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Despite decades of declining mortality rates, lung cancer remains the leading cause of cancer death in the United States. This article examines lung cancer incidence, stage at diagnosis, survival, and mortality using population‐based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Over the past 5 years, declines in lung cancer mortality became considerably greater than declines in incidence among men (5.0% vs. 2.6% annually) and women (4.3% vs. 1.1% annually), reflecting absolute gains in 2‐year relative survival of 1.4% annually. Improved outcomes likely reflect advances in treatment, increased access to care through the Patient Protection and Affordable Care Act, and earlier stage diagnosis; for example, compared with a 4.6% annual decrease for distant‐stage disease incidence during 2013–2019, the rate for localized‐stage disease rose by 3.6% annually. Localized disease incidence increased more steeply in states with the highest lung cancer screening prevalence (by 3%–5% annually) than in those with the lowest (by 1%–2% annually). Despite progress, disparities remain. For example, Native Americans have the highest incidence and the slowest decline (less than 1% annually among men and stagnant rates among women) of any group. In addition, mortality rates in Mississippi and Kentucky are two to three times higher than in most western states, largely because of elevated historic smoking prevalence that remains. Racial and geographic inequalities highlight longstanding opportunities for more concerted tobacco‐control efforts targeted at high‐risk populations, including improved access to smoking‐cessation treatments and lung cancer screening, as well as state‐of‐the‐art treatment. Recent declines in lung cancer mortality have outpaced those for incidence, reflecting gains in relative survival that are partly due to recent shifts to earlier stage at diagnosis. Persistent racial and geographic disparities reflect longstanding opportunities for public health intervention to reduce smoking and improve health care access. [ABSTRACT FROM AUTHOR]

Background: Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk‐prediction model (called SPLC‐RAT) was developed and validated using data from population‐based epidemiological cohorts and clinical trials, but real‐world validation has been lacking. The predictive performance of SPLC‐RAT was evaluated in a hospital‐based cohort of lung cancer survivors. Methods: The authors analyzed data from 8448 ever‐smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997–2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC‐RAT and further explored the potential of improving SPLC detection through risk model‐based surveillance using SPLC‐RAT versus existing clinical surveillance guidelines. Results: Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person‐years. The application of SPLC‐RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10‐year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC‐RAT development cohort), the observed SPLC incidence was significantly elevated in the high‐risk versus low‐risk subgroup (13.1% vs. 1.1%, p < 1 × 10–6). The risk‐based surveillance through SPLC‐RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow‐ups needed to detect one SPLC (162 vs. 202). Conclusion: In a large, hospital‐based cohort, the authors validated the predictive performance of SPLC‐RAT in identifying high‐risk survivors of SPLC and showed its potential to improve SPLC detection through risk‐based surveillance. Plain Language Summary: Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC).However, no evidence‐based guidelines for SPLC surveillance are available for lung cancer survivors.Recently, an SPLC risk‐prediction model was developed and validated using data from population‐based epidemiological cohorts and clinical trials, but real‐world validation has been lacking.Using a large, real‐world cohort of lung cancer survivors, we showed the high predictive accuracy and risk‐stratification ability of the SPLC risk‐prediction model.Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model‐based surveillance strategies compared to the existing consensus‐based clinical guidelines, including the National Comprehensive Cancer Network. Given the rapidly growing number of lung cancer survivors who are now at high risk of developing second primary lung cancer (SPLC), previous studies have identified SPLC risk factors and developed SPLC risk‐prediction models, but they lack insight into real‐world validation to help improve clinical decision‐making in SPLC surveillance for lung cancer survivors. Using a large, hospital‐based real‐world cohort of lung cancer survivors, the authors validated the predictive accuracy of an SPLC risk‐prediction model (area under the curve of 0.81), that can identify high‐risk lung cancer survivors for SPLC and can be incorporated into clinical decision‐making for SPLC surveillance to improve the systematic management of lung cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Helicobacter species (spp.) have been detected in human bile and hepatobiliary tissue Helicobacter spp. promote gallstone formation and hepatobiliary tumors in laboratory studies, though it remains unclear whether Helicobacter spp. contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to Helicobacter (H.) hepaticus or H. bilis proteins was associated with the development of hepatobiliary cancers in the Finnish Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study, and US‐based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Methods: We included 62 biliary and 121 liver cancers, and 190 age‐matched controls from ATBC and 74 biliary and 105 liver cancers, and 364 age‐ and sex‐matched controls from PLCO. Seropositivity to 14 H. hepaticus and H. bilis antigens was measured using a multiplex assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major hepatobiliary cancer risk factors and Helicobacter pylori serostatus. Results: Seropositivity to the H. bilis antigen, P167D, was associated with more than a twofold higher risk of liver cancer (OR: 2.38; 95% CI: 1.06, 5.36) and seropositivity to the H. hepaticus antigens HH0407 or HH1201, or H. bilis antigen, HRAG 01470 were associated with higher risk of biliary cancer (OR: 5.01; 95% CI: 1.53, 16.40; OR: 2.40; 95% CI: 1.00, 5.76; OR: 3.27; 95% CI: 1.14, 9.34, respectively) within PLCO. No associations for any of the H. hepaticus or H. bilis antigens were noted for liver or biliary cancers within ATBC. Conclusions: Further investigations in cohort studies should examine the role of Helicobacter spp. in the etiology of liver and biliary cancers. [ABSTRACT FROM AUTHOR]

