Circulating prediagnostic interleukin‐6 and C‐reactive protein and prostate cancer incidence and mortality

Interleukin‐6 (IL‐6) and C‐reactive protein (CRP) are elevated in prostate cancer patients, but the role of prediagnostic levels of these inflammatory mediators on prostate cancer outcomes is unclear. We undertook a large, prospective case‐control study to evaluate the relation between prediagnostic levels of IL‐6 and CRP and prostate cancer incidence and mortality. We also investigated the role of the IL‐6 (?174 G/C) polymorphism in relation to circulating levels of IL‐6 and CRP, as well as cancer risk and mortality. We used unconditional logistic regression that adjusted for matching factors to analyze prostate cancer risk. For analyses of prostate cancer mortality, we conducted survival analyses in cases. Because of the strong link between inflammatory markers and body mass index (BMI), we assessed interactions between BMI and plasma levels on prostate cancer outcomes. Neither IL‐6 nor CRP plasma levels varied significantly by IL‐6 genotype. Genotype was not associated with prostate cancer risk or survival. Though neither IL‐6 nor CRP was associated with prostate cancer incidence overall, we observed a statistically significant interaction between IL‐6 and BMI on prostate cancer incidence (p_interaction < 0.01). Increasing IL‐6 levels were positively associated with risk in healthy weight men, but inversely associated with risk in overweight men. Further, prediagnostic IL‐6 was associated with time to prostate cancer progression/death among healthy weight prostate cancer cases (p_trend = 0.02). Adjusted hazard ratios were 1.73 (95% CI: 0.86, 3.51) comparing the highest to lowest IL‐6 level. Our study suggests that IL‐6 may potentially be involved in the development or progression of prostate cancer. © 2008 Wiley‐Liss, Inc.     

Associations of erythrocyte ω‐3 fatty acids with biomarkers of ω‐3 fatty acids and inflammation in breast tissue

There is increasing evidence that chronic inflammation is associated with increased breast cancer risk. Long‐chain omega‐3 polyunsaturated fatty acids (LCω‐3PUFA) may reduce circulating biomarkers of inflammation; however associations of blood LCω‐3PUFA with breast tissue LCω‐3PUFA and breast tissue biomarkers of inflammation are not well understood. We conducted a cross‐sectional analysis of breast tissue and blood samples from n = 85 women with no history of breast cancer, who underwent breast reduction surgery. Fatty acids of erythrocytes and undissected breast tissues were analyzed by gas chromatography; C‐reactive protein (CRP), interleukin (IL)–6 and IL‐8 in plasma and tissue were measured by ELISA. Multivariable‐adjusted regression models were used to estimate associations between erythrocyte LCω‐3PUFA and breast tissue biomarkers. Women in the highest erythrocyte LCω‐3PUFA tertile had LCω‐3PUFA concentrations in the breast 73% (95% CI: 31–128%; p trend < 0.0001) higher than women in the lowest tertile. Associations for each individual LCω‐3PUFA were similar in magnitude. No significant association was found for the shorter ω‐3 PUFA, α‐linolenic acid. Although compatible with no association, women in the highest tertile of erythrocyte eicosapentaenoic acid had a nonsignificant 32% (95% CI: ?23 to 62%) reduced breast tissue CRP. No correlation was observed between erythrocyte ω‐3 PUFA and tissue IL‐6 or IL‐8 concentrations. Our findings provide evidence that erythrocyte ω‐3 fatty acids are valid measures of breast tissue concentrations, and limited evidence that inverse associations from prospective epidemiologic studies of blood LCω‐3PUFA and breast cancer risk may be partly explained by reductions in breast tissue inflammation; however, these findings require replication.     

