Moderate alcohol consumption, types of beverages and drinking pattern with cardiometabolic biomarkers in three cohorts of US men and women.

Underlying mechanisms of the inverse relationship between moderate alcohol consumption and cardiometabolic disorders are unclear. Modification by types of alcoholic beverages consumed and drinking pattern remains understudied. We aimed to provide insight into the mechanisms by examining 14 insulinemic/glycemic, inflammatory and lipid markers. We used cross-sectional data from 15,436 women in the Nurses' Health Study, 19,318 women in the Nurses' Health Study II, and 6872 men in the Health Professionals Follow-up Study. Multivariable linear regression was used to estimate the percentage differences in biomarker concentrations according to alcohol intakes. The average alcohol intake in the combined cohort was 3.3 servings/week. We found a 1 serving/d increment in alcohol intake (14 g ethanol, 44 ml liquor or 355 ml beer or 118 ml wine per day) was associated with a 0.6% lower level of HbA1c, 1.7-3.6% lower proinflammatory markers and 4.2% higher adiponectin, as well as 7.1% higher HDL-cholesterol and 2.1% lower triglyceride with a significant linear trend. Wine, especially red wine, was associated with lower inflammation in particular. Beer had weaker favorable to null associations with blood lipids and adiponectin. Liquor was associated with higher C-peptide and interleukin-6, yet equally associated with lower HbA1c and higher HDL-cholesterol as other beverages. Drinking 3 days or more per week was related to a better biomarker profile than nonregular drinking independent of intake levels. Drinking appeared to have similar associations irrespective whether done with meals or not. Our data indicated moderate alcohol intake, especially if consumed from wine and done regularly, was associated with favorable profiles of insulinemic/glycemic and inflammatory markers and blood lipids.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations throughout the life course and risk of colorectal cancer precursors.

BACKGROUND: Despite the increasing incidence in colorectal cancer (CRC) among the young population, the involvement of modifiable early-life exposures is understudied. METHODS: We prospectively investigated the association of lifestyle score, which measures adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations, in adolescence and adulthood with risk of CRC precursors in 34,509 women enrolled in the Nurses' Health Study II. Participants reported adolescent diet in 1998 and subsequently underwent at least one lower gastrointestinal endoscopy between 1999 and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression for clustered data. RESULTS: During follow-up (1998-2015), 3036 women had at least one adenoma, and 2660 had at least one serrated lesion. In multivariable analysis, per unit increase in adolescent WCRF/AICR lifestyle score was not associated with risk of total adenoma or serrated lesions, in contrast to adult WCRF/AICR lifestyle score (OR = 0.92, 95% CI: 0.87-0.97, Ptrend = 0.002 for total adenoma; and OR = 0.86, 95% CI: 0.81-0.92, Ptrend < 0.001 for total serrated lesions). CONCLUSION: Adherence to the 2018 WCRF/AICR recommendations during adulthood but not during adolescence was associated with a lower risk of CRC precursors.

Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in men.

BACKGROUND: Gut microbial dysbiosis contributes to colorectal cancer (CRC) pathogenesis, possibly mediated in part by increased intestinal permeability to endotoxin lipopolysaccharide (LPS), microbial translocation, and subsequent endotoxemia and inflammation. However, epidemiologic evidence linking circulating markers of microbial translocation with CRC risk is limited. METHODS: We conducted a prospective, nested case-control study of 261 incident CRC cases and 261 controls (matched on age and time of blood draw) among 18,159 men with pre-diagnostic blood specimens in the Health Professionals Follow-Up Study (1993-2009). We examined three complementary markers of microbial translocation and host response to bacteria, including LPS-binding protein (LBP), soluble CD14 (sCD14), and endotoxincore antibody (EndoCAb) immunoglobulin M (IgM), with subsequent risk of CRC. Unconditional logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). FINDINGS: Pre-diagnostic circulating levels of sCD14 were associated with a higher risk of incident CRC. Compared to men in the lowest quartile, the multivariable OR was 1.90 (95% CI, 1.13-3.22) for men in the highest quartile (OR per standard deviation [SD] increase, 1.28; 95%CI 1.06-1.53; Ptrend = 0.01). This positive association remained similar after adjusting for C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptor-2, and within strata of putative CRC risk factors. We also observed a suggestive inverse association between EndoCAb IgM and risk of CRC (OR per SD increase, 0.84; 95%CI 0.69-1.02; Ptrend = 0.09). INTERPRETATION: Microbial translocation and host response to bacteria, as reflected by sCD14, is associated with risk of incident CRC in men. FUNDING: US National Institutes of Health.

