Intake of meat mutagens and risk of prostate cancer in a cohort of U.S. health professionals

BACKGROUND: Evidence relating heterocyclic aromatic amines (HCA), associated with high-temperature cooking methods, to prostate cancer risk is inconsistent Methods: In a large US cohort study, intakes of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and a meat-derived mutagenicity index (MDM) were assessed using a cooking method questionnaire administered in 1996. Until 2010, 2,770 prostate cancer cases were observed among 26,030 participants. RESULTS: Intake of PhIP from red meat was statistically significantly associated with total prostate cancer risk (top vs. bottom quintile HR=1.18, 95% CI 1.03-1.35), but not other HCAs (MeIQx, 1.12, 0.98-1.27, PhIP from white meat, 1.07, 0.94-1.21, DiMeIQx, 1.09, 0.97-1.21) or MDM (1.13, 1.00-1.28). For high grade (Gleason sum 7 with pattern 4+3 and Gleason sum 8-10, n=483 cases) and advanced cancers (n=281), we only observed positive associations for PhIP from red meat (top vs. bottom quintile: high grade: HR=1.44, 95% CI 1.04-1.98, p-trend=0.03; advanced: HR=1.50, 95% 0.99-2.26; p-trend=0.12), but associations for advanced cancers did not reach statistical significance. Observed associations remained similar after adjustment for total, unprocessed or processed red meat intake. CONCLUSION: Observed positive associations between PhIP intake from red meat and prostate cancer, particularly high-grade and possibly also advanced prostate cancer need to be confirmed in other studies. IMPACT: Results do not provide strong evidence that HCAs increase risk of prostate cancers

Prediagnostic adult body mass index change and esophageal adenocarcinoma survival

Background: We examined whether body mass index (BMI) changes in adulthood, prior to disease onset, are associated with overall survival among esophageal adenocarcinoma patients. Methods: We included 285 histologically confirmed patients with a complete baseline BMI questionnaire. Using extended Cox regression models, we obtained adjusted hazard ratios (HRs) for the associations between overall survival and BMI at diagnosis, BMI 6 months before diagnosis, self-reported average adult BMI, and ΔBMI (BMI 6 months before diagnosis minus average adult BMI), categorized into tertiles 25 and <35 kg/m2 was associated with better overall survival. Compared to patients with stable BMI in adulthood, patients who gained BMI throughout adulthood had 1.68 times the all-cause hazard of death (95% CI: 1.17-2.43; P <.01), independent of diagnosis BMI and percent weight loss 6 months before diagnosis. Compared to patients with average adult BMI < 27.5 who maintained stable adult BMI, patients with average adult BMI ≥ 27.5 kg/m2 who gained BMI had the worst survival (HR = 3.05; 95% CI 1.62-5.72; P <.01). Conclusion: Body mass index gain in adulthood is associated with poor overall survival, and maintaining a normal body weight throughout adulthood is associated with the best overall survival among esophageal adenocarcinoma patients, independent of BMI at diagnosis

Association Between Midlife Obesity and Kidney Function Trajectories: The Atherosclerosis Risk in Communities (ARIC) Study

Rationale &amp; Objective: Obesity has been related to risk for chronic kidney disease. However, the associations of different measures of midlife obesity with long-term kidney function trajectories and whether they differ by sex and race are unknown. Study Design: Observational study. Setting &amp; Participants: 13,496 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Predictors: Midlife obesity status as measured by body mass index (BMI), waist-to-hip ratio, and predicted percent fat at baseline. Outcomes: Estimated glomerular filtration rate (eGFR) calculated using serum creatinine level measured at 5 study visits, and incident kidney failure with replacement therapy (KFRT). Analytical Approach: Mixed models with random intercepts and random slopes for eGFR. Cox proportional hazards models for KFRT. Results: Baseline mean age was 54 years, median eGFR was 103 mL/min/1.73 m2, and median BMI was 27 kg/m2. Over 30 years of follow-up, midlife obesity measures were associated with eGFR decline in White and Black women but not consistently in men. Adjusted for age, center, smoking, and coronary heart disease, the differences in eGFR slope per 1-SD higher BMI, waist-to-hip ratio, and predicted percent fat were 0.09 (95% CI, −0.18 to 0.36), −0.25 (95% CI, −0.50 to 0.01), and −0.14 (95% CI, −0.41 to 0.13) mL/min/1.73 m2 per decade for White men; −0.91 (95% CI, −1.15 to −0.67), −0.82 (95% CI, −1.06 to −0.58), and −1.02 (95% CI, −1.26 to −0.78) mL/min/1.73 m2 per decade for White women; −0.70 (95% CI, −1.54 to 0.14), −1.60 (95% CI, −2.42 to −0.78), and −1.24 (95% CI, −2.08 to −0.40) mL/min/1.73 m2 per decade for Black men; and −1.24 (95% CI, −2.08 to −0.40), −1.50 (95% CI, −2.05 to −0.95), and −1.43 (95% CI, −2.00 to −0.86) mL/min/1.73 m2 per decade for Black women. Obesity indicators were independently associated with risk for KFRT for all sex-race groups except White men. Limitations: Loss to follow-up during 3 decades of follow-up with 5 eGFR assessments. Conclusions: Obesity status is a risk factor for future decline in kidney function and development of KFRT in Black and White women, with less consistent associations among men