Adherence to Mediterranean diet and risk of cancer: A systematic review and meta‐analysis of observational studies

The aim of this research study was to meta‐analyze the effects of adherence to Mediterranean diet (MD) on overall cancer risk, and different cancer types. Literature search was performed using the electronic databases MEDLINE, SCOPUS and EMBASE until January 10, 2014. Inclusion criteria were cohort or case–control studies. Study specific risk ratios (RRs) were pooled using a random effect model by the Cochrane software package Review Manager 5.2. Twenty‐one cohort studies including 1,368,736 subjects and 12 case–control studies with 62,725 subjects met the objectives and were enclosed for meta‐analyses. The highest adherence to MD category resulted in a significantly risk reduction for overall cancer mortality/incidence (cohort; RR: 0.90, 95% CI 0.86–0.95, p < 0.0001; I² = 55%), colorectal (cohort/case–control; RR: 0.86, 95% CI 0.80–0.93, p < 0.0001; I² = 62%], prostate (cohort/case–control; RR: 0.96, 95% CI 0.92–0.99, p = 0.03; I² = 0%) and aerodigestive cancer (cohort/case–control; RR: 0.44, 95% CI 0.26–0.77, p = 0.003; I² = 83%). Nonsignificant changes could be observed for breast cancer, gastric cancer and pancreatic cancer. The Egger regression tests provided limited evidence of substantial publication bias. High adherence to a MD is associated with a significant reduction in the risk of overall cancer mortality (10%), colorectal cancer (14%), prostate cancer (4%) and aerodigestive cancer (56%).     

Anthropometric factors and ovarian cancer risk: A systematic review and nonlinear dose‐response meta‐analysis of prospective studies

In the World Cancer Research Fund/American Institute for Cancer Research report from 2007 the evidence relating body fatness to ovarian cancer risk was considered inconclusive, while the evidence supported a probably causal relationship between adult attained height and increased risk. Several additional cohort studies have since been published, and therefore we conducted an updated meta‐analysis of the evidence as part of the Continuous Update Project. We searched PubMed and several other databases up to 20th of August 2014. Summary relative risks (RRs) were calculated using a random effects model. The summary relative risk for a 5‐U increment in BMI was 1.07 (95% CI: 1.03–1.11, I² = 54%, n = 28 studies). There was evidence of a nonlinear association, p_nonlinearity < 0.0001, with risk increasing significantly from BMI～28 and above. The summary RR per 5 U increase in BMI in early adulthood was 1.12 (95% CI: 1.05–1.20, I² = 0%, p_{heterogeneity}= 0.54, n = 6), per 5 kg increase in body weight was 1.03 (95% CI: 1.02–1.05, I² = 0%, n = 4) and per 10 cm increase in waist circumference was 1.06 (95% CI: 1.00–1.12, I² = 0%, n = 6). No association was found for weight gain, hip circumference or waist‐to‐hip ratio. The summary RR per 10 cm increase in height was 1.16 (95% CI: 1.11–1.21, I² = 32%, n = 16). In conclusion, greater body fatness as measured by body mass index and weight are positively associated risk of ovarian cancer, and in addition, greater height is associated with increased risk. Further studies are needed to clarify whether abdominal fatness and weight gain is associated with risk.     

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.     

Serum insulin‐like,growth factor binding protein‐related protein 1 (IGFBP‐rP1) and endometrial cancer risk in Chinese women

Hyperinsulinemia and the metabolic syndrome confer increased risks of endometrial carcinoma. The roles of insulin, and, insulin‐like growth factor‐binding proteins (IGFBPs) in the etiology of endometrial carcinoma, remain unclear. We recruited 206 patients with endometrial carcinoma and 350 healthy women to a case–control study of fasting insulin and IGFBP‐related protein 1 (IGFBP‐rP1) in a Chinese tertiary centre. Patients with endometrial carcinoma had higher insulin concentrations (14.8 ± 16.7 vs. 8.1 ± 9.4 μU/mL; p < 0.001) and lower IGFBP‐rP1 levels (17.5 ± 17.2 vs. 22.4 ± 22.8 μg/L; p = 0.018) than controls. High insulin and IGFBP‐rP1 levels were both positively and negatively associated with endometrial cancer (odds ratio for the highest tertile versus the lowest tertile: insulin: 4.11; 95% CI = 2.61–6.47; IGFBP‐rP1: 0.38; 95% CI = 0.24–0.60). Logistic regression analysis confirmed the associations between endometrial carcinoma and fasting insulin or IGFBP‐rP1 after adjustments for age, BMI, serum glucose, cholesterol, triglycerides and high‐density lipoprotein cholesterol (odds ratio for the highest tertile versus the lowest tertile: insulin: 2.13; 95% CI = 1.30–3.49; IGFBP‐rP1: 0.57; 95% CI = 0.34–0.94). Hyperinsulinemia and high IGFBP‐rP1 levels confer altered risks for endometrial carcinoma.     