Per‐ and polyfluoroalkyl substances (PFAS) are highly persistent endocrine‐disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case‐control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography‐tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype‐specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs [95% CIs] = 1.59 [1.01‐2.50], 2.34 [1.29‐4.23], and 2.19 [1.21‐3.98], respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER−, PR−, ER+/PR−, and ER−/PR− tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor‐positive tumors, and possibly between PFOA and receptor‐negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology. [ABSTRACT FROM AUTHOR]

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone‐binding globulin (SHBG) with aggressive, overall and early‐onset prostate cancer. In blood‐based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse‐variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08‐1.40). In blood‐based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02‐1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08‐1.34; blood‐based: 1.03, 1.01‐1.05) and early‐onset prostate cancer (MR: 1.37, 1.09‐1.73; blood‐based: 1.08, 0.98‐1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood‐based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups. [ABSTRACT FROM AUTHOR]

Background: Cancer incidence is higher in men than in women at most shared anatomic sites for currently unknown reasons. The authors quantified the extent to which behaviors (smoking and alcohol use), anthropometrics (body mass index and height), lifestyles (physical activity, diet, medications), and medical history collectively explain the male predominance of risk at 21 shared cancer sites.Methods: Prospective cohort analyses (n = 171,274 male and n = 122,826 female participants; age range, 50-71 years) in the National Institutes of Health-AARP Diet and Health Study (1995-2011). Cancer-specific Cox regression models were used to estimate male-to-female hazard ratios (HRs). The degree to which risk factors explained the observed male-female risk disparity was quantified using the Peters-Belson method.Results: There were 26,693 incident cancers (17,951 in men and 8742 in women). Incidence was significantly lower in men than in women only for thyroid and gallbladder cancers. At most other anatomic sites, the risks were higher in men than in women (adjusted HR range, 1.3-10.8), with the strongest increases for bladder cancer (HR, 3.33; 95% confidence interval [CI], 2.93-3.79), gastric cardia cancer (HR, 3.49; 95% CI, 2.26-5.37), larynx cancer (HR, 3.53; 95% CI, 2.46-5.06), and esophageal adenocarcinoma (HR, 10.80; 95% CI, 7.33-15.90). Risk factors explained a statistically significant (nonzero) proportion of the observed male excess for esophageal adenocarcinoma and cancers of liver, other biliary tract, bladder, skin, colon, rectum, and lung. However, only a modest proportion of the male excess was explained by risk factors (ranging from 50% for lung cancer to 11% for esophageal adenocarcinoma).Conclusions: Men have a higher risk of cancer than women at most shared anatomic sites. Such male predominance is largely unexplained by risk factors, underscoring a role for sex-related biologic factors. [ABSTRACT FROM AUTHOR]