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Postprandial duration influences the association of insulin-related dietary indexes and plasma C-peptide concentrations in adult men and women

BACKGROUND: The dietary insulin index (II) directly quantifies dietary effects on postprandial insulin secretion, whereas the empirical dietary index for hyperinsulinemia (EDIH), based on fasting C-peptide concentrations, is primarily reflective of insulin resistance. How these scores are related to nonfasting C-peptide in cohort studies has not been examined. OBJECTIVE: We investigated the extent to which EDIH and II scores predict plasma C-peptide concentrations, in cross-sectional analyses by postprandial duration at blood collection from 1 to ≥15 h. METHODS: Both EDIH and II scores were calculated from food-frequency questionnaire data reported by 3964 men in the Health Professionals Follow-up Study (1993-1995) and 6215 women in the Nurses' Health Study (1989-1990) who were not diabetic. We constructed 12 multivariable-adjusted linear regression models separately in men and women, by postprandial duration, to calculate relative differences and absolute values of plasma C-peptide concentrations in dietary index quintiles. RESULTS: In both men and women, C-peptide concentrations were elevated 1-2 h after eating and declined with increasing postprandial duration. In men, percent differences in C-peptide concentration in the highest compared with lowest dietary index quintile were: EDIH: 0-1 h: 50%; 2 h: 22%; 14 h: 14%; ≥15 h: 30% (all P-trend< 0.05). II: 0-1 h: 19% (P-trend = 0.09); 2 h: 3% (P-trend = 0.09); 14 h: -6% (P-trend = 0.17); ≥15 h: -15% (P-trend = 0.02). Corresponding results among women were: EDIH: 0-1 h: 29% (P-trend = 0.002); 2 h: 33% (P-trend = 0.009); 14 h: 44% (P-trend < 0.0001); ≥15 h: 40% (P-trend < 0.0001). II: 0-1 h: -12% (P-trend = 0.09); 2 h: 17% (P-trend = 0.09); 14 h: -14% (P-trend = 0.009); ≥15 h: -3% (P-trend = 0.37). CONCLUSION: The EDIH was superior to the II in predicting both fasting and nonfasting C-peptide concentrations, suggesting that the EDIH may be better in assessing dietary effects of hyperinsulinemia on disease risk in adult men and women

Lifestyle after Colorectal Cancer Diagnosis in Relation to Survival and Recurrence: A Review of the Literature

Contains fulltext : 182791.pdf (Publisher’s version ) (Open Access)Purpose of Review: This review summarizes the evidence regarding diet, physical activity, smoking, and body composition after colorectal cancer (CRC) diagnosis in relation to all-cause and CRC-specific mortality and disease recurrence and gives suggestions for future research directions. Recent Findings: Overall, this review suggests that some, albeit not all, of the well-known modifiable risk factors for cancer incidence might also be associated with CRC survival. CRC prognosis appears to be worse with increased physical inactivity, smoking, or being underweight after CRC diagnosis. Emerging evidence suggests that diets associated with a positive energy balance, e.g., high consumption of sugar-sweetened beverages, may negatively impact survival in CRC survivors. In contrast, there is currently little evidence to support the recommendation to limit red and processed meat or alcohol intake after CRC diagnosis. Whether being overweight and obese after CRC diagnosis improves or worsens CRC prognosis remains controversial and may depend on the measure used to assess body fatness. Summary: Further research on post-diagnosis lifestyle patterns is needed to understand the multifactorial influence on CRC prognosis. Disease recurrence and the development of comorbidities should be included as key outcomes in future studies and lifestyle should preferably be repeatedly measured