Calcium intake and colorectal adenoma risk: Dose‐response meta‐analysis of prospective observational studies

Evidence from randomized controlled trials suggests that calcium may protect against recurrence of colorectal adenomas, which could lead to the subsequent prevention of cancer. Yet the trials used only a large single dose and were of small sizes, and thus, knowledge of the dose‐response relationship and influence on high‐risk adenomas is limited. To address these issues, we conducted linear and nonlinear dose‐response meta‐analyses primarily based on prospective observational studies published up to July 2014 identified from PubMed and Embase. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated for total and supplemental calcium intake, respectively, using a random‐effects model. For total calcium intake, summary RR for each 300 mg/day increase was 0.95 (95% CI = 0.92–0.98; I² = 45%; eight studies with 11,005 cases; range of intake = 333–2,229 mg/day). Evidence of nonlinearity was indicated: approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.92 (95% CI = 0.89–0.94) at 1,000 mg/day and 0.87 (95% CI = 0.84–0.90) at 1,450 mg/day (p_nonlinearity < 0.01). Associations were stronger for high‐risk adenomas (≥1 cm in diameter, (tubulo)villous histology, dysplasia, or multiplicity): approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.77 (95% CI = 0.74–0.81) at 1,000 mg/day and reduced to 0.69 (95% CI = 0.66–0.73) at 1,450 mg/da (p_nonlinearity < 0.01). For supplemental calcium intake, summary RR of total adenoma risk for each 300 mg/day increase was 0.96 (95% CI = 0.93–0.99; I² = 0%; three studies with 4,548 cases; range of supplementation = 0–1,366 mg/day). In conclusion, calcium intake may continue to decrease the risk of adenomas, particularly high‐risk adenomas, over a wide range of calcium intake.     

Prediagnostic circulating inflammation markers and endometrial cancer risk in the prostate,lung, colorectal and ovarian cancer (PLCO) screening trial

Inflammation is proposed to increase risk of developing endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating inflammation markers and endometrial cancer risk. In a nested case‐control study within the PLCO Screening Trial we measured serum levels of 64 inflammation‐related biomarkers in 284 incident endometrial cancer cases and 284 matched controls. Using multivariable logistic regression inflammation markers were evaluated individually and combined into a cross‐validated inflammation score. Of 64 markers, 22 were associated with endometrial cancer risk at p < 0.05 and 17 of 22 markers remained associated after multiple testing corrections. After adjusting for BMI and estradiol, SERPINE1 [quartile(Q)4 vs. Q1 odds ratio (OR) (95% confidence interval (CI)), p trend = 2.43 (0.94–6.29), 0.03] and VEGFA [2.56 (1.52–4.30), 0.0002] were positively associated with endometrial cancer risk, while CCL3 [0.46 (0.27–0.77), 0.01], IL13 [0.55 (0.33–0.93), 0.01], IL21 [0.52 (0.31–0.87), 0.01], IL1B [0.51 (0.30–0.86), 0.01] and IL23 [0.60 (0.35–1.03), 0.02] were inversely associated with risk. We observed large differences in ORs across BMI‐inflammation score categories. Endometrial cancer risk was most pronounced among obese women with the highest inflammation score tertile (T) [10.25 (3.56–29.55) vs. normal BMI/T1]. Several inflammation markers were prospectively associated with endometrial cancer, including adipokines, pro‐ and anti‐inflammatory cytokines, angiogenic factors and acute phase proteins. Inverse associations with anti‐inflammatory markers (IL13, IL21), other inflammation markers/mediators (CCL3, IL1B, IL23), and a robust positive association between VEGFA and endometrial cancer risk were independent of BMI and estradiol, suggesting that these factors may influence risk through other mechanisms.     