Fructose consumption from different food sources and cardiometabolic biomarkers: cross-sectional associations in US men and women.

BACKGROUND: Previous studies on the relationship between fructose intake and cardiometabolic biomarkers have yielded inconsistent results, and the metabolic effects of fructose are likely to vary across food sources such as fruit versus sugar-sweetened beverages (SSB). OBJECTIVES: We aimed to examine associations of fructose from 3 major sources (SSB, fruit juice, and fruit) with 14 insulinemic/glycemic, inflammatory, and lipid markers. METHODS: We utilized cross-sectional data from 6858 men in the Health Professionals Follow-up Study, 15,400 women in NHS, and 19,456 women in NHSII who were free of type 2 diabetes, CVDs, and cancer at blood draw. Fructose intake was assessed via a validated FFQ. Multivariable linear regression was used to estimate the percentage differences of biomarker concentrations according to fructose intake. RESULTS: We found a 20 g/d increase in total fructose intake was associated with 1.5%- 1.9% higher concentrations of proinflammatory markers plus 3.5% lower adiponectin, as well as 5.9% higher TG/HDL cholesterol ratio. Unfavorable profiles of most biomarkers were only associated with fructose from SSB and juice. In contrast, fruit fructose was associated with lower concentrations of C-peptide, CRP, IL-6, leptin, and total cholesterol. Substituting 20 g/d fruit fructose for SSB fructose was associated with 10.1% lower C-peptide, 2.7%-14.5% lower proinflammatory markers and 1.8%-5.2% lower blood lipids. CONCLUSIONS: Beverage fructose intake was associated with adverse profiles of multiple cardiometabolic biomarkers.

Total calcium, dairy foods and risk of colorectal cancer: a prospective cohort study of younger US women.

BACKGROUND: Although colorectal cancer (CRC) incidence is declining among adults aged ≥65 years, CRC incidence in younger adults has been rising. The protective role of calcium in colorectal carcinogenesis has been well established, but evidence is lacking on whether the association varies by age at diagnosis. We investigated the association between total calcium intake and risk of overall CRC and CRC before age 55 years. METHODS: In the Nurses' Health Study II (1991-2015), 94 205 women aged 25-42 years at baseline were included in the analysis. Diet was assessed every 4 years through validated food frequency questionnaires. Multivariable-adjusted hazard ratios (HRs) and 95% CIs for CRC were estimated using the Cox proportional hazards model. RESULTS: We documented 349 incident CRC cases during 2 202 604 person-years of follow-up. Higher total calcium intake was associated with a reduced risk of CRC. Compared with those with <750 mg/day of total calcium intake, the HR of CRC was 0.61 (95% CI, 0.38-0.97) for those who consumed ≥1500 mg/day (P for trend = 0.01). The HR per 300 mg/day increase was 0.85 (95% CI, 0.76-0.95). There was a suggestive inverse association between total calcium intake and CRC before age 55 years (HR per 300 mg/day increase, 0.87; 95% CI, 0.75-1.00), suggesting the importance of calcium intake in the younger population. CONCLUSIONS: In a cohort of younger women, which reflects the birth cohorts, time periods and age ranges paralleling the recent rise in CRC, higher calcium intake was associated with a decreased risk of CRC.

Sugar-sweetened beverage and sugar consumption and colorectal cancer incidence and mortality according to anatomic subsite.