Summary: Background: Non‐alcoholic fatty liver disease (NAFLD) is a major liver disease worldwide. Bile acid dysregulation may be a key feature in its pathogenesis and progression. Aims: To characterise the relationship between bile acid levels and NAFLD at the population level Methods: We conducted a cross‐sectional study in Guatemala in 2016 to examine the prevalence of NAFLD. Participants (n = 415) completed questionnaires, donated blood samples and had a brief medical exam. NAFLD was determined by calculation of the fatty liver index. The levels of 15 circulating bile acids were determined by LC–MS/MS. Adjusted prevalence odds ratios (PORadj) and 95% CI were calculated to examine the relationships between bile acid levels (in tertiles) and NAFLD. Results: Persons with NAFLD had significantly higher levels of the conjugated primary bile acids glycocholic acid (GCA) (PORadj T3 vs T1 = 1.85), taurocholic acid (TCA) (PORadj T3 vs T1 = 2.45) and taurochenodeoxycholic acid (TCDCA) (PORadj T3 vs T1 = 2.10), as well as significantly higher levels the unconjugated secondary bile acid, deoxycholic acid (DCA) (PORadj T3 vs T1 = 1.78) and its conjugated form, taurodeoxycholic acid (TDCA) (PORadj T3 vs T1 = 1.81). Conclusions: The bile acid levels of persons with and without NAFLD differed significantly. Among persons with NAFLD, higher levels of the conjugated forms of CA (i.e. GCA, TCA) and the secondary bile acids that derive from CA (i.e. DCA, TDCA) may indicate there is hepatic overproduction of CA, which may affect the liver via aberrant signalling mediated by the bile acids. [ABSTRACT FROM AUTHOR]

Background and Aims: Metabolic conditions such as obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in Guatemala and increase the risk for a number of disorders, including hepatocellular carcinoma (HCC). Aflatoxin B1 (AFB1) levels are also notably elevated in the population and are known to be associated with HCC risk. Whether AFB1 also contributes to the high prevalence of the metabolic disorders has not been previously examined. Therefore, the purpose of this study was to assess the association between AFB1 and the metabolic conditions. Methods: Four‐hundred twenty‐three individuals were included in the study, in which AFB1‐albumin adduct levels were measured in sera. Metabolic conditions included diabetes, obesity, central obesity, metabolic syndrome, and NAFLD. Crude and adjusted prevalence odds ratios (PORs) and 95% confidence intervals (95% CI) were estimated for the associations between the metabolic conditions and AFB1‐albumin adduct levels categorized into quartiles. Results: The study found a significant association between AFB1‐albumin adduct levels and diabetes (Q4 vs Q1 POR = 3.74, 95%CI: 1.71‐8.19; P‐trend.003). No associations were observed between AFB1‐albumin adduct levels and the other conditions. Conclusions: As diabetes is the metabolic condition most consistently linked to HCC, the possible association between AFB1 exposure and diabetes may be of public health importance. Further studies are warranted to replicate the findings and examine potential mechanisms. [ABSTRACT FROM AUTHOR]