Hepatitis C virus genotype 1b increases cumulative lifetime risk of hepatocellular carcinoma

The association between subtypes of hepatitis C virus (HCV) and risk of hepatocellular carcinoma (HCC) remained inconclusive and evaluated in both case–control and cohort studies. In the case–control study, 397 HCC cases from medical centers were compared with 410 community‐based non‐HCC controls. All of them were anti‐HCV‐seropositive, HBsAg‐seronegative with serum HCV RNA levels ≥1,000 IU/mL. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence interval (95% CI) of HCV subtype after controlling for other HCC risk factors. In the cohort study, 866 anti‐HCV‐seropositive individuals were followed from 1991 to 2008 to assess the long‐term HCC predictability of HCV subtypes. Newly developed HCC cases were ascertained by follow‐up health examinations and computerized linkage with national databases. The percentage of HCV 1b subtype was higher among HCC cases than controls (64 vs. 55%, p < 0.001). Participant infected with HCV 1b had a higher mean serum HCV RNA level (2.0 × 10⁶ IU/mL) than those infected with HCV non‐1b (1.2 × 10⁶ IU/mL, p < 0.001). The multivariate‐adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non‐1b was 1.43 (1.02–2.02). After the long‐term follow‐up, the cumulative lifetime (30–80 years old) HCC risk was 19.2 and 29.7% for patients infected with HCV non‐1b and 1b, respectively (p < 0.001). The multivariate‐adjusted hazard ratio (95% CI) was 1.85 (1.06–3.22) for HCV 1b compared to non‐1b. HCV subtype 1b, the most prevalent subtype in Taiwan, was associated with an increased HCC risk and a proactive clinical management is suggested for patients with HCV 1b.     

Prospective study of body mass index,physical activity and thyroid cancer

Increased body size and physical inactivity are positively related to risk of several cancers, but only few epidemiologic studies have investigated body‐mass index (BMI) and physical activity in relation to thyroid cancer. We examined the relations of BMI and physical activity to thyroid cancer in a prospective cohort of 484,326 United States men and women, followed from 1995/1996 to 2003. During 3,490,300 person‐years of follow‐up, we documented 352 newly incident cases of thyroid cancer. The multivariate relative risks (RR) of thyroid cancer for BMI values of 18.5–24.9 (reference), 25.0–29.9 and ≥30 kg m^?2 were 1.0, 1.27 and 1.39 [95% confidence interval (CI) = 1.05–1.85]. Adiposity predicted papillary thyroid cancers (RR comparing extreme BMI categories = 1.47; 95% CI = 1.03–2.10) and, based on small numbers, suggestively predicted follicular thyroid cancers (RR = 1.49; 95% CI = 0.79–2.82) and anaplastic thyroid cancers (RR = 5.80; 95% CI = 0.99–34.19). No relation with BMI was noted for medullary thyroid cancers (RR = 0.97; 95% CI = 0.27–3.43). The positive relation of BMI to total thyroid cancer was evident for men but not for women. However, the test of interaction (p = 0.463) indicated no statistically significant gender difference. Physical activity was unassociated with thyroid cancer. The RRs of total thyroid cancer for low (reference), intermediate, and high level of physical activity were 1.0, 1.01 and 1.01 (95% CI = 0.76–1.34, p for trend = 0.931), respectively. Our results support an adverse effect of adiposity on risk for developing total and papillary, and possibly follicular thyroid cancers. Based on only 15 cases, adiposity was unrelated to medullary thyroid cancers. Physical activity was unrelated to total thyroid cancer.     