BACKGROUND: Recent preclinical research strongly suggests that dietary sugars can enhance colorectal tumorigenesis by direct action, particularly in the proximal colon that unabsorbed fructose reaches. OBJECTIVES: We aimed to examine long-term consumption of sugar-sweetened beverages (SSBs) and total fructose in relation to incidence and mortality of colorectal cancer (CRC) by anatomic subsite. METHODS: We followed 121,111 participants from 2 prospective US cohort studies, the Nurses' Health Study (1984-2014) and Health Professionals Follow-Up Study (1986-2014), for incident CRC and related death. Cox proportional hazards regression was used to compute HRs and 95% CIs. RESULTS: During follow-up, we documented 2733 incident cases of CRC with a known anatomic location, of whom 901 died from CRC. Positive associations of SSB and total fructose intakes with cancer incidence and mortality were observed in the proximal colon but not in the distal colon or rectum (Pheterogeneity ≤ 0.03). SSB consumption was associated with a statistically significant increase in the incidence of proximal colon cancer (HR per 1-serving/d increment: 1.18; 95% CI: 1.03, 1.34; Ptrend = 0.02) and a more pronounced elevation in the mortality of proximal colon cancer (HR: 1.39; 95% CI: 1.13, 1.72; Ptrend = 0.002). Similarly, total fructose intake was associated with increased incidence and mortality of proximal colon cancer (HRs per 25-g/d increment: 1.18; 95% CI: 1.03, 1.35; and 1.42; 95% CI: 1.12, 1.79, respectively). Moreover, SSB and total fructose intakes during the most recent 10 y, rather than those from a more distant period, were associated with increased incidence of proximal colon cancer. CONCLUSIONS: SSB and total fructose consumption were associated with increased incidence and mortality of proximal colon cancer, particularly during later stages of tumorigenesis.

Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors.

BACKGROUND & AIMS: Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50. METHODS: We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratios (ORs) and 95% CIs for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model. RESULTS: We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend = .01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n = 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n = 1,878). CONCLUSIONS: In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.

The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors.

BACKGROUND & AIMS: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. METHODS: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10-1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50. CONCLUSIONS: Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.

Association of sedentary patterns with body fat distribution among US children and adolescents: a population-based study.

BACKGROUND/OBJECTIVES: Children and adolescents spend a substantial amount of time being sedentary. The impact of prolonged sedentary patterns on fat distribution has not been elucidated especially in the context of physical activity level. Our objective is to examine the independent and joint associations of prolonged sedentary patterns and physical activity level with fat distribution among children and adolescents. SUBJECTS/METHODS: This included US children (8-11 years) and adolescents (12-19 years) from the National Health and Nutrition Examination Survey 2003-2006. Sedentary patterns comprise accelerometer-measured average sedentary bout duration and self-reported time of sitting watching TV/videos. Fat distribution (trunk and total fat percentage) was determined via dual X-ray absorptiometry. RESULTS: Among 810 children and 2062 adolescents, average sedentary bout duration was associated with greater total and trunk fat percentages only among male children, after adjusting for moderate-to-vigorous physical activity (MVPA) level by accelerometer. Prolonged sitting watching TV/videos was associated with higher total and trunk fat percentages in male children and all adolescents, independent of levels of MVPA (all P for trend <0.05). Compared with ≤1 h/day, male children who spent ≥4 h/day sitting watching TV/videos had 4.43% higher trunk fat (95% CI, 1.69-7.17%), with similar associations for female (3.53%; 95% CI, 1.03-6.03%) and male adolescents (4.78%; 95% CI, 2.97-6.60%). About 13-17% children and adolescents spent <1 h on MVPA and ≥4 h sitting watching TV/videos per day. Compared with the most active group (MVPA ≥ 1 h/day and sitting watching TV/videos ≤1 h/day), trunk fat in this least active group was 6.21% higher in female children, 9.90% higher in male children, 6.84% higher in female adolescents, and 5.36% higher in male adolescents. CONCLUSIONS: Prolonged time spent on sitting watching TV/videos was associated with fat accumulation among children and adolescents, independent of physical activity level.

Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women.