Prediagnostic plasma IGFBP-1, IGF-1 and risk of prostate cancer

Insulin-like growth factor (IGF)-1 is associated with a higher risk of prostate cancer. IGF-binding protein (IGFBP)-1, a marker for insulin activity, also binds IGF-1 and inhibits its action. Data on IGFBP-1 and prostate cancer risk are sparse and whether the IGF and insulin axes interact to affect prostate cancer carcinogenesis is unknown. We evaluated the independent and joint influence of prediagnostic plasma levels of IGFBP-1 (fasting) and IGF-1 on risk of prostate cancer among 957 cases and 1,021 controls with fasting levels of IGFBP-1 and 1,709 cases and 1,778 controls with IGF-1 nested within the Health Professionals Follow-up Study. Unconditional logistic regression adjusting for matching factors was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Higher prediagnostic fasting IGFBP-1 levels were associated with lower risk of prostate cancer (highest vs. lowest quartile OR = 0.67, 95% CI 0.52-0.86, ptrend  = 0.003), which remained similar after adjusting for IGF-1. Prediagnostic IGF-1 was associated with increased risk of prostate cancer (highest vs. lowest quartile OR = 1.28, 95% CI = 1.05-1.56, ptrend  = 0.01). The associations with each marker were primarily driven by lower-grade and non-advanced prostate cancer. Being low in IGFBP-1 and high in IGF-1 did not confer appreciable additional risk (pinteraction  = 0.42). In summary, prediagnostic fasting IGFBP-1 may influence prostate cancer carcinogenesis. Being low in IGFBP-1 or high in IGF-1 is sufficient to elevate the risk of prostate cancer

Early life body fatness and risk of colorectal cancer in U.S. women and men: results from two large cohort studies

Background: The association between body fatness before adulthood and later risk of colorectal cancer remains unclear. We hypothesized that, independent of adult body fatness, early life body fatness would be associated with a higher risk of developing colorectal cancer. Methods: We assessed body fatness during childhood and adolescence using a validated 9-level somatotype and inquired body weight in young adulthood in the Nurses' Health Study and Health Professionals Follow-up Study. We used the Cox proportional hazard regression modeling to estimate relative risks [RR, 95% confidence intervals (CI)] adjusting for adult body mass index (BMI) and other known colorectal cancer risk factors. Results: We identified 2,100 incident colorectal cancer cases (1,292 in women and 808 in men) during 22 years of follow-up. Among women, the RR (95% CI) for childhood body fatness of level 5 or higher versus level 1 was 1.28 (1.04-1.58; Ptrend = 0.08) and for adolescent body fatness, it was 1.27 (1.01-1.60; Ptrend = 0.23). The corresponding RRs for men were 1.04 (0.82-1.31; Ptrend = 0.48) and 0.98 (0.75-1.27; Ptrend = 0.20), respectively. Results were generally similar across anatomic subsites within the colorectum. In addition, the RRs comparing BMI categories >/=27.5 to <19 kg/m2 were 1.44 (1.06-1.95, at age 18; Ptrend = 0.009) for women and 1.18 (0.84-1.65, at age 21; Ptrend = 0.57) for men. Conclusion: Increased body fatness in early life, independent of adult obesity, might be a risk factor for colorectal cancer in women, but we observed a weaker association in men. Impact: Our findings support the growing evidence that early life body fatness affects the risk of colorectal cancer many decades later

Plasma Concentrations of Long Chain N-3 Fatty Acids in Early and Mid-Pregnancy and Risk of Early Preterm Birth

Background: Fish oil supplementation has been shown to delay spontaneous delivery, but the levels and clinical significance remain uncertain. We examined the association between plasma fatty acids quantified in pregnancy and subsequent risk of early preterm birth. Methods: In a case-control design nested in the Danish National Birth Cohort, we identified 376 early preterm cases (<34 gestational weeks, excluding preeclampsia cases) and 348 random controls. Plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA% of total fatty acids), were measured twice in pregnancy, at gestation weeks 9 and 25 (medians). Odds ratios and 95% confidence intervals (CI's) for associations between EPA+DHA and early preterm risk were estimated by logistic regression, adjusted for the woman's age, height, pre-pregnancy BMI, parity, smoking, and socioeconomic factors. Hypotheses and analytical plan were defined and archived a priori. Findings: Analysis using restricted cubic splines of the mean of 1st and 2nd sample measurements showed a strong and significant non-linear association (p < 0.0001) in which the risk of early preterm birth steeply increased when EPA+DHA concentrations were lower than 2% and flattened out at higher levels. Women in the lowest quintile (EPA+DHA < 1.6%) had 10.27 times (95% confidence interval 6.80–15.79, p < 0.0001) increased risk, and women in the second lowest quintile had 2.86 (95% CI 1.79–4.59, p < 0.0001) times increased risk, when compared to women in the three aggregated highest quintiles (EPA+DHA ≥ 1.8%). Interpretation: Low plasma concentration of EPA and DHA during pregnancy is a strong risk factor for subsequent early preterm birth in Danish women. Keywords: Early preterm birth, Long chained n-3 fatty acids, Biomarkers, Prospective study, Danish National Birth Cohor