Effects of α‐tocopherol and β‐carotene supplementation on cancer incidence and mortality: 18‐Year postintervention follow‐up of the Alpha‐Tocopherol,Beta‐Carotene Cancer Prevention Study

In the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study among 29,133 Finnish male smokers aged 50–69 years, daily α‐tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas β‐carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the postintervention effects of α‐tocopherol and β‐carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplement had significant effects on post‐trial cancer incidence. Relative risk (RR) for lung cancer (n = 2,881) was 1.04 (95% confidence interval [CI], 0.96–1.11) among β‐carotene recipients compared with nonrecipients. For prostate cancer (n = 2,321), RR was 0.97 (95% CI, 0.89–1.05) among α‐tocopherol recipients compared with nonrecipients with the preventive effect of α‐tocopherol continuing ～8 years postintervention. Body mass index significantly modified the effect of α‐tocopherol on prostate cancer (p for interaction = 0.01) RR 1.00 (95% CI, 0.88–1.14) in normal‐weight men, 0.87 (95% CI, 0.77–0.98) in overweight men, and 1.25 (95% CI, 1.01–1.55) in obese men. The post‐trial relative mortality (based on 16,686 deaths) was 1.02 (95% CI, 0.98–1.05) for α‐tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99–1.05) for β‐carotene recipients compared with nonrecipients. α‐Tocopherol decreased post‐trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70–0.99), whereas β‐carotene increased it (RR, 1.20; 95% CI, 1.01–1.42). In conclusion, supplementation with α‐tocopherol and β‐carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate‐dose α‐tocopherol on prostate cancer continued several years post‐trial and resulted in lower prostate cancer mortality.     

High serum interleukin‐6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B

Increased interleukin‐6 (IL‐6) production is implicated in the pathogenesis of hepatocellular carcinoma (HCC) in animal models. Although previous studies showed that HCC patients had higher serum IL‐6 level at the time of diagnosis, it is unclear if the cytokine contributes to the development of HCC or is just a reaction to cancer. To address this question, we performed a nested case‐control study. Consecutive chronic hepatitis B patients were recruited from 1997 to 2000 and followed till 2008. Profiling of 27 cytokines, chemokines and growth factors was performed at baseline, date of peak alanine aminotransferase (ALT) level and the last visit. Thirty‐seven patients developed HCC at a median follow‐up of 62 months (interquartile range: 41–110). Serum IL‐6 was higher in patients with HCC than controls both during peak ALT and at the last visit (both p = 0.02). Patients with IL‐6 above 7 pg/ml during peak ALT had increased risk of HCC or death (adjusted hazard ratio 3.0; 95% confidence interval 1.2, 7.8; p = 0.02). The sensitivity, specificity, positive and negative predictive values of this cutoff to predict future HCC development were 70%, 73%, 72% and 71%, respectively. Combination of IL‐6 and AFP improved the sensitivity in diagnosing HCC or predicting future HCC development. In conclusion, high serum IL‐6 level predates the development of HCC in chronic hepatitis B patients, and has moderate accuracy in predicting future cancer. This may assist clinicians in selecting high‐risk patients for HCC surveillance program. © 2009 UICC     

A prospective investigation of serum 25‐hydroxyvitamin D and risk of lymphoid cancers

Studies indicate that higher sun exposure, especially in the recent past, is associated with reduced risk of non‐Hodgkin lymphoma (NHL). Ultraviolet radiation‐derived vitamin D may be protective against lymphomagenesis. We examined the relationship between prediagnostic serum 25‐hydroxyvitamin D (25(OH)D) and lymphoid cancer risk in a case–control study nested within the Alpha‐Tocopherol Beta‐Carotene Cancer Prevention Study cohort (1985–2002) of 29,133 Finnish male smokers (ages 50–69). We identified 270 incident lymphoid cancer cases and matched them individually with 538 controls by birth‐year and month of fasting blood draw at baseline. In conditional logistic regression models for 10 nmol/L increments or tertile comparisons, serum 25(OH)D was not associated with the risk of overall lymphoid cancers, NHL (n = 208) or multiple myeloma (n = 41). Odds ratios (OR) for NHL for higher tertiles were 0.75 (95% confidence interval (CI), 0.50, 1.14) and 0.82 (95% CI, 0.53, 1.26). The 25(OH)D‐NHL association, however, differed by follow‐up duration at diagnosis. Cases diagnosed less than 7 years from the baseline showed an inverse association (OR for highest vs. lowest tertile = 0.43; 95% CI: 0.23, 0.83; p for trend = 0.01), but not later diagnoses (OR = 1.52; 95% CI: 0.82, 2.80; p for trend = 0.17). The inverse association found for close exposure to diagnosis was not confounded by other risk factors for lymphoma or correlates of 25(OH)D. Although our findings suggest that circulating 25(OH)D is not likely associated with overall lymphoid cancer, they indicate a potentially protective effect on short‐term risk of NHL. © 2008 Wiley‐Liss, Inc.     