OBJECTIVE: Sugar-sweetened beverage (SSB) consumption had substantially increased across successive US birth cohorts until 2000, and adolescents and young adults under age 50 years have the highest consumption. However, the link between SSBs and early-onset colorectal cancer (EO-CRC) remains unexamined. DESIGN: In the Nurses' Health Study II (1991-2015), we prospectively investigated the association of SSB intake in adulthood and adolescence with EO-CRC risk among 95 464 women who had reported adulthood beverage intake using validated food frequency questionnaires (FFQs) every 4 years. A subset of 41 272 participants reported beverage intake at age 13-18 years using a validated high school-FFQ in 1998. Cox proportional hazards models were used to estimate relative risks (RRs) with 95% CIs. RESULTS: We documented 109 EO-CRC cases. Compared with individuals who consumed <1 serving/week of SSBs in adulthood, women who consumed ≥2 servings/day had a more than doubled risk of EO-CRC (RR 2.18; 95% CI 1.10 to 4.35; ptrend=0.02), with a 16% higher risk (RR 1.16; 95% CI 1.00 to 1.36) per serving/day increase. Each serving/day increment of SSB intake at age 13-18 years was associated with a 32% higher risk of EO-CRC (RR 1.32; 95% CI 1.00 to 1.75). Replacing each serving/day of adulthood SSB intake with that of artificially sweetened beverages, coffee, reduced fat milk or total milk was associated with a 17%-36% lower risk of EO-CRC. CONCLUSION: Higher SSB intake in adulthood and adolescence was associated with a higher risk of EO-CRC among women. Reduction of SSB consumption among adolescents and young adults may serve as a potential strategy to alleviate the growing burden of EO-CRC.

Characterization of pubertal development of girls in rural Bangladesh.

This study aimed to describe the timing and patterns of pubertal maturation of girls living in rural Bangladesh. Starting in September 2015, a total of 15,320 girls from a birth cohort, aged 9 to 15 years at initial encounter, were visited twice at about a one year interval, typically in their birth month. Participants were asked to self-report extent of pubertal maturation, including breast development, pubic hair growth and age at menarche, if applicable. Pubertal stage (abbreviated as B2 and B3-4 for breast development and PH2 and PH3-4 for pubic hair growth) was assigned. Data from both visits were pooled, yielding a total of 29,377 age-related observations per pubertal characteristic. Probit regression models were used to estimate distributions of age at which each stage of pubertal development was attained. Before age 8, <3% of the study population initiated pubertal maturation as indicated by onset of breast development (B2). The median (95% confidence interval) age of B2 and B3-4 was 11.02 (11.00-11.04) and 12.82 (12.80-12.83) years, respectively; and 12.93 (12.91-12.94) and 14.29 (14.27-14.31) years for the onset (PH2) and advanced stage (PH3-4) of pubic hair growth, respectively. Median age at menarche was 13.17 (13.15-13.19) years, with 2.15 years of timespan from B2 to menarche. Girls in rural Bangladesh progressed through puberty following a well-documented sequence of sexual maturation stages. The age at which each pubertal milestone took place was somewhat later, but the tempo from breast development to menarche was comparable to that observed elsewhere. Our findings present a current norm of pubertal maturation in a typical, rural adolescent population in South Asia, which could help inform future studies and interventions to preserve or improve early adolescent health and development.

Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors.

BACKGROUND & AIMS: Recent increasing trends in early-onset colorectal cancer (CRC) strongly supports that early-life diet is involved in CRC development. However, data are lacking on the relationship with high sugar intake during early life. METHODS: We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses' Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for clustered data. RESULTS: During follow-up, 2909 conventional adenomas (758 high-risk) and 2355 serrated lesions were identified (mean age at diagnoses, 52.2 ± 4.3 years). High sugar and SSB intake during adolescence was positively associated with risk of adenoma, but not serrated lesions. Per each increment of 5% of calories from total fructose intake, multivariable ORs were 1.17 (95% CI, 1.05-1.31) for total and 1.30 (95% CI, 1.06-1.60) for high-risk adenoma. By subsite, ORs were 1.12 (95% CI, 0.96-1.30) for proximal, 1.24 (95% CI, 1.05-1.47) for distal, and 1.43 (95% CI, 1.10-1.86) for rectal adenoma. Per 1 serving/day increment in SSB intake, ORs were 1.11 (95% CI, 1.02-1.20) for total and 1.30 (95% CI, 1.08-1.55) for rectal adenoma. Contrary to adolescent intake, sugar and SSB intake during adulthood was not associated with adenoma risk. CONCLUSIONS: High intake of simple sugars and SSBs during adolescence was associated with increased risk of conventional adenoma, especially rectal adenoma.

Alcohol intake in early adulthood and risk of colorectal cancer: three large prospective cohort studies of men and women in the United States.