Background and Aim: Previous studies suggest that serum ferritin may be associated with higher risk of liver cancer. However, additional studies of the association are needed. It is also not clear whether serum ferritin is associated with mortality from chronic liver disease (CLD). Methods: We performed a nested case–control study in the Linxian Nutrition Intervention Trials. Baseline serum ferritin was measured for 226 incident primary liver cancer cases, 281 CLD mortalities diagnosed, and 1061 age‐matched, gender‐matched, and trial‐matched controls. We used multivariable logistic regression models to calculate odds ratios and 95% confidence intervals. Subgroup analysis and interaction tests were performed by age, gender, alcohol drinking, hepatitis B virus seropositivity (HBV+)/hepatitis C virus seropositivity (HCV+), and trial. Results: Participants with serum ferritin in the highest quartile, as compared with those in the lowest quartile, had an increased risk of CLD mortality (odds ratio = 1.72, 95% confidence interval = 1.12, 2.64, P‐trend < 0.01). Moreover, the association with higher serum ferritin was stronger among alcohol drinkers and those who were HCV+ (P‐interaction < 0.05). For incident liver cancer, risk estimates were above one but were not statistically significant. Conclusion: In this study, higher levels of serum ferritin at baseline were associated with subsequent mortality from CLD, particularly if combined with alcohol drinking or viral hepatitis. Further work is warranted to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Prior studies have suggested that gastroesophageal reflux disease (GERD) may be associated with risk of squamous cancers of the larynx and esophagus; however, most of these studies have had methodological limitations or insufficient control for potential confounders. Methods: We prospectively examined the association between GERD and esophageal adenocarcinoma (EADC), esophageal squamous cell carcinoma (ESCC), and laryngeal squamous cell carcinoma (LSCC) in 490,605 participants of the NIH‐AARP Diet and Health Study cohort who were 50‐71 years of age at baseline. Exposure to risk factors were obtained from the baseline questionnaire. GERD diagnosis was extracted among eligible participants via linkage to Medicare diagnoses codes and then multiply imputed for non–Medicare‐eligible participants. Hazard ratios (HRs) and 95% CIs of GERD were computed using Cox regression. Results: From 1995 to 2011, we accrued 931 cases of EADC, 876 cases of LSCC, and 301 cases of ESCC in this cohort and estimated multivariable‐adjusted HRs of 2.23 (95% CI, 1.72‐2.90), 1.91 (95% CI, 1.24‐2.94), and 1.99 (95% CI, 1.39‐2.84) for EADC, LSCC, and ESCC, respectively. The associations were independent of sex, smoking status, alcohol intake, and follow‐up time periods. We estimated that among the general population in the United States, 22.04% of people aged 50‐71 years suffered from GERD. Using risk factor distributions for the United States from national survey data, 16.92% of LSCC cases and 17.32% of ESCC cases among individuals aged 50‐71 years were estimated to be associated with GERD. Conclusion: GERD is a common gastrointestinal disorder, but future prospective studies are needed to replicate our findings. If replicated, they may inform clinical surveillance of GERD patients and suggest new avenues for prevention of these malignancies. In a prospective cohort of 490,605 patients who were followed for 16 years, patients with a history of gastroesophageal reflux disease (GERD) have a 2‐fold higher risk of laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma. Moreover, an estimated 17% of these cancer cases were associated with GERD. If replicated by future prospective studies, it may inform clinical surveillance of GERD patients and provide new avenues for prevention of these malignancies. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested an association between Helicobacter pylori (H pylori) and nonalcoholic fatty liver disease (NAFLD). The aim of the current study was to examine the association in Guatemala, a region with elevated prevalences of both H pylori and NAFLD. Associations between H pylori and other metabolic conditions were also examined, as were associations between H hepaticus and H bilis and the metabolic conditions. Materials & Methods: The analysis included 424 participants from a cross‐sectional study in Guatemala. H pylori seropositivity was defined as positivity for ≥ 4 antigens. Seropositivities for H bilis and H hepaticus were defined as positivity for ≥ 2 antigens. NAFLD was estimated using the Fatty Liver Index and the Hepatic Steatosis Index. Other conditions examined were obesity, central obesity, hypercholesterolemia, low HDL, diabetes and metabolic syndrome (MetSyn). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated. Results: No overall associations between H pylori,H hepaticus, or H bilis and NAFLD or related metabolic conditions were found. Seropositivity for H pylori antigens CagA and VacA and H hepaticus antigen HH0713 was each significantly associated with NAFLD, however. In addition, associations were observed between the H pylori antigens HyuA, HP1564, and UreA and specified metabolic conditions. Conclusions: While no overall associations between H pylori or Helicobacter species with NAFLD or related conditions were observed, some selected Helicobacter spp. antigens were associated with NAFLD. Further research is warranted to examine whether H. species are associated with any metabolic condition. [ABSTRACT FROM AUTHOR]

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case–cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case–control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR Q1:Q4) for GNCA in NIT was 1.35 (95% CI: 0.89–2.05; p‐trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02–2.70; p‐trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR Q1:Q4 = 2.00, 95% CI: 1.45–2.77; p‐trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR Q1:Q4 = 0.65, 95% CI: 0.45–0.92; p‐trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence. What's new? Ghrelin, a stomach‐produced hormone, has numerous metabolic functions and possibly anti‐inflammatory properties. This is the first prospective epidemiologic study of circulating ghrelin conducted in China, a region with a very high burden of esophageal and gastric cancer. Low circulating ghrelin concentrations were associated with increased risk of both gastric noncardia adenocarcinoma and gastric cardia adenocarcinoma, which was consistent with previous findings in a Finnish population. Alterations in serum ghrelin levels occurred over 10 years before the development of clinically‐evident gastric and esophageal cancers. The findings highlight Ghrelin as a potential early marker for upper gastrointestinal cancer risk in regions of high incidence. [ABSTRACT FROM AUTHOR]