Obesity and incidence of lung cancer: A meta‐analysis

To date, the relationship between obesity and the incidence of lung cancer remains unclear and inconclusive. Thus, we conducted a meta‐analysis of published studies to provide a quantitative evaluation of this association. Relevant studies were identified through PubMed and EMBASE databases from 1966 to December 2011, as well as through the reference lists of retrieved articles. A total of 31 articles were included in this meta‐analysis. Overall, excess body weight (body mass index, BMI ≥ 25 kg/m²) was inversely associated with lung cancer incidence (relative risk, RR = 0.79; 95% confidence interval, CI: 0.73–0.85) compared with normal weight (BMI = 18.5‐24.9 kg/m²). The association did not change with stratification by sex, study population, study design, and BMI measurement method. However, when stratified by smoking status, the inverse association between excess body weight and lung cancer incidence in current (RR = 0.63, 95% CI: 0.57–0.70) and former (RR = 0.73, 95% CI: 0.58–0.91) smokers was strengthened. In non‐smokers, the association was also statistically significant (RR = 0.83, 95% CI: 0.70–0.98), although the link was weakened to some extent. The stratified analyses also showed that excess body weight was inversely associated with squamous cell carcinoma (RR = 0.68, 95% CI: 0.58–0.80) and adenocarcinoma (RR = 0.79, 95% CI: 0.65–0.96). No statistically significant link was found between excess body weight and small cell carcinoma (RR = 0.99, 95% CI: 0.66–1.48). The results of this meta‐analysis indicate that overweight and obesity are protective factors against lung cancer, especially in current and former smokers.     

Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH‐AARP Diet and Health Study

During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health‐American Association of Retired Persons (NIH‐AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50–71 years in 1995–1996. Dietary intakes were assessed using a 124‐item food frequency questionnaire. During an average of 7 years of follow‐up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk [RR] for the highest quintile versus lowest quintile RR = 2.28, 95% confidence interval [CI]: 1.29–4.041; p‐trend <0.001); however, we observed no trend with intake among women (p‐trend = 0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95% CI: 1.09–4.05; p‐trend = 0.05) and follicular thyroid cancer (RR = 3.42; 95% CI: 1.03–11.4; p‐trend = 0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR = 2.74; 95%CI: 0.86–8.77; p‐trend = 0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted.     

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.     

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     

Association between adult weight gain and colorectal cancer: A dose–response meta‐analysis of observational studies

This study investigated the association between adult weight gain and risk of colorectal cancer (CRC). Using terms related to weight gain and CRC, we searched PubMed, Embase and Web of Science for relevant studies published before June 2014. Two evaluators independently selected studies according to the selection criteria, and eight studies were included (three case–control and five cohort studies). Summary estimates were obtained using fixed‐ or random‐effects models. The relative risk (RR) of the association between adult weight gain and CRC was 1.25 (95% confidence interval [CI], 1.10–1.43); the RR was 1.30 (95% CI, 1.14–1.49) for colon cancer (CC) and 1.27 (95% CI, 1.02–1.58) for rectal cancer (RC) for the highest versus lowest category. For every 5‐kg increase in adult weight, the risk increased by 5% (RR, 1.05; 95% CI, 1.02–1.09) for CRC, 6% (RR, 1.06; 95% CI, 1.02–1.11) for CC and 6% (RR, 1.06; 95% CI, 1.03–1.08) for RC. The subgroup analyses showed a positive association between adult weight gain and risk of CRC only in men, and the RR was 1.65 (95% CI, 1.42–1.92) for the highest versus lowest category of adult weight gain and 1.10 (95% CI, 1.06–1.15) for a 5‐kg increase in adult weight. In conclusion, there is evidence that adult weight gain is associated with an increased risk of CRC. However, the positive association between adult weight gain and risk of CRC is stronger among men than among women.     

Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality

BACKGROUND.

Adiposity has been linked inconsistently with prostate cancer, and few studies have evaluated whether such associations vary by disease aggressiveness.

METHODS.

The authors prospectively examined body mass index (BMI) and adult weight change in relation to prostate cancer incidence and mortality in 287,760 men ages 50 years to 71 years at enrollment (1995–1996) in the National Institutes of Health‐AARP Diet and Health Study. At baseline, participants completed questionnaires regarding height, weight, and cancer screening practices, including digital rectal examinations and prostate‐specific antigen tests. Cox regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (95% CIs).

RESULTS.

In total, 9986 incident prostate cancers were identified during 5 years of follow‐up, and 173 prostate cancer deaths were ascertained during 6 years of follow‐up. In multivariate models, higher baseline BMI was associated with significantly reduced total prostate cancer incidence, largely because of the relationship with localized tumors (for men in the highest BMI category [≥40 kg/m²] vs men in the lowest BMI category [<25 kg/m²]: RR, 0.67; 95% CI, 0.50–0.89; P = .0006). Conversely, a significant elevation in prostate cancer mortality was observed at higher BMI levels (BMI <25 kg/m²: RR, 1.0 [referent group]; BMI 25–29.9 kg/m²: RR, 1.25; 95% CI, 0.87–1.80; BMI 30–34.9 kg/m²: RR, 1.46; 95% CI, 0.92–2.33; and BMI ≥35 kg/m²: RR, 2.12; 95% CI, 1.08–4.15; P = .02). Adult weight gain from age 18 years to baseline also was associated positively with fatal prostate cancer (P = .009), but not with incident disease.

CONCLUSIONS.

Although adiposity was not related positively to prostate cancer incidence, higher BMI and adult weight gain increased the risk of dying from prostate cancer. Cancer 2007. Published 2007 by the American Cancer Society.     

Isoflavone consumption and subsequent risk of hepatocellular carcinoma in a population‐based prospective cohort of Japanese men and women

The incidence of hepatocellular carcinoma (HCC) is much higher in men than in women. Several experiment and epidemiological studies have suggested that estrogen might play an inhibitory role in the development of HCC. Because isoflavones have a similar structure as 17β‐estradiol and appear to have an anti‐estrogenic effect in women and estrogenic effect in men, we hypothesized that the effect of isoflavones on HCC differs by sex. We investigated the association between isoflavones (genistein and daidzein) and soy products and HCC in Japan in a population‐based prospective study in 19,998 Japanese (7,215 men and 12,783 women) aged 40–69 years. During 11.8 years of follow‐up, 101 subjects (69 men and 32 women) were newly diagnosed with HCC. Case patients were grouped according to consumption of isoflavones and soy products and stratified by hepatitis virus infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC were calculated by Cox proportional‐hazards modeling. In women, genistein and daidzein were dose‐dependently associated with an increased risk of HCC, with multivariable HRs for the highest versus lowest tertile of 3.19 (95%CI = 1.13–9.00, p_trend = 0.03) and 3.90 (95% CI = 1.30–11.69, p_trend = 0.01), respectively. No association between isoflavones and HCC was observed in men. These results persisted when analysis was restricted to subjects positive for either or both hepatitis C and B virus. In conclusion, isoflavone consumption may be associated with an increased risk of HCC in women. Women with hepatitis virus infection may be advised to abstain from isoflavone consumption. Further studies are warranted to confirm these findings. © 2008 Wiley‐Liss, Inc.