Heavy alcohol consumption in mid-adulthood is an established risk factor of colorectal cancer (CRC). Alcohol use in early adulthood is common, but its association with subsequent CRC risk remains largely unknown. We prospectively investigated the association of average alcohol intake in early adulthood (age 18-22) with CRC risk later in life among 191,543 participants of the Nurses' Health Study ([NHS], 1988-2014), NHSII (1989-2015) and Health Professionals Follow-Up Study (1988-2014). Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), which were pooled using random effects models. We documented 2,624 CRC cases. High alcohol consumption in early adulthood (≥ 15 g/day) was associated with a higher CRC risk (multivariable HR 1.28, 95% CI 0.99-1.66, Ptrend = 0.02; Pheterogeneity = 0.44), after adjusting for potential confounding factors in early adulthood. Among never/light smokers in early adulthood, the risk associated with high alcohol consumption in early adulthood was elevated (HR 1.53, 95% CI 1.04-2.24), compared with those who had < 1 g/day of alcohol intake. The suggestive higher CRC risk associated with high alcohol consumption in early adulthood was similar in those who had < 15 g/day (HR 1.35, 95% CI 0.98-1.86) versus ≥ 15 g/day of midlife alcohol intake (HR 1.35, 95% CI 0.89-2.05), compared with nondrinkers in both life stages. The findings from these large prospective cohort studies suggest that higher alcohol intake in early adulthood may be associated with a higher risk of developing CRC later in life.

Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer.

OBJECTIVE: Factors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined. DESIGN: We conducted a nested case-control study among participants aged 18-64 in the IBM MarketScan Commercial Database (2006-2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs. RESULTS: MetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50-64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (ptrend <0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50-64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09). CONCLUSIONS: Metabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.

Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer.

BACKGROUND: The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed younger than age 50 years has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. METHODS: In a prospective cohort study (Nurses' Health Study II), we evaluated 2 empirical dietary patterns (Western and prudent) and 3 recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous or villous histology, high-grade dysplasia, or ≥3 adenomas), among 29 474 women with 1 or more lower endoscopy before age 50 years (1991-2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We documented 1157 early-onset adenomas with 375 at high risk. Western diet was positively associated, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (the highest vs lowest quintile: Western, OR = 1.67, 95% CI = 1.18 to 2.37; prudent, OR = 0.69, 95% CI = 0.48 to 0.98; DASH, OR = 0.65, 95% CI = 0.45 to 0.93; AMED, OR = 0.55, 95% CI = 0.38 to 0.79; AHEI-2010, OR = 0.71, 95% CI = 0.51 to 1.01; all Ptrend ≤ .03), driven by those identified in the distal colon and rectum (all Ptrend ≤ .04, except AMED: Ptrend = .14). CONCLUSION: Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.

Racial differences in prostate cancer: does timing of puberty play a role?

The burden of prostate cancer has a remarkably disproportionate distribution across racial groups. For example, in the USA, African Americans are twice as likely as individuals of European ancestry to develop or die from prostate cancer, and have a more aggressive disease nature at diagnosis. In contrast, Asian American men have the lowest incidence and mortality rates of prostate cancer. That considerable racial disparities exist even in the subclinical stage of prostate cancer among young men in their 20-30s suggests that patterns of prostate carcinogenesis start to diverge even earlier, perhaps during puberty, when the prostate matures at its most rapid rate. Mendelian randomisation studies have provided strong population-based evidence supporting the hypothesis that earlier onset of puberty increases the risk of prostate cancer-particularly of high grade-and prostate cancer-specific mortality later in life, observations which correspond to the epidemiology of the disease in African Americans. Notably, African American boys initiate genital development ~1 year earlier and thus go through longer periods of pubertal maturation compared with European American boys. In this perspective, bringing together existing evidence, we point to puberty as a potential critical window of increased susceptibility to prostate carcinogenesis that could account for the marked prevailing racial differences in the burden of prostate cancer.

Thinness and fecundability: Time to pregnancy after adolescent marriage in rural Bangladesh.

Undernutrition may affect fecundability, but few studies have quantified this relationship. In rural Bangladesh, where newlywed couples face strong pressures to become pregnant, we assessed fecundability, estimated by time to pregnancy (TTP), and its association with preconceptional thinness among nulligravid, newlywed female adolescents. During 2001-2002, 5,516 newlywed women aged 12-19 years participated in a home-based, 5-weekly surveillance system for 5-6 years to enrol pregnant women into an antenatal vitamin A or ß-carotene supplementation trial. Thinness was defined as a left mid-upper arm circumference (MUAC) ≤21.5 versus >21.5 cm. At each visit, staff obtained a monthly history of menstruation. Report of amenorrhea prompted a human chorionic gonadotropin urine test to confirm pregnancy. We derived hazard ratios (with 95% confidence intervals [CI]) for pregnancy and Kaplan-Meier curves for TTP. Ages of women at marriage and pregnancy detection (mean ± standard deviation) were 15.3 ± 1.9 and 17.0 ± 1.9 years, respectively. A total of 82.7% of thinner and 87.3% of better nourished women became pregnant. The unadjusted and multivariable relative hazard of ever becoming pregnant was 0.84 (95% CI [0.78, 0.89]) and 0.86 (95% CI [0.81, 0.92]), respectively, and TTP was 12 weeks longer (median [95% CI]: 63 [58-68] vs. 51 [49-54]) in women whose MUAC was ≤21.5 versus >21.5 cm. In rural Bangladesh, thin adolescent newlywed girls have a lower probability of becoming pregnant and experience a longer time to pregnancy.

Dietary patterns of >30,000 adolescents 9-15 years of age in rural Bangladesh.

Little is known of the usual food intakes of rural adolescents in South Asia. This study describes dietary patterns, based on >91,000 7-day food frequencies among 30,702 girls and boys, aged 9-15 years in rural northwest Bangladesh. Three intake assessments per child, taken across a calendar year, were averaged to represent individual annual intake patterns for 22 food groups. Latent class analysis was used to assign individuals to dietary patterns based on class membership probabilities. The following five dietary patterns (class membership probabilities) were identified: (1) "least diverse" (0.20); (2) "traditional" (0.28); (3) "low vegetable/low fish" (0.23), (4) "moderately high meat" (0.20); and (5) "most diverse" (0.09). The least diverse pattern had the lowest median consumption of most foods and traditional had a relatively higher intake of most vegetables and fish. The most diverse pattern consumed both healthy and processed foods much more often than other patterns. The two most diverse patterns (4 and 5) were associated with higher socioeconomic status, body mass index, height-for-age Z-score, and male gender, and the least diverse pattern showed inverse associations with these characteristics. The most diverse pattern may represent an early wave of the nutrition transition in rural Bangladesh.

Birth weight of Korean infants is affected by the interaction of maternal iron intake and GSTM1 polymorphism.

Excessive iron consumption during pregnancy can lead to increased oxidative stress in the maternal body, which may result in adverse pregnancy outcomes. Glutathione S-transferases (GSTs) originate from a superfamily of detoxifying enzymes that play a role in reducing xenobiotic compounds and oxidative stress. The aim of this study was to determine the relationship among GST gene expression, maternal iron intake during pregnancy, and neonatal birth weight. The study participants were 1087 Korean gravidas and their newborns recruited for the Mothers and Children's Environmental Health study between 2006 and 2010. A 24-h dietary recall interview was conducted to estimate iron intake; additional intake through nutritional supplements was thoroughly investigated. Deletion polymorphisms of GSTM1 and GSTT1 were genotyped using PCR. Dietary iron consumption during pregnancy was positively associated with birth weight in pregnant women who were GSTM1-present after adjustment for the following covariates: maternal age, prepregnancy BMI, mother's education level, log-transformed urinary cotinine level, infant gender, gestational age at term, log-transformed energy intake, parity, and the use of folic acid supplements (P < 0.05). There were interactions between the GSTM1 genotype and iron intakes from animal foods (P < 0.05), diet (P < 0.05), and diet with supplements (P < 0.05). No relationship was found between maternal iron intake and birth weight for the GSTT1 polymorphism. This study demonstrates that increased iron consumption during pregnancy may improve infant birth weight for mothers who are GSTM1-present, but it might not be beneficial for mothers with the GSTM1-null genotype.