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The article focuses on the International Agency for Research on Cancer's (IARC) perspective on alcohol reduction or cessation and its correlation with cancer risk. Topics discussed include the global prevalence of alcohol consumption, the classification of alcoholic beverages and ethanol as human carcinogens, and the estimated number of new cancer cases attributable to alcohol consumption.

Background: Recent studies suggest that untargeted metabolomics is a promising tool to identify novel biomarkers of individual foods. However, few large cross-sectional studies with comprehensive data on habitual diet and circulating metabolites have been conducted.Objective: We aimed to identify potential food biomarkers and evaluate their predictive accuracy.Methods: We conducted a cross-sectional analysis of consumption of 91 food groups or items, assessed by a 152-item food-frequency questionnaire, in relation to 1186 serum metabolites measured by mass spectrometry-based platforms from 1369 nonsmoking postmenopausal women (mean age = 68.3 y). Diet-metabolite associations were selected by Pearson's partial correlation analysis (P < 4.63 × 10-7, |r| > 0.2). The predictive accuracy of the selected food metabolites was evaluated from the area under the curve (AUC) calculated from receiver operating characteristic analysis conducted among women in the top and bottom quintiles of dietary intake.Results: We identified 379 diet-metabolite associations. Forty-two food groups or items were correlated with 199 serum metabolites. We replicated 63 metabolites as biomarkers of habitual food intake reported in previous cross-sectional studies. Among those not previously shown to be associated with habitual diet, several are biologically plausible and were reported in acute feeding studies including: banana and dopamine 3-O-sulfate (r = 0.34, AUC = 76%) and dopamine 4-O-sulfate (r = 0.33, AUC = 74%), garlic and alliin (r = 0.24, AUC = 69%), N-acetylalliin (r = 0.27, AUC = 70%), and S-allylcysteine (r = 0.23, AUC = 69). Two unannotated metabolites were the strongest predictors for dark fish (X-02269, r = 0.51, AUC = 94%) and coffee intake (X-21442, r = 0.62, AUC = 98%).Conclusion: In this comprehensive, cross-sectional analysis of habitual food intake and serum metabolites among postmenopausal women, we identified several potentially novel food biomarkers and replicated others. Our findings contribute to the limited literature on food-based biomarkers and highlight the significant and promising role that large cohort studies with archived blood samples could play in this field. This study was registered at clinicaltrials.gov as NCT03282812. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption is associated with a higher risk of colorectal cancer, but to the authors' knowledge its influence on survival after a diagnosis of colorectal cancer is unclear. The authors investigated associations between prediagnosis and postdiagnosis alcohol intake with mortality among survivors of colorectal cancer.Methods: The authors identified 2458 men and women who were diagnosed with invasive, nonmetastatic colorectal cancer between 1992 (enrollment into the Cancer Prevention Study II Nutrition Cohort) and 2011. Alcohol consumption was self-reported at baseline and updated in 1997, 1999, 2003, and 2007. Postdiagnosis alcohol data were available for 1599 participants.Results: Of the 2458 participants diagnosed with colorectal cancer, 1156 died during follow-up through 2012. Prediagnosis and postdiagnosis alcohol consumption were not found to be associated with all-cause mortality, except for an association between prediagnosis consumption of <2 drinks per day and a slightly lower risk of all-cause mortality (relative risk [RR], 0.86; 95% confidence interval [95% CI], 0.74-1.00) compared with never drinking. Alcohol use was generally not associated with colorectal cancer-specific mortality, although there was some suggestion of increased colorectal cancer-specific mortality with postdiagnosis drinking (RR, 1.27 [95% CI, 0.87-1.86] for current drinking of <2 drinks/day and RR, 1.44 [95% CI, 0.80-2.60] for current drinking of ≥2 drinks/day).Conclusions: The results of the current study do not support an association between alcohol consumption and all-cause mortality among individuals with nonmetastatic colorectal cancer. The association between postdiagnosis drinking and colorectal cancer-specific mortality should be examined in larger studies of individuals diagnosed with nonmetastatic colorectal cancer. Cancer 2017;123:2006-2013. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Dietary energy density (ED) is a measure of diet quality that estimates the amount of energy per unit of food (kilocalories per gram) consumed. Low-ED diets are generally high in fiber and fruits and vegetables and low in fat. Dietary ED has been positively associated with body mass index (BMI) and other risk factors for postmenopausal breast cancer.Objective: We evaluated the associations of total dietary ED and energy-dense (high-ED) foods with postmenopausal breast cancer incidence.Methods: Analyses included 56,795 postmenopausal women from the Cancer Prevention Study II Nutrition Cohort with no previous history of breast or other cancers and who provided information on diet, lifestyle, and medical history in 1999. Multivariable-adjusted breast cancer incidence rate ratios (RRs and 95% CIs) were estimated for quintiles of total dietary ED and for the consumption of high-ED foods in Cox proportional hazards regression models.Results: During a median follow-up of 11.7 y, 2509 invasive breast cancer cases were identified, including 1857 estrogen receptor-positive and 277 estrogen receptor-negative tumors. Median dietary ED was 1.5 kcal/g (IQR: 1.3-1.7 kcal/g). After adjusting for age, race, education, reproductive characteristics, and family history, high compared with low dietary ED was associated with a statistically significantly higher risk of breast cancer (RR for fifth quintile compared with first quintile: 1.20; 95% CI: 1.05, 1.36; P-trend = 0.03). The association between the amount of high-ED foods consumed and breast cancer risk was not statistically significant. We observed no differences by estrogen receptor status or effect modification by BMI, age, or physical activity.Conclusion: These results suggest a modest positive association between total dietary ED and risk of postmenopausal breast cancer. [ABSTRACT FROM AUTHOR]

Background: Results from preclinical studies suggest that flavonoids, which are ubiquitous in plant-based diets, lower breast cancer risk. Epidemiologic studies of flavonoid intake and breast cancer risk, however, are limited, and few investigated associations with the more aggressive estrogen receptor (ER)-negative (ER-) tumors. Objective: We examined the associations between 7 subclasses of dietary flavonoids and invasive postmenopausal breast cancer risk overall and by ER status in a U.S. prospective cohort. Methods: In 1999-2000, 56,630 postmenopausal women completed detailed self-administered questionnaires, among whom 2116 invasive breast cancers were verified during a mean follow-up period of 8.5 y. Cox proportional hazards regression was used to calculate multivariable-adjusted HRs and 95% CIs. Results: Total flavonoid intake was not associated with breast cancer risk. However, there was a modest inverse association between flavone intake and overall breast cancer risk (fifth vs. first quintile HR: 0.88; 95% CI: 0.76, 1.01; P-trend = 0.04) and between flavan-3-ol intake and risk of ER- breast cancer (for an increment of 40 mg/d; HR: 0.81; 95% CI: 0.67, 0.97) but not for ER-positive (ER+) breast cancer risk. Conclusion: The inverse association of flavan-3-ol intake with ER- but not ER+ breast cancer is consistent with other studies that suggest a beneficial role of plant-based diets in ER- breast cancer risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine associations of simple hysterectomy and hysterectomy with bilateral salpingo-oophorectomy (BSO), relative to no surgery, with total and site-specific cancer risk in the Cancer Prevention Study-II Nutrition Cohort. METHODS: We examined associations of hysterectomy with BSO and simple hysterectomy with total and site-specific cancer risk in 66,802 postmenopausal women from the Cancer Prevention Study-II Nutrition Cohort. RESULTS: During a median follow-up of 13.9 years, 8,621 cancers were diagnosed. Hysterectomy with BSO performed at any age (1,892 cases), compared with no hysterectomy (n=5,586 cases), is associated with a 10% reduction in all cancers (relative risk [RR] 0.90, 95% confidence interval [CI] 0.85-0.96). This inverse association does not hold if the surgery occurred at ages 55 years or older (583 cases; RR 1.02, 95% CI 0.94-1.12). Hysterectomy with BSO (715 cases) was associated with a 20% reduction in breast cancer performed at any age (RR 0.80, 95% CI 0.73-0.88). Hysterectomy without BSO was associated with a deceased cancer risk only if performed at age 45 years or younger (541 cases; RR 0.88, 95% CI 0.80-0.97) and overall was associated with a decreased risk of breast cancer (419 cases; RR 0.86, 95% CI 0.76-0.96). CONCLUSION: In a large prospective study, hysterectomy with BSO before age 55 years, relative to no surgery, is associated with a lower risk of total cancer. This information, particularly the lower risk in women younger than 45 years, should be considered in counseling women about ovarian management at the time of surgery. [ABSTRACT FROM AUTHOR]

Background The relationship between active cigarette smoking and breast cancer risk remains controversial because of unresolved issues of confounding and dose response. Methods To investigate these issues further, we analyzed data from 73 388 women in the American Cancer Society's Cancer Prevention Study II (CPS-II) Nutrition Cohort. Analyses were based on 3721 invasive breast cancer case patients identified during a median follow-up of 13.8 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from multivariable-adjusted Cox proportional hazard regression models. P values were two-sided. We also conducted meta-analyses of our results with those published from 14 other cohort studies. Results In CPS-II, incidence was higher in current (HR = 1.24, 95% CI = 1.07 to 1.42) and former smokers (HR = 1.13, 95% CI = 1.06 to 1.21) than in never smokers. Women who initiated smoking before menarche (HR = 1.61,95% CI = 1.10 to 2.34) or after menarche but 11 or more years before first birth (HR = 1.45, 95% CI = 1.21 to 1.74) had higher risk (Ptrend = .03). No relationships were observed with other smoking parameters. Alcohol consumption did not confound associations with smoking status, although neither current nor former smoking were associated with risk among never drinkers (Pinteraction = .11). In meta-analyses, current (HR = 1.12, 95% CI = 1.08 to 1.16) and former smoking (HR = 1.09, 95% CI = 1.04 to 1.15) were weakly associated with risk; a stronger association (HR = 1.21, 95% CI = 1.14 to 1.28) was observed in women who initiated smoking before first birth. Conclusions These results support the hypothesis that active smoking is associated with increased breast cancer risk for women who initiate smoking before first birth and suggest that smoking might play a role in breast cancer initiation. [ABSTRACT FROM AUTHOR]

Although several studies have shown a lower risk of non-Hodgkin lymphoma (NHL) in alcohol drinkers compared with nondrinkers, the dose-response relation and potential differences between former and current drinking and across beverage types and subtypes are unclear. The authors examined associations of alcohol intake with risk of NHL and NHL subtypes in the Cancer Prevention Study II Nutrition Cohort, a prospective study of US men and women aged 50–74 years. Between 1992 and 2007, there were 1,991 incident NHL cases among 143,124 participants. Multivariable-adjusted relative risks and 95% confidence intervals were computed using Cox proportional hazards regression. Compared with nondrinkers, the relative risk of NHL associated with former drinking was 0.90 (95% confidence interval (CI): 0.75, 1.10); the relative risks associated with current intakes of <1, 1–2, and >2 drinks/day were 0.93 (95% CI: 0.83, 1.03), 0.91 (95% CI: 0.78, 1.06), and 0.78 (95% CI: 0.65, 0.93), respectively. Associations did not differ by sex (P-interaction = 0.45) or beverage type (P-difference = 0.22). Alcohol intake was more strongly associated with B-cell lymphoma (P-trend = 0.005) than with T-cell lymphoma (P-trend = 0.76), and associations were similar among B-cell lymphoma subtypes. In this prospective study, current heavy alcohol intake was associated with a reduced risk of NHL. Associations did not differ by beverage type and were slightly stronger for B-cell tumors than for T-cell tumors. [ABSTRACT FROM PUBLISHER]

The article presents the results of a study on the role of alcoholic beverages in the incidence of pancreatic cancer mortality in nonsmokers. According to the authors, nonsmokers who consumed three or more alcoholic beverages per day have 36 percent higher risk of mortality while smokers have 6 percent higher risk. They add that consumption of two or more alcoholic beverages was linked with an increased risk in both smokers and nonsmokers. They indicate the absence of association between beer or wine consumption with pancreatic cancer mortality.

Background: Data are limited on the efficacy of health-focused interventions for young, low-acculturated Latino women. Because breast cancer is the most commonly diagnosed cancer and the most common cause of cancer mortality in this population, combined interventions that address both early detection and dietary patterns could help reduce both morbidity and mortality associated with breast cancer in this underserved population. Purpose: Mujeres Felices por ser Saludables was a randomized intervention study designed to assess the efficacy of an 8-month combined dietary and breast health intervention to reduce fat and increase fiber intake as well as to increase the frequency and proficiency of breast self-examination (BSE) and reduce anxiety related to BSE among Latinas. Methods: Blocked randomization in blocks of 6 was used to randomize 256 20- to 40-year-old Latinas to the intervention(n = 127) or control group (n = 129). The intervention group attended an 8-month multi-component education program designed specifically for low-acculturated Latinas. The control group received mailed health education material on a schedule comparable to the intervention. A total of 195 women (76.2%) completed both the baseline and 8-month follow-up interviews. Results: The intervention and control groups were similar on baseline sociodemographic characteristics. At the 8-month follow up, the intervention group reported lower dietary fat (p < .001) and higher fiber intake (p = .06); a higher proportion reported practicing BSE at the recommended interval (p < .001) and showed improved BSE proficiency (p < .001) compared to the control group. BSE-related anxiety was low for both groups at baseline, and no difference in reduction was observed. Conclusions: This project provides a successful model for achieving dietary change and improving breast health behavior in young, low-acculturated Latinas. [ABSTRACT FROM AUTHOR]

Abstract: To evaluate the associations of changes in diet during adult life with adenoma risk, data from a case-control study of 146 colorectal adenomas and 226 controls were analyzed. Dietary habits during the year before sigmoidoscopy and when subjects were 30 yr old were collected using a food-frequency questionnaire. Change in frequency of consumption during adulthood was calculated by subtracting frequency of consumption of specific foods or food groups at age 30 yr from frequency of consumption during the previous year (recent consumption). Associations with changes in frequency of consumption were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). There was no association for foods or food groups consumed at age 30 yr. For recent consumption, more frequent consumption of red meat, breakfast sausage, and pork chops/ham steaks and less frequent consumption of fish, chicken/turkey, and vegetables were related to a higher risk. Compared with individuals with the highest reduction in consumption since age 30 yr, risks were higher for those with smallest reduction in red meat intake (OR = 2.8; CI = 1.1-7.3), particularly for hamburgers/cheeseburgers (OR = 2.8; CI = 1.2-6.8) and pork chops/ham steaks (OR = 3.7; CI = 1.6-8.7). In contrast, individuals in the highest quartile of increased consumption of fish (OR = 0.6; CI = 0.3-1.1) and vegetables (OR = 0.5; CI = 0.3-1.1) had a lower risk compared with those with minimal increase in consumption. In conclusion, irrespective of frequency of consumption at age 30 yr, a greater reduction in consumption of red meat and a larger increase in consumption of vegetables since age 30 yr were associated with a decreased risk of colorectal adenomas later in life. [ABSTRACT FROM AUTHOR]

: BackgroundBreast cancer is the most commonly diagnosed cancer and the most common cause of cancer mortality among Latino women. Several behavioral factors such as early detection and dietary practices could help decrease morbidity and mortality associated with breast cancer in this population. Unfortunately, there are few data regarding the efficacy of health-related interventions for young Latino women.: MethodsMujeres Felices por ser Saludables is a randomized intervention project designed to assess breast cancer risk reduction behavior among Latino women ages 20–40 years. The primary objectives of the project were to determine whether an 8-month integrated dietary/breast health intervention could lead to a greater reduction in dietary fat, increase in dietary fiber, increase in the frequency and proficiency of breast self examination (BSE), and reduction in anxiety related to BSE compared to controls. Herein we describe the overall design of the project and present baseline characteristics of the 256 randomized women.: ResultsOur results suggest that the average daily intake of dietary fat (percentage of total energy) was slightly below 30% (percentage of total energy) among the women randomized. While over half of these women reported that they practice BSE, and few reported anxiety related to BSE, less than 27% of women were proficient in the recommended BSE technique.: ConclusionsThere are few data on the dietary and breast health behaviors of young low-acculturated Latino women. This study documents the feasibility of recruiting, randomizing, and obtaining both baseline dietary and breast health data on this unique and underserved population. [Copyright &y& Elsevier]

Presents a review of epidemiologic and experimental evidence of human and animal investigations concerning the association of alcohol consumption with increased risk for breast cancer. Methods; Evidence; Alcohol intake and stages of breast carcinogenesis; Interactions of alcohol with other host and environmental factors; Impact of alcohol on hormone status; Experimental evidence; Recommendations.

Context: Previous studies reported an increased risk of pancreatic cancer among persons with diabetes. Few data exist, however, on the association of postload plasma glucose concentration with pancreatic cancer, which could provide insight into the role of abnormal glucose metabolism in the etiology of pancreatic cancer.Objective: To determine the independent association between postload plasma glucose concentration and risk of pancreatic cancer mortality among persons without self-reported diabetes.Design: Prospective cohort study.Setting and Participants: Employees of 84 Chicago-area organizations, with an average age of 40 years at baseline, were screened from 1963 to 1973 and followed up for an average of 25 years. A total of 96 men and 43 women died of pancreatic cancer among 20,475 men and 15,183 women, respectively.Main Outcome Measures: Relationship of pancreatic cancer mortality with postload plasma glucose levels.Results: Compared with a postload plasma glucose level of 6.6 mmol/L (119 mg/dL) or less and after adjusting for age, race, cigarette smoking, and body mass index, the relative risks (95% confidence intervals) of pancreatic cancer mortality were 1.65 (1.05-2.60) for postload plasma glucose levels between 6.7 (120) and 8.8 (159) mmol/L (mg/dL); 1.60 (0.95-2.70) for levels between 8.9 (160) and 11.0 (199); and 2.15 (1.22-3.80) for levels of 11.1 (200) or more; P for trend=.01. An association appeared to be stronger for men than women. Estimates were only slightly lower after excluding 11 men and 2 women who died of pancreatic cancer during the first 5 years of follow-up. In men only, higher body mass index and serum uric acid concentration also were independently associated with an elevated risk of pancreatic cancer mortality.Conclusion: These results suggest that factors associated with abnormal glucose metabolism may play an important role in the etiology of pancreatic cancer. JAMA. 2000;283:2552-2558 [ABSTRACT FROM AUTHOR]

Presents a study to determine the association between hormone replacement therapy (HRT) in menopause and breast cancer. Risk of ductal carcinoma in situ (DCIS), invasive carcinoma with favorable histology, and invasive ductal or lobular carcinoma; Context; Design; Results; Conclusion.

Chromatographic, peptide mapping and mass spectrometric analysis were used to examine hemoglobin (Hb) from heavy drinkers and abstainers for alcohol consumption-related modifications. Heavy drinker and abstainer hemoglobin samples contained similar amounts of glycosylated Hb and significantly different (p < 0.05) amounts of 'fast' hemoglobin. The presence of higher amounts of 'fast' Hb in heavy drinker relative to abstainer samples suggested the presence of alcohol-consumption related modifications. To further examine Hb for modifications, tryptic peptides of the 'fast' hemoglobin HbA1c were isolated and analyzed by plasma desorption mass spectrometry (PDMS). [14Clacetaldehyde (AcH)-Hb was synthesized in vivo for use as standard. Specific peptides were chosen based on co-migration with radiolabeled peptides from tryptic digest of the [14C]acetaldehyde-Hb. The masses obtained by PDMS for two heavy drinker peptides were identical to two radiolabeled peptides; the two pairs of peptides co-migrated on HPLC. A comparison of the observed mass for the peptides with the theoretical masses for acetaldehyde-modified Hb peptides suggested that the peptides were AcH-modified alpha and beta chain N-termini of Hb. The modified peptides were found in five of six heavy drinker samples. This is the first description of site-specific AcH-Hb adducts occurring in vivo. The routine detection of such adducts has potential for characterizing usual alcohol intake. [ABSTRACT FROM AUTHOR]

Background: The relationship between time-use behaviors and prospective weight change is poorly understood. Methods: A subset of Cancer Prevention Study-3 participants (n = 549, 58% women, 66% non-Latinx white) self-reported weight in 2015 and 2018 and completed an accelerometer protocol for seven days. Sedentary time, sleep, light, moderate, and vigorous intensity physical activity (PA) were treated as a compositional variable and multiple linear regression was used to examine associations between activity composition and weight change stratified by sex and race/ethnicity. Compositional isotemporal substitution analysis was used to quantify change in weight associated with reallocating 30 min./day. Results: Activity composition was associated with weight change among women (p = 0.007), but not men (p = 0.356), and among Latinx (p = 0.032) and white participants (p = 0.001), but not Black participants (p = 0.903). Replacement of 30 min./day sedentary time with moderate-vigorous PA was associated with 3.49 lbs. loss (-6.76, -0.22) in Latinx participants and replacement with sleep was associated with 1.52 (0.25, 2.79) and 1.31 (0.40, 2.21) lbs. gain in white women and men. Conclusion: The distribution of time spent in daily behaviors was associated with three-year weight change in women, Latinx, and white participants. This was the first longitudinal compositional study of weight change; thus, more studies are needed. [ABSTRACT FROM AUTHOR]

Background: Studies show that regular moderate to vigorous physical activity is associated with a lower risk of cardiovascular disease, certain cancers, and premature death, but few studies have examined associations of light-intensity physical activity (LPA) and mortality, especially among older adults.Objectives: The aim of this study was to investigate the association of LPA with the risks of death from all causes, cancer, cardiovascular diseases, and respiratory diseases among older adults in the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC).Methods: Analyses included 123,232 participants in CPS-II NC, among whom 46,829 died during follow-up (1993-2014). Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for self-reported leisure time LPA associated with mortality.Results: Engaging in little or no LPA (<3 metabolic equivalent [MET]-h/week) was associated with a 16% higher risk of all-cause mortality (HR 1.16, 95% CI 1.12-1.20) compared to engaging in some LPA (3 to <9 MET-h/week) after adjusting for moderate to vigorous physical activity. However, there was no evidence of a dose-response relationship. A statistically significant interaction with age suggested that more LPA was associated with a lower risk of respiratory disease mortality only among participants aged ≥70 years (21+ vs. 3 to <9 MET-h/week, HR 0.78, 95% CI 0.66-0.91; pint = 0.003).Conclusions: In this prospective study of older adults, accumulating little/no leisure time LPA was associated with a higher risk of mortality. It is of substantial public health value to demonstrate the potential benefits of engaging in any activity, even if light in intensity, among older adults given the aging US population. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of sleep difficulties in a large cohort of long-term cancer survivors (>5 years) and examine associations with four domains of cancer-related problems.Methods: This study analyzed a nationwide sample (N = 1903) of cancer survivors (31% Breast; 20% prostate) at nine years (m = 8.9 sd = 0.6) post-diagnosis with a mean age of 64.5 years. Sleep quality and sleep disturbance were assessed by the Pittsburgh Sleep Quality Index. Multivariable logistic regression models examined associations between cancer-related problems (physical distress, emotional distress, economic distress, and fear of recurrence) and sleep difficulty (poor vs. low sleep quality and high vs. low sleep disturbance). Odds ratios (OR) and 95% confidence intervals (CI) were estimated, adjusting for medico-demographics, behavioral factors, and sleep medication use.Results: In sum, 20% percent of the sample reported poor sleep quality, 51% reported high sleep disturbance and 17% reported both. Sleep medication use was reported by 28% of the total sample. All four domains of cancer-related problems were significantly associated with poor sleep quality and high sleep disturbance. Above median cancer-related physical distress had the strongest association with both poor sleep quality (OR = 3.42; 95% CI = 2.44-4.79) and high sleep disturbance (OR = 4.06; 95% CI = 3.09-5.34).Conclusions: Among nine-year cancer survivors, multiple domains of cancer-related health problems were associated with sleep difficulties. Knowledge of the relationship between cancer-related problems and sleep may aid clinicians during the evaluation and treatment of sleep problems in long-term cancer survivors. Future research should utilize prospective data to better understand the causal nature of the associations. [ABSTRACT FROM AUTHOR]

The authors reflect on the progress of efforts to find a cure for cancer in the U.S. They note the human and economic costs of cancer. They also cite the factors that make the progress in the fight against cancer complicated, including demographic trends, susceptibility to treatment and multiple molecular variants of cancer with different prognosis. They state that the reduction of cigarette smoking in the U.S. is one of the biggest successes to date in the primary prevention of cancer and other chronic diseases during the last 50 years.

This article presents an editorial commenting on a study in this issue about the role of a healthy diet in breast cancer survivors which showed no benefit from the healthy diet on cancer recurrence. A similar study had dissimilar results finding just the opposite. The authors discuss the differences in the two studies and say that until there is more data, dietary recommendations to improve long-term prognosis in early stage breast cancer survivors is not supported.

Editorial. Offers observations on the prevention of pancreatic cancer. Reference to an article in this issue by Michaud et al about the link between pancreatic cancer and height, obesity and physical activity; Findings which support a hypothesis that hyperinsulinemia could play an important role in pancreatic carcinogenesis; Conclusion that pancreatic cancer could be prevented though lifestyle and behavioral changes.

Introduction: Secondhand smoke is known to have adverse effects on the lung and vascular systems in both children and adults. It is unknown if childhood exposure to secondhand smoke is associated with adult mortality.Methods: The authors examined associations of childhood and adult secondhand smoke exposure with death from all causes, ischemic heart disease, stroke, and chronic obstructive pulmonary disease among 70,900 never smoking men and women, predominantly aged ≥50 years, from the Cancer Prevention Study-II Nutrition Cohort in 1992-1993. There were 25,899 participant deaths during follow-up through 2014. During 2016-2017, Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios and 95% CIs.Results: Childhood secondhand smoke exposure was not associated with all-cause mortality. However, childhood secondhand smoke (living with a smoker for 16-18 years during childhood) was associated with higher mortality from chronic obstructive pulmonary disease (hazard ratio=1.31, 95% CI=1.05, 1.65). Adult secondhand smoke exposure of ≥10 hours/week at enrollment was associated with a higher risk of all-cause (hazard ratio=1.09, 95% CI=1.04, 1.14); ischemic heart disease (hazard ratio=1.27, 95% CI=1.14, 1.42); stroke (hazard ratio=1.23, 95% CI=1.04, 1.45); and chronic obstructive pulmonary disease (hazard ratio=1.42, 95% CI=0.97, 2.09) mortality.Conclusions: These results suggest that childhood secondhand smoke exposure, as well as adult secondhand smoke exposure, increase the risk of chronic obstructive pulmonary disease death in adulthood. Consistent with previous studies, the results also show that adult secondhand smoke is meaningfully associated with higher mortality from vascular disease and all causes. Overall, these findings provide further evidence for reducing secondhand smoke exposure throughout life. [ABSTRACT FROM AUTHOR]

Background Large prospective cohort studies need to confirm the associations between recreational physical activity (PA), including the most common type—walking, and prostate cancer–specific mortality (PCSM) among prostate cancer patients. Objective To investigate the associations of recreational PA, reported before and after diagnosis, with PCSM, overall and by tumor risk category. Design, setting, and participants In a prospective cohort study conducted in the USA, men diagnosed with nonmetastatic prostate cancer between 1992/1993 and June 2011 were followed for mortality until 2012. Patients were included in pre- ( n = 7328) and/or postdiagnosis ( n = 5319) analyses. Outcome measurements and statistical analysis Cox proportional hazards models were used to assess PCSM with recreational PA. Results and limitations A total of 454 and 261 prostate cancer deaths occurred during pre- and postdiagnosis follow-up, respectively. Prior to diagnosis, engaging in ≥17.5 metabolic equivalent hours per week (MET-h/wk) of recreational PA, compared with 3.5–<8.75 MET-h/wk, was associated with a significant 37% lower risk of PCSM (hazard ratio: 0.63, 95% confidence interval: 0.43–0.91, p trend = 0.03) only among men with lower-risk tumors (Gleason score 2–7 and T1–T2; p interaction = 0.02). A similar result was seen for walking but not for other recreational PA. After diagnosis, the same comparison (≥17.5 vs 3.5–<8.75 MET-h/wk) was associated with a significant 31% lower risk of overall PCSM (hazard ratio: 0.69, 95% confidence interval: 0.49–0.95, p trend = 0.006), which did not differ by tumor risk category. Postdiagnosis walking had a suggestive inverse association with PCSM ( p trend = 0.07). These results were observational and may not be generalized to patients with metastatic prostate cancer. Residual confounding due to a higher screening rate among men with lower-risk tumors cannot be ruled out. Conclusions The findings provide additional evidence for prostate cancer survivors to adhere to PA recommendations, and support clinical trials of exercise among prostate cancer survivors with progression or mortality as outcomes. Patient summary In a large follow-up study of men diagnosed with nonmetastatic prostate cancer, those who exercise more after diagnosis had a lower risk of dying from prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Studies of breast cancer in women and laboratory studies provide evidence that shift work involving circadian rhythm disruption is a probable human carcinogen. However, evidence linking shift work and other circadian disruption factors to prostate cancer risk is limited. Purpose: To examine associations of work schedule (i.e., rotating shift work, fixed night and fixed afternoon/evening shift work); sleep duration; and insomnia frequency with prostate cancer mortality. Methods: The Cancer Prevention Study–II is a large prospective cohort study of U.S. adults. Work schedule, sleep duration, insomnia frequency, and other information was self-reported in 1982. Among 305,057 employed men, aged ≥29 years who were cancer free at baseline, there were 4974 prostate cancer deaths during follow-up through 2010. In 2013, multivariable-adjusted relative risks (RRs) and 95% CIs were computed using Cox proportional hazards regression. Results: Work schedule and insomnia frequency were not associated with risk of fatal prostate cancer. Short sleep duration was associated with higher risk of prostate cancer during the first 8 years of follow-up, compared to 7 hours/night, the RRs (95% CIs) for 3–5 and 6 hours/night were 1.64 (1.06, 2.54), and 1.28 (0.98, 1.67), respectively. There was no association between sleep duration and fatal prostate cancer during later follow-up. Conclusions: These results do not support associations of work schedule or insomnia frequency with prostate cancer mortality. The association between short sleep duration and higher risk of fatal prostate cancer only during the first 8 years of follow-up suggests that short sleep duration could affect later stages of prostate carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have sought to identify genes that influence the ability to quit smoking, but none found any that are consistently associated with smoking cessation.Methods: We developed a novel difficulty of quitting smoking phenotype based on the extremes of the number of quit attempts needed to achieve successful abstinence: Easy quitters were defined as having achieved long-term (>1 year) abstinence after their first quit attempt and difficult quitters as having reported 10 or more quit attempts. We conducted a two-stage study to determine if this phenotype could be useful for identifying single nucleotide polymorphisms (SNPs) that influence smoking cessation. In stage 1, 82 SNPs in 26 genes involved in nicotine signaling and metabolism were genotyped in 1357 easy quitters and 1321 difficult quitters from Cancer Prevention Study 3 (CPS-3). In stage 2, the 11 SNPs associated with difficult quitting in stage 1 (p < .1) were genotyped in an independent sample of 1300 easy quitters and 1299 difficult quitters from CPS-3.Results: Three of 11 SNPs (HTR1B rs6298, NR4A2 rs834829, and CYP2A65 rs8192729) were significantly associated with the difficult quitting phenotype in stage 2 (p < .05). In addition, a polygenic risk score based on the 11 SNPs identified in stage 1 was significantly associated with the difficult quitting phenotype in stage 2 (odds ratio = 1.08, 95% confidence interval: 1.03-1.14 per quintile, p trend = 4.5×10-3).Conclusions: Using a novel difficulty of quitting phenotype, three gene variants and a polygenic risk score based on 11 SNPs were found to be significantly associated with smoking cessation.Implications: Our results provide evidence that a difficulty of quitting smoking phenotype based on the extremes of number of quit attempts could be a useful tool for identifying genetic variants that influence difficulty of smoking cessation. Knowledge of these genetic variants will indicate biological pathways that could be targeted for the development of novel smoking cessation aids and could be used to determine which smokers are most likely to benefit from such smoking cessation aids. [ABSTRACT FROM AUTHOR]

Background Study results on overall seroprevalence of Helicobacter pylori and colorectal cancer risk have been inconsistent. However, one study found positive associations with antibodies to specific H. pylori proteins. To follow up on those findings, we assessed associations of 15 H. pylori specific proteins with colorectal cancer incidence in the prospective Cancer Prevention Study- II Nutrition Cohort. Materials and Methods Participants in this nested case-control study included 392 cases and 774 controls who were predominantly elderly (median age at blood draw: 71 years) and Caucasian (98%). Seroreactivity against 15 H. pylori proteins was assessed by fluorescent bead-based multiplex serology and associations with colorectal cancer were estimated using conditional logistic regression. Results Helicobacter pylori serostatus was not associated with colorectal cancer incidence (odds ratio ( OR), 1.17, 95% confidence interval (95% CI), 0.91-1.50). Among individual antigens, GroEl serostatus was associated with colorectal cancer risk ( OR, 1.32, 95% CI: 1.03-1.70), whereas CagM was associated with colon cancer risk only ( OR, 1.35, 95% CI: 1.01-1.80). No dose-response relationships were observed for any of the antigens, including GroEl and CagM. Conclusions The results of our study do not support an association between H. pylori infection and colorectal cancer risk in this elderly, mostly Caucasian population. [ABSTRACT FROM AUTHOR]

Remaining controversies on the association between body mass index (BMI) and mortality include the effects of smoking and prevalent disease on the association, whether overweight is associated with higher mortality rates, differences in associations by race and the optimal age at which BMI predicts mortality. To assess the relative risk (RR) of mortality by BMI in Whites and Blacks among subgroups defined by smoking, prevalent disease, and age, 891,572 White and 38,119 Black men and women provided height, weight and other information when enrolled in the Cancer Prevention Study II in 1982. Over 28 years of follow-up, there were 434,400 deaths in Whites and 18,702 deaths in Blacks. Cox proportional-hazards regression was used to estimate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI). Smoking and prevalent disease status significantly modified the BMI-mortality relationship in Whites and Blacks; higher BMI was most strongly associated with higher risk of mortality among never smokers without prevalent disease. All levels of overweight and obesity were associated with a statistically significantly higher risk of mortality compared to the reference category (BMI 22.5–24.9 kg/m2), except among Black women where risk was elevated but not statistically significant in the lower end of overweight. Although absolute mortality rates were higher in Blacks than Whites within each BMI category, relative risks (RRs) were similar between race groups for both men and women (p-heterogeneity by race  = 0.20 for men and 0.23 for women). BMI was most strongly associated with mortality when reported before age 70 years. Results from this study demonstrate for the first time that the BMI-mortality relationship differs for men and women who smoke or have prevalent disease compared to healthy never-smokers. These findings further support recommendations for maintaining a BMI between 20–25 kg/m2 for optimal health and longevity. [ABSTRACT FROM AUTHOR]

Background A recent pooled analysis of randomized trials of daily aspirin for prevention of vascular events found a substantial reduction (relative risk [RR] = 0.63, 95% confidence interval [CI] = 0.49 to 0.82) in overall cancer mortality during follow-up occurring after 5 years on aspirin. However, the magnitude of the effect of daily aspirin use, particularly long-term use, on cancer mortality is uncertain. Methods We examined the association between daily aspirin use and overall cancer mortality among 100 139 men and women with no history of cancer in the Cancer Prevention Study II Nutrition Cohort. Cox proportional hazards regression models were used to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs). Results Between 1997 and 2008, 5138 participants died from cancer. Compared with no use, daily aspirin use at base-line was associated with slightly lower cancer mortality, regardless of duration of daily use (for <5 years of use, RR = 0.92, 95% CI = 0.85 to 1.01; for >5 years of use, RR = 0.92, 95% CI = 0.83 to 1.02). Associations were slightly stronger in analyses that used updated aspirin information from periodic follow-up questionnaires and included 3373 cancer deaths (for <5 years of use, RR = 0.84, 95% CI = 0.76 to 0.94; for >5 years of use, RR = 0.84, 95% CI = 0.75 to 0.95). Conclusion These results are consistent with an association between recent daily aspirin use and modestly lower cancer mortality but suggest that any reduction in cancer mortality may be smaller than that observed with long-term aspirin use in the pooled trial analysis. [ABSTRACT FROM AUTHOR]

Background A recent pooled analysis of randomized trials of daily aspirin for prevention of vascular events found a substantial reduction (relative risk [RR] = 0.63, 95% confidence interval [CI] = 0.49 to 0.82) in overall cancer mortality during follow-up occurring after 5 years on aspirin. However, the magnitude of the effect of daily aspirin use, particularly long-term use, on cancer mortality is uncertain. Methods We examined the association between daily aspirin use and overall cancer mortality among 100 139 men and women with no history of cancer in the Cancer Prevention Study II Nutrition Cohort. Cox proportional hazards regression models were used to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs). Results Between 1997 and 2008, 5138 participants died from cancer. Compared with no use, daily aspirin use at baseline was associated with slightly lower cancer mortality, regardless of duration of daily use (for <5 years of use, RR = 0.92, 95% CI = 0.85 to 1.01; for ≥5 years of use, RR = 0.92, 95% CI = 0.83 to 1.02). Associations were slightly stronger in analyses that used updated aspirin information from periodic follow-up questionnaires and included 3373 cancer deaths (for <5 years of use, RR = 0.84, 95% CI = 0.76 to 0.94; for ≥5 years of use, RR = 0.84, 95% CI = 0.75 to 0.95). Conclusion These results are consistent with an association between recent daily aspirin use and modestly lower cancer mortality but suggest that any reduction in cancer mortality may be smaller than that observed with long-term aspirin use in the pooled trial analysis. [ABSTRACT FROM PUBLISHER]

Background: The inactivity physiology paradigm proposes that sedentary behaviors, including sitting too much, are independent of the type of physical activity delineated for health in the Physical Activity Guidelines for Americans. Thus, we hypothesized that, when accounting for behaviors across the entire day, variability in the amount of time spent sitting would be independent of the inter-and intra-individual time engaged in sustained moderate-to-vigorous physical activity (MVPA). Methods: Ninety-one healthy women, aged 40-75 years, completed a demographic questionnaire and assessment of height and weight. Participants wore the activPAL activity monitor for one week and time (minutes/day) spent sitting, standing, stepping, and in sustained bouts (bouts ?10 minutes) of MVPA were quantified. The women were then stratified into groups based on weekly sustained MVPA. Additionally, each day of data collection for each participant was classified as either a "sufficient" MVPA day (? 30 min of MVPA) or an "insufficient" MVPA day for within-participant analyses. Results: Time spent sitting, standing, and in incidental non-exercise stepping averaged 64, 28, and 11 hrs/week, respectively, and did not differ between groups with individuals meeting/exceeding the current exercise recommendation of 150 min/week of sustained MVPA in ≥10 minutes bouts (M = 294 min/week, SD = 22) compared to those with none or minimal levels (M= 20min/week, SD = 4). Time spent sitting (M = 9.1 hr/day, SD = 0.19 vs. M = 8.8 hr/day, SD = 0.22), standing (M = 3.9 hr/day, SD = 0.16 vs. M = 3.9 hr/day, SD = 0.15), and in intermittent stepping (M = 1.6 hr/day, SD = 0.07 vs. M = 1.6 hr/day, SD = 0.06) did not differ between days with (~55 min/day) and without recommended MVPA. Conclusions: This study provides the first objective evidence that participation in sustained MVPA is unrelated to daily sitting duration in relatively healthy, middle and older-aged women. More research is needed to extend these findings to other populations and to inform distinct behavioral recommendations focused on sedentary time. [ABSTRACT FROM AUTHOR]

Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (Ptrend = 0.68) or by sex (men, Ptrend = 0.50; women, Ptrend = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight–NHL association should consider alternative mechanisms, such as immunologic effects. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Conflicting findings exist regarding the associations of sex hormones with subclinical atherosclerosis. Methods: This is a substudy from MESA of 881 postmenopausal women and 978 men who had both abdominal aortic calcification (AAC) quantified by computed tomography and sex hormone levels assessed [Testosterone (T), estradiol (E2), dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG)]. We examined the association of sex hormones with presence and extent of AAC. Results: For women, SHBG was inversely associated with both AAC presence [OR=0.62, 95% CI 0.42–0.91 for 1 unit greater log(SHBG) level] and extent [0.29 lower log(AAC) for 1 unit greater log(SHBG) level, β =−0.29 (95% CI −0.57 to −0.006)] adjusting for age, race, hypertension, smoking, diabetes, BMI, physical activity, and other sex hormones. After further adjustment for total and HDL-cholesterol, SHBG was not associated with ACC presence or extent. In men, there was no association between SHBG and AAC. In both men and women, neither T, E2, nor DHEA was associated with AAC presence or extent. Conclusion: After adjustment for non-lipid cardiovascular risk factors, SHBG levels are inversely associated with both the presence and severity of AAC in women but not in men, which may be accounted for by HDL. [Copyright &y& Elsevier]

Abstract: To investigate the association between sun exposure and risk of non-Hodgkin lymphoma (NHL) by histologic subtypes and to explore whether or not vitamin D intake modify sun–NHL association, we analysed data from a population-based, case–control study conducted in Nebraska between 1999 and 2002. Information on sun exposure during the spring, summer, fall and winter was collected from 387 cases and 535 controls by telephone interview. We found no association between seasonal sun exposure and risk of NHL. Vitamin D intake was also not associated with NHL risk, nor does it modify the sun–NHL association. In contrast, total hours of sun exposure was inversely associated with the risk of NHL (odds ratio (OR)=0.7 comparing >30h/week to <14h/week, 95% confidence interval (CI)=0.5–1.1). Sun exposure was associated with a lower risk of NHL among farmers (OR=0.8, 0.5–1.3 for 14–30h/week; OR=0.6, 0.3–0.9 for >30h/week; p-trend=0.02), but not among non-farmers. Total hours of sun exposure was also inversely associated with risk of diffuse large B-cell lymphoma and T-cell lymphoma. In conclusion, our data suggest that total hours of sun exposure is associated with a lower risk of NHL, and the inverse association is not modified by vitamin D intake, is stronger among farmer, and may vary by subtypes. [Copyright &y& Elsevier]

Method. Two hundred fifty-six 20-40 year-old Latinas were randomly assigned to the intervention (n=127) or control group (n=129). Data were collected at a baseline and eight-months after randomization. Results. Compared to women who attended 0-2 sessions, those who attended at least three of the 16 sessions reported lower dietary fat (p<.001) and improved BSE proficiency (p<.001). However, there were no differences in fiber intake at eight months. Women who attended at least three sessions were more likely to be lower in acculturation. Conclusions. The optimal length for health-risk reduction interventions is unknown. Our results suggest that, while participation is associated with improved outcomes, fewer sessions than traditionally offered in most behavioral interventions may be sufficient to effect initial behavior change. [ABSTRACT FROM AUTHOR]

Several chemicals have been associated with risk of non-Hodgkin's lymphoma (NHL), many of which are substrates for N-acetyltransferase (NAT) and glutathione S-transferase (GST) enzymes. We investigated the association between polymorphisms in genes coding for these enzymes and NHL risk in a population-based study (389 cases and 535 controls).NAT1slow genotype was associated with a slightly increased risk in women [odds ratios (OR) = 1·4; 95% confidence interval (CI) = 0·9–2·3], but not in men.NAT2slow genotype was not associated with risk in either sex. The two slow genotypes ofNAT1andNAT2combined were associated with a minor increase of risk in women (OR = 1·4; 0·8–2·4). There was no association with theGSTM1orGSTT1null genotype in either sex, irrespective of histological subtypes. Individuals withGSTP1 Valhomozygotes had non-significant excessive risk of marginal zone lymphoma (OR = 1·8; 0·6–5·1) and‘other’ B-cell NHLs (OR = 1·6; 0·7–3·6), but lower risk of diffuse large B-cell lymphoma (OR = 0·2; 0·1–0·96). Risk did not elevate with an increasing number of high-riskGSTalleles in either sex. In summary, althoughNAT1,NAT2,GSTM1,GSTT1, orGSTP1polymorphisms do not appear to be associated with NHL risk overall, there might be gender-specific and subtype-specific associations that require confirmation. [ABSTRACT FROM AUTHOR]

Background: There is an urgent need to identify factors specifically associated with aggressive prostate cancer (PCa) risk. We investigated whether rare pathogenic, likely pathogenic, or deleterious (P/LP/D) germline variants in DNA repair genes are associated with aggressive PCa risk in a case-case study of aggressive vs nonaggressive disease.Methods: Participants were 5545 European-ancestry men, including 2775 nonaggressive and 2770 aggressive PCa cases, which included 467 metastatic cases (16.9%). Samples were assembled from 12 international studies and germline sequenced together. Rare (minor allele frequency < 0.01) P/LP/D variants were analyzed for 155 DNA repair genes. We compared single variant, gene-based, and DNA repair pathway-based burdens by disease aggressiveness. All statistical tests are 2-sided.Results: BRCA2 and PALB2 had the most statistically significant gene-based associations, with 2.5% of aggressive and 0.8% of nonaggressive cases carrying P/LP/D BRCA2 alleles (odds ratio [OR] = 3.19, 95% confidence interval [CI] = 1.94 to 5.25, P = 8.58 × 10-7) and 0.65% of aggressive and 0.11% of nonaggressive cases carrying P/LP/D PALB2 alleles (OR = 6.31, 95% CI = 1.83 to 21.68, P = 4.79 × 10-4). ATM had a nominal association, with 1.6% of aggressive and 0.8% of nonaggressive cases carrying P/LP/D ATM alleles (OR = 1.88, 95% CI = 1.10 to 3.22, P = .02). In aggregate, P/LP/D alleles within 24 literature-curated candidate PCa DNA repair genes were more common in aggressive than nonaggressive cases (carrier frequencies = 14.2% vs 10.6%, respectively; P = 5.56 × 10-5). However, this difference was non-statistically significant (P = .18) on excluding BRCA2, PALB2, and ATM. Among these 24 genes, P/LP/D carriers had a 1.06-year younger diagnosis age (95% CI = -1.65 to 0.48, P = 3.71 × 10-4).Conclusions: Risk conveyed by DNA repair genes is largely driven by rare P/LP/D alleles within BRCA2, PALB2, and ATM. These findings support the importance of these genes in both screening and disease management considerations. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, few studies to date have examined associations between moderate to vigorous physical activity (MVPA) and sitting time with quality of life in cancer survivors compared with a cancer‐free group. The current study examined differences in global mental health (GMH) and global physical health (GPH) across levels of MVPA and sitting among cancer survivors and cancer‐free participants. Methods: Cancer Prevention Study II participants (59.9% of whom were female with an age of 77.8 ± 5.8 years) were grouped as: 1) survivors who were 1 to 5 years after diagnosis (3718 participants); 2) survivors who were 6 to 10 years after diagnosis (4248 participants); and 3) cancer‐free participants (ie, no history of cancer; 69,860 participants). In 2009, participants completed MVPA, sitting, and Patient‐Reported Outcomes Measurement Information System GMH/GPH surveys. Mean differences in GMH and GPH T scores across MVPA (none, 0 to <7.5, 7.5 to <15, 15 to <22.5, and ≥22.5 metabolic equivalent [MET]‐hours/week) and sitting (0 to <3, 3 to <6, and ≥6 hours/day) were assessed using multivariate generalized linear models. Results: The mean GMH and GPH scores were statistically significantly higher in cancer‐free participants compared with cancer survivor groups, although the differences were not clinically meaningful (mean difference of 0.52 for GMH and 0.88 for GPH). More MVPA was associated with higher GMH and GPH scores for all 3 groups (P for trend <.001), and differences between the least and most active participants were found to be clinically meaningful (mean differences of ≥4.34 for GMH and ≥6.39 for GPH). Similarly, a lower duration of sitting was associated with higher GMH and GPH scores for all groups (P for trend <.001), with clinically meaningful differences observed between the least and most sedentary participants (mean differences of ≥2.74 for GMH and ≥3.75 for GPH). Conclusions: The findings of the current study provide evidence of the importance of increased MVPA and decreased sitting for improved health in older adults with or without a prior cancer diagnosis. More physical activity appears to be associated with higher global mental and physical health for short‐term and long‐term cancer survivors, and differences between the least and most active individuals are found to be clinically meaningful. Similarly, a lower duration of sitting is associated with higher global mental and physical health for short‐term and long‐term cancer survivors, with clinically meaningful differences noted between those who are the least and most sedentary. [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk.Methods: We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided.Results: Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes.Conclusion: These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25–2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06–1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04–1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09–1.31) and EHBDC (HR 1.11; 95% CI 1.01–1.22) in Asian women only. We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers. • We pooled data from 19 longitudinal studies to estimate the associations between female reproductive factors and BTC. • The risk of GBC was increased with increasing number of live births in all women. • The risk of GBC, IHBDC, and EHBDC were increased with later age of menarche among women from Asian countries only. • Age of menopause was not associated with an increased risk of any BTC. [ABSTRACT FROM AUTHOR]

Background: Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk.Methods: Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up.Results: Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2-4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5-<9 kg lost: HR = 0.75, 95% CI = 0.63 to 0.90; ≥9 kg lost: HR = 0.68, 95% CI = 0.50 to 0.93). Women who lost at least 9 kg and gained back some (but not all) of it were also at a lower risk of breast cancer. Other patterns of weight loss and gain over the two intervals had a similar risk of breast cancer to women with stable weight.Conclusions: These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese. [ABSTRACT FROM AUTHOR]

Purpose: Evidence supports a role of whole grains in colorectal cancer (CRC) prevention, but the association between gluten intake and CRC risk in healthy populations is unclear. We examined the association of grain and gluten intake with risk of CRC overall and by subsite among Cancer Prevention Study-II Nutrition Cohort participants. Methods: In 1999, 50,118 men and 62,031 women completed food frequency questionnaires assessing grain intake. Gluten intake was estimated using the protein content of grain products. Multivariable-adjusted hazards ratio (HR) and 95% confidence interval (CI) of CRC risk were estimated using Cox proportional hazards regression. Results: During follow-up through 2013, 1742 verified CRC cases occurred. For the highest vs. lowest quintiles of whole grain intake, HRs (95% CIs) of CRC risk were 0.77 (0.61–0.97; P trend = 0.03) among men and 1.10 (95% CI 0.88–1.36; P trend = 0.14) among women (P interaction by sex = 0.01). Men in the highest vs. lowest quintile of whole grain intake had a 43% lower risk of rectal cancer (HR = 0.57, 95% CI 0.35–0.93, P trend = 0.04). Gluten intake was not associated with CRC risk overall (HR = 1.10, 95% CI 0.93–1.32, P trend = 0.10), but was associated with risk of proximal colon cancer among men and women, combined (HR = 1.37, 95% CI 1.07–1.75, quintile 5 vs. 1, P trend = 0.001) and separately. Refined grains and grain-based sweets were not associated with CRC risk. Conclusions: We found that higher whole grain intake was associated with lower CRC risk among older US men, but not women. The positive association of gluten intake with the risk of proximal colon cancer deserves further study. [ABSTRACT FROM AUTHOR]

Background: Height and weight are commonly used metrics in epidemiologic studies to calculate body mass index. Large cohort studies generally assess height and weight by self-report rather than by measurement. The aim of this study was to assess the validity of self-reported height and weight in the Cancer Prevention Study-3 (CPS-3), a large, nationwide cohort recruited by the American Cancer Society between 2006–2013. Methods: In a subset of CPS-3 participants (n = 2,643), weight and height were assessed at the same time via self-report and in-person measurement. BMI was calculated and classified underweight (<18.5 kg/m2), normal (18.5-<25 kg/m2), overweight (25-<30 kg/m2), or obese (≥30 kg/m2). Self-reported and measured height, weight, and BMI were compared using mean differences and Bland-Altman plots and examined by sex, race/ethnicity, education, marital status, age group, and BMI category. Results: Men and women slightly overreported height and underreported weight. BMI calculated from self-reported data was lower than for measured data for men and women. In analyses stratified by race/ethnicity, age, education, and marital status, older women and women with less than a college degree overreported height. Approximately 13% of men and 7% of women were misclassified into a lower self-reported BMI category, with misclassification of BMI being greatest in obese men and women. Conclusions: Overall, height, weight, and BMI were well-reported, and this study further suggests that BMI computed from self-reported weight and height is a valid measure in men and women across different socio-demographic groups. [ABSTRACT FROM AUTHOR]

Higher body mass index (BMI; weight (kg)/height (m)2) is associated with increased risk of pancreatic cancer in epidemiologic studies. However, BMI has usually been assessed at older ages, potentially underestimating the full impact of excess weight. We examined the association between BMI and pancreatic cancer mortality among 963,317 adults who were aged 30–89 years at their enrollment in Cancer Prevention Study II in 1982. During follow-up through 2014, a total of 8,354 participants died of pancreatic cancer. Hazard ratios per 5 BMI units, calculated using proportional hazards regression, declined steadily with age at BMI assessment, from 1.25 (95% confidence interval: 1.18, 1.33) in persons aged 30–49 years at enrollment to 1.13 (95% confidence interval: 1.02, 1.26) in those aged 70–89 years at enrollment (P for trend = 0.005). On the basis of a hazard ratio of 1.25 per 5 BMI units at age 45 years, we estimated that 28% of US pancreatic cancer deaths among persons born in 1970–1974 will be attributable to BMI ≥25.0—nearly twice the equivalent proportion of those born in the 1930s, a birth cohort with much lower BMI in middle age. These results suggest that BMI before age 50 years is more strongly associated with pancreatic cancer risk than BMI at older ages, and they underscore the importance of avoiding excess weight gain before middle age for preventing this highly fatal cancer. [ABSTRACT FROM AUTHOR]

Background: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear.Methods: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided.Results: Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers.Conclusions: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract. [ABSTRACT FROM AUTHOR]

Summary: There is insufficient evidence linking excess body weight to risk of myeloid malignancies. We investigated this association using data from the Cancer Prevention Study‐II (CPS‐II), and a meta‐analysis of published cohort studies. Among 152 090 CPS‐II participants, 387 acute myeloid leukaemias (AML), 100 chronic myeloid leukaemias (CML) and 170 MDS were identified over 21 years of follow‐up. In CPS‐II, body mass index (BMI) was weakly associated with risk of CML (hazard ratio [HR] = 1·04, 95% confidence interval [CI]: 0·99–1·09 per 1 unit increase in BMI), AML (HR = 1·01, 95% CI: 0·98–1·03) and MDS (HR = 1·03, 95% CI: 0·99–1·07). After controlling for other anthropometric factors, no clear association was observed for height, BMI at age 18 years or weight change. In the meta‐analysis (n = 7117 myeloid leukaemias), BMI 25–29·9 kg/m2 (HRpooled = 1·36, 95% CI: 1·12–1·59) and BMI ≥30 kg/m2 (HRpooled = 1·43, 95% CI: 1·18–1·69) were associated with higher risk of myeloid leukaemia overall, compared to a BMI <25 kg/m2. Likewise, BMI ≥25 kg/m2 was positively associated with both AML and CML risk individually in the meta‐analysis. These results underscore the need for large studies to detect associations with rare cancers, and show a modest, but positive association between excess body weight and myeloid malignancy risk. [ABSTRACT FROM AUTHOR]

Introduction: Excess sitting is a risk factor for early mortality. This may be resulting, at least in part, from the displacement of physical activity with sedentary behaviors. The purpose of this observational study was to examine the mortality risk reductions associated with replacing 30minutes/day sitting for an equivalent duration of light or moderate to vigorous physical activity (MVPA).Methods: Participants included 37,924 men and 54,617 women in the Cancer Prevention Study-II Nutrition Cohort, of which 14,415 men and 13,358 women died during follow-up (1999-2014). An isotemporal substitution approach to the Cox proportional hazards regression model was used to estimate adjusted hazard ratios and 95% CIs for mortality associated with the substitution of 30minutes/day self-reported sitting for light physical activity or MVPA. Analyses were conducted in 2018.Results: Among the least active participants (≤17minutes/day MVPA), the replacement of 30minutes/day sitting with light physical activity was associated with a 14% mortality risk reduction (hazard ratio=0.86, 95% CI=0.81, 0.89) and replacement with MVPA was associated with a 45% mortality risk reduction (hazard ratio=0.55, 95% CI=0.47, 0.62). Similar associations were seen among moderately active participants (light physical activity replacement, hazard ratio=0.94, 95% CI=0.91, 0.97; MVPA replacement, hazard ratio=0.83, 95% CI=0.76, 0.88). However, for the most active (MVPA >38 minutes/day), substitution of sitting time with light physical activity or MVPA was not associated with a reduction in mortality risk (hazard ratio=1.00, 95% CI=0.97, 1.03, and hazard ratio=0.99, 95% CI=0.95, 1.02, respectively).Conclusions: These findings suggest that the replacement of modest amounts of sitting time with even light physical activity may have the potential to reduce the risk of premature death among less active adults. [ABSTRACT FROM AUTHOR]

Background: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health.Methods: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models.Results: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection.Conclusions: Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations. [ABSTRACT FROM AUTHOR]