Cell‐mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking‐matched case–control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry‐based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20–30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15–1.75), 1.42 (1.14–1.76) and 1.45 (1.13–1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan–kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression. What's new? The kynurenine pathway, by which tryptophan is degraded and NAD+ is synthesized, plays a role in inflammation and immune response. It may also be involved in cancer development and progression. Here, the authors investigated the relationship between the metabolites of the kynurenine pathway and risk of lung cancer. They found that lower levels of tryptophan and higher levels of kynurenine and quinolinic acid were associated with increased risk of lung cancer, especially in smokers. These biomarkers may be signs that immune suppression in the tumor microenvironment may boost cancer progression. [ABSTRACT FROM AUTHOR]

Summary: Telomeres are essential for chromosomal stability and markers of biological age. We evaluated the effect of pre‐transplant short (<10th percentile‐for‐age) or very short (<5th or <1st percentile‐for‐age) leucocyte telomere length on survival after unrelated donor haematopoietic cell transplantation (HCT) for acquired severe aplastic anaemia (SAA). Patient pre‐transplant blood samples and clinical data were available at the Center for International Blood and Marrow Transplant Research. We used quantitative real time polymerase chain reaction to measure relative telomere length (RTL) in 490 SAA patients who received HCT between 1990 and 2013 (median age = 20 years). One hundred and twelve patients (22·86%) had pre‐HCT RTL <10th percentile‐for‐age, with the majority below the 5th percentile (N = 80, 71·43%). RTL <10th percentile‐for‐age was associated with a higher risk of post‐HCT mortality (hazard ratio [HR] = 1·78, 95% confidence interval [CI]=1·18–2·69, P = 0·006) compared with RTL ≥50th percentile; no survival differences were noted in longer RTL categories (P > 0·10). Time‐dependent effects for post‐HCT mortality were only observed in relation to very short RTL; HR comparing RTL <5th versus ≥5th percentile = 1·38, P = 0·15 for the first 12 months after HCT, and HR = 3·91, P < 0·0001, thereafter, P‐heterogeneity = 0·008; the corresponding HRs for RTL <1st versus ≥1st percentile = 1·29, P = 0·41, and HR = 5·18, P < 0·0001, P‐heterogeneity = 0·005. The study suggests a potential role for telomere length in risk stratification of SAA patients in regard to their HCT survival. [ABSTRACT FROM AUTHOR]

Insulin‐like growth factors (IGFs) and insulin‐like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross‐sectional associations of these exposures with circulating concentrations of IGFs (IGF‐I and IGF‐II) and IGFBPs (IGFBP‐1, IGFBP‐2 and IGFBP‐3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22–89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGF‐I, IGF‐II and IGFBP‐3. Higher body mass index was associated with lower concentrations of IGFBP‐1 and IGFBP‐2. Taller height was associated with higher concentrations of IGF‐I and IGFBP‐3 and lower concentrations of IGFBP‐1. Smokers had higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGFBP‐3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF‐II and lower concentrations of IGF‐I and IGFBP‐2. African Americans had lower concentrations of IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 and Hispanics had lower IGF‐I, IGF‐II and IGFBP‐3 than non‐Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk. What's new? In many cancers, evidence points to insulin‐like growth factors and their associated binding proteins as a possible culprit. This study investigated how IGF and IGF binding proteins correlate with various other cancer‐associated factors. The authors obtained data from 16,000 cancer‐free males ranging in age from 22 to 89 years. Their analysis confirmed associations between circulating IGFs and IGFBPs and age, race/ethnicity and BMI. They also uncovered some new associations, including with height, drinking alcohol and smoking. IGFs and their binding proteins, they suggest, may be part of the mechanism by which these factors influence cancer risk. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)‐Medicare data (1992–2013) to conduct a population‐based, case–control study. Cases (n = 32,443) had primary hepatobiliary cancer. Controls (n = 200,000) were randomly selected, cancer‐free adults frequency‐matched to cases by sex, age and year of selection. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with 39 autoimmune conditions identified via Medicare claims. We also conducted separate analyses for diagnoses obtained via inpatient versus outpatient claims. Sixteen conditions were associated with at least one hepatobiliary cancer. The strongest risk estimates were for primary biliary cholangitis with hepatocellular carcinoma (OR: 31.33 [95% CI: 23.63–41.56]) and primary sclerosing cholangitis with intrahepatic cholangiocarcinoma (7.53 [5.73–10.57]), extrahepatic cholangiocarcinoma (5.59 [4.03–7.75]), gallbladder cancer (2.06 [1.27–3.33]) and ampulla of Vater cancer (6.29 [4.29–9.22]). Associations with hepatobiliary‐related conditions as a group were observed across nearly all cancer sites (ORs ranging from 4.53 [95% CI: 3.30–6.21] for extrahepatic cholangiocarcinoma to 7.18 [5.94–8.67] for hepatocellular carcinoma). Restricting to autoimmune conditions diagnosed via inpatient claims, 6 conditions remained associated with at least one hepatobiliary cancer, and several risk estimates increased. In the outpatient restricted analysis, 12 conditions remained associated. Multiple autoimmune conditions are associated with hepatobiliary cancer risk in the US Medicare population, supporting a shared immuno‐inflammatory etiology to these cancers. What's new? Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. This large, longitudinal study investigated associations between hepatobiliary cancers and 39 autoimmune conditions. There was a 1.1‐ to 31.3‐fold increased risk of hepatobiliary cancer after diagnosis of a range of different autoimmune diseases, and novel associations were observed. The magnitude of associations was particularly strong for primary biliary cholangitis, primary sclerosing cholangitis, pure red cell aplasia and immune thrombocytopenic purpura. Findings support an immuno‐inflammatory etiology. Further research is needed to assess the need for additional cancer monitoring in individuals with certain autoimmune conditions. [ABSTRACT FROM AUTHOR]

The role of alcoholic beverages in the etiology of gastric cancer is unclear. Recent summaries showed a positive association between higher alcohol intake and gastric cancer risk, but the magnitude of association is small, there is moderate heterogeneity among studies, and most cases were from Asian populations. We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in 490,605 adults, aged 50–71 years at baseline who participated in the NIH‐AARP diet and health study. Alcohol consumption in the past year was assessed at baseline by questionnaire and defined as total grams of ethanol intake per day or as a categorical variable: nondrinker, up to or including one drink per day, one to three drinks per day and greater than three drinks per day. We used multivariable‐adjusted Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for associations between alcohol intake and risk of gastric adenocarcinomas. Through 2011, 662 incident cases of GCA and 713 of GNCA occurred. We found no association between higher alcohol consumption and GCA or GNCA, when examined as total alcoholic beverage intake or individual beverage types of beer, wine and liquor. Furthermore, we observed no association by stratum of sex, ethnic group, educational level or smoking status. We did, however, observe lower risk of GNCA among participants who drank up to one drink per day (HR = 0.81, 95% CI: 0.67–0.97) compared to nondrinkers. In conclusion, alcohol consumption was not associated with increased risk of GCA or GNCA in this large U.S. cohort. What's new? Alcohol appears not to raise risk of gastric cancer in an American population, a new study indicates. Recently, the World Cancer Research Fund International Continuous Update Project added stomach cancer to the list of alcohol‐caused cancers, based largely on studies of Asian populations. Yet East Asians are more likely to possess a genetic variant that affect alcohol metabolism and carcinogen formation. Here, the authors analyzed alcohol consumption reports and gastric cancer diagnoses from nearly 500,000 adults in the US, and found no association between risk of gastric adenocarcinoma and drinking alcohol. [ABSTRACT FROM AUTHOR]

Distal and proximal colon tumors have distinct incidence trends and embryonic origins; whether these sub‐sites have distinct susceptibilities to known risk factors is unclear. We used pooled data from 407,270 participants in three US‐based studies, with overall median follow‐up of 13.8 years. We used adjusted Cox models to analyze the association between dietary intakes (from diet history questionnaire) of total, processed and unprocessed red meat; total white meat, poultry and fish and meat‐related compounds: heme iron, nitrate, nitrite, the heterocyclic amines (HCAs) and benzo(a)pyrene (B(a)P) and incidence of colorectal cancer subsites. The risk of colorectal cancer (n = 6,640) increased by 35% for each 50 g/1,000 kcal higher daily intake of total red meat, with a significant right‐to‐left trend from proximal colon (HR: 1.24; 95% CI: 1.09–1.39) to distal colon (HR: 1.34; 95% CI: 1.13–1.55) and rectum (HR: 1.53; 95% CI: 1.28–1.79). Only unprocessed red meat showed a significant right‐to‐left trend. Each 50 g/1,000 kcal increase in white meat intake was associated with a 26% reduction in total colorectal cancer risk (HR: 0.74; 95% CI: 0.68–0.80), with a significant inverse right‐to‐left trend. The highest quintile of heme iron was associated with increased cancer risk only in the distal colon (HR: 1.20; 95% CI: 1.02–1.42) and rectum (HR: 1.27; 95% CI: 1.07–1.52). The highest quintile of HCAs, and nitrate/nitrite were associated with increased risk of total colorectal cancer, but these associations did not vary across anatomical subsites. In summary, right and left subsites of the colon may have distinct susceptibilities to meat and possibly other dietary risk factors, suggesting that the causes of colorectal cancer may vary across anatomical subsites. What's new? Tumors affecting the distal and proximal regions of the large intestine differ in incidence, in chromosomal and epigenetic alterations, and in embryonic origin. It remains uncertain, however, whether these subsites are also affected differently by known risk factors. This study shows that the intake of unprocessed red meat is associated with progressively increasing colorectal cancer risk from "right to left" – from the proximal colon to the distal colon. For meat‐related compounds, including nitrate/nitrite additives and heterocyclic amines produced during cooking, associations with colorectal cancer risk were similar across subsites. White meat intake was associated with reduced colorectal cancer risk. [ABSTRACT FROM AUTHOR]

Abstract: While liver cancer rates in the United States are increasing, 5‐year survival is only 17.6%, underscoring the importance of prevention. Physical activity has been associated with lower risk of developing liver cancer, but most studies assess physical activity only at a single point in time, often in midlife. We utilized physical activity data from 296,661 men and women in the NIH‐AARP Diet and Health Study cohort to test whether physical activity patterns over the life course could elucidate the importance of timing of physical activity on liver cancer risk. We used group modeling of longitudinal data to create physical activity trajectories using four time points across the life course from teenage years through middle age, identifying seven distinct trajectories. We then used Cox proportional hazards regression to assess the association between the physical activity trajectories and risk of hepatocellular carcinoma, the most common type of liver cancer. We found that, in adjusted analyses, compared to those with consistently low physical activity patterns, those who maintained activity levels over time had a 26–36% lower risk of liver cancer and those who increased physical activity over time had no associations with risk, while those who decreased activity over time had a nonsignificantly higher risk of liver cancer. Our results suggest that sustained physical activity is associated with lower risk of hepatocellular carcinoma, while increasing physical activity later in life may not yield the same benefit. Future research with larger sample sizes and more detailed data on dose and timing of physical activity may continue to yield insight into this association between physical activity and liver cancer risk. [ABSTRACT FROM AUTHOR]

An increasing proportion of US smokers smoke ≤10 cigarettes per day (CPD) or do not smoke every day, yet the health effects of low-intensity smoking are poorly understood. We identified lifelong smokers of <1 or 1-10 CPD and evaluated risk of incident cancer among 238,525 cancer-free adults, aged 59-82, in the NIH-AARP Diet and Health Study. A questionnaire administered in 2004-2005 assessed CPD during nine age-periods (<15 to ≥70). We estimated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable-adjusted Cox proportional hazards regression with age as the underlying time metric. Of the 18,233 current smokers, (7.6%), 137 and 1,243 reported consistently smoking <1 CPD and 1-10 CPD, respectively. Relative to never smokers, current smokers who reported consistently smoking 1-10 CPD over their lifetime were 2.34 (95% CI = 1.86-2.93) times more likely to develop smoking-related cancer. Current lifetime smokers of <1 CPD were 1.89 (95% CI = 0.90-3.96) times more likely to develop tobacco-related cancer, although the association did not reach statistical significance. Associations were observed for lifelong smoking of ≤10 CPD with lung cancer (HR = 9.65, 95% CI = 6.93-13.43); bladder cancer (HR = 2.22, 95% CI = 1.22-4.05); and pancreatic cancer (HR = 2.03, 95%CI: 1.05-3.95). Among lifelong ≤10 CPD smokers, former smokers had lower risks of smoking-related cancer with longer time since cessation and longer smoking