase systemic inflammation, lead to immune dysregulation and alter gut microbiota, thereby possibly influencing colorectal carcinogenesis. Few ...epidemiological studies have examined the association between periodontal diseases and colorectal cancer (CRC) risk. We collected information on the periodontal disease (defined as history of periodontal bone loss) and number of natural teeth in the Nurses' Health Study. A total of 77,443 women were followed since 1992. We used Cox proportional hazard models to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjustment for smoking and other known risk factors for CRC. We documented 1,165 incident CRC through 2010. Compared to women with 25–32 teeth, the multivariable HR (95% CI) for CRC for women with <17 teeth was 1.20 (1.04–1.39). With regard to tumor site, the HRs (95% CIs) for the same comparison were 1.23 (1.01–1.51) for proximal colon cancer, 1.03 (0.76–1.38) for distal colon cancer and 1.48 (1.07–2.05) for rectal cancer. In addition, compared to those without periodontal disease, HRs for CRC were 0.91 (95% CI 0.74–1.12) for periodontal disease, and 1.22 (95% CI 0.91–1.63) when limited to moderate to severe periodontal disease. The results were not modified by smoking status, body mass index or alcohol consumption. Women with fewer teeth, possibly moderate or severe periodontal disease, might be at a modest increased risk of developing CRC, suggesting a potential role of oral health in colorectal carcinogenesis.
What's new?
Periodontal disease does not simply affect the mouth. It is also thought to increase systemic inflammation, trigger immune dysfunction, alter the microbiome and increase the risk of a number of cancers. Might it also increase colorectal cancer (CRC) risk? In this analysis of data from the Nurses' Health Study, the authors found that the risk of developing CRC increased by as much as 48% in women with periodontal disease. Cancer risk increased with the severity of tooth loss. These results suggest that oral health may affect factors involved in colorectal carcinogenesis.
Participant‐level meta‐analysis across multiple studies increases the sample size for pooled analyses, thereby improving precision in effect estimates and enabling subgroup analyses. For analyses ...involving biomarker measurements as an exposure of interest, investigators must first calibrate the data to address measurement variability arising from usage of different laboratories and/or assays. In practice, the calibration process involves reassaying a random subset of biospecimens from each study at a central laboratory and fitting models that relate the study‐specific “local” and central laboratory measurements. Previous work in this area treats the calibration process from the perspective of measurement error techniques and imputes the estimated central laboratory value among individuals with only a local laboratory measurement. In this work, we propose a repeated measures method to calibrate biomarker measurements pooled from multiple studies with study‐specific calibration subsets. We account for correlation between measurements made on the same person and between measurements made at the same laboratory. We demonstrate that the repeated measures approach provides valid inference, and compare it to existing calibration approaches grounded in measurement error techniques in an example describing the association between circulating vitamin D and stroke.
Two indexes exist to describe dietary inflammatory potential: an empirical dietary inflammatory pattern (EDIP) composed of food groups as reported on a food-frequency questionnaire (FFQ) and a ...literature-derived dietary inflammatory index (DII) composed mainly of nutrients.
We compared the ability of the 2 indexes to predict concentrations of inflammatory markers and hypothesized that the EDIP would be more predictive because it was derived on the basis of circulating inflammatory markers.
Both EDIP and DII scores were calculated from FFQ data reported by 5826 women in the Nurses' Health Study II and 5227 men in the Health Professionals Follow-Up Study. We used multivariable-adjusted linear regression analyses to calculate relative differences in concentrations of 4 plasma inflammatory markers—C-reactive protein (CRP; milligrams per liter), interleukin 6 (IL-6; picograms per milliliter), tumor necrosis factor α receptor 2 (TNFαR2; picograms per milliliter), and adiponectin (nanograms per milliliter)—in quintiles of the dietary indexes.
Spearman correlations between the EDIP and DII scores were modest (r = 0.29 and 0.21 for women and men, respectively; all P < 0.0001). Higher scores on both dietary indexes were associated with higher concentrations of inflammatory markers, although they were associated with lower adiponectin concentrations and there was no association between the DII and adiponectin in men. For example, percentage differences in concentrations of biomarkers in quintile 5 generally were higher (lower for adiponectin) than in quintile 1 (for the EDIP and DII, respectively—women: CRP, +60% and +49%; IL-6, +23% and +21%; TNFαR2, +7% and +4%; adiponectin, −21% and −14%; men: CRP, +38% and +29%; IL-6, +14% and +24%; TNFαR2, +9% and +5%; adiponectin, −16% and −4%.)
Despite design differences, the EDIP and DII both assess dietary inflammatory potential in men and women, with the EDIP showing a greater ability to predict concentrations of plasma inflammatory markers.
We examined the proportions of multiple types of breast cancers in the population that were attributable to established risk factors, focusing on behaviors that are modifiable at menopause. We ...estimated the full and partial population attributable risk percentages (PAR%) by combining the relative risks and the observed prevalence rates of the risk factors of interest. A total of 8,421 cases of invasive breast cancer developed in postmenopausal women (n = 121,700) in the Nurses' Health Study from 1980-2010. We included the following modifiable risk factors in our analyses: weight change since age 18 years, alcohol consumption, physical activity level, breastfeeding, and menopausal hormone therapy use. Additionally, the following nonmodifiable factors were included: age, age at menarche, height, a combination of parity and age at first birth, body mass index at age 18 years, family history of breast cancer, and prior benign breast disease. When we considered all risk factors (and controlled for age), the PAR% for invasive breast cancers was 70.0% (95% confidence interval: 55.0, 80.7). When considering only modifiable factors, we found that changing the risk factor profile to the lowest weight gain, no alcohol consumption, high physical activity level, breastfeeding, and no menopausal hormone therapy use was associated with a PAR% of 34.6% (95% confidence interval: 22.7, 45.4). The PAR% for modifiable factors was higher for estrogen receptor-positive breast cancers (PAR% = 39.7%) than for estrogen receptor-negative breast cancers (PAR% = 27.9%). Risk factors that are modifiable at menopause account for more than one-third of postmenopausal breast cancers; therefore, a substantial proportion of breast cancer in the United States is preventable.
Glioma is an aggressive neoplasm of the brain with poorly understood etiology. A limited number of pathogens have been examined as glioma risk factors, but data from prospective studies with ...infection status determined before disease are lacking. Herpesviruses comprise a large family of DNA viruses that infect humans and are linked to a range of chronic diseases. We conducted a prospective evaluation of the association between antibody to six human herpesviruses and glioma risk in the Janus Serum Bank (Janus) and the Cancer Prevention Study‐II (CPS‐II). In Janus and CPS‐II, the risk for glioma was not related to seroprevalence of herpes simplex virus‐1, varicella zoster virus, or human herpes viruses 6A or 6B. In Janus, seropositivity to either the Epstein Barr virus (EBV) EAD or VCAp18 antigen was associated with a lower risk of glioma (ORs: 0.55 95% CI 0.32‐0.94 and 0.57 95% CI 0.38‐0.85). This inverse association was consistent by histologic subtype and was observed for gliomas diagnosed up to two decades following antibody measurement. In Janus, seropositivity to at least one of three examined cytomegalovirus (CMV) antigens (pp150, pp52, pp28) was associated with an increased risk of nonglioblastoma (OR: 2.08 95% CI 1.07‐4.03). This association was limited to tumors diagnosed within 12 years of antibody measurement. In summary, we report evidence of an inverse association between exposure to EBV and glioma. We further report that CMV exposure may be related to a higher likelihood of the nonglioblastoma subtype.
What's new?
Although glioma is an aggressive cancer, little is known about environmental risk factors that influence its development and that could be leveraged for prevention or treatment. Such risk factors potentially include the herpesviruses cytomegalovirus (CMV) and Epstein‐Barr virus (EBV). Here, associations between antibodies against herpesviruses and glioma were investigated in two cohorts, including the Janus Serum Bank. In the Janus cohort, seropositivity to the EBV early antigen and viral capsid antigen were associated with reduced glioma risk, while seropositivity to CMV was associated with increased risk of the nonglioblastoma subtype. The findings offer insight into new opportunities for glioma prevention and treatment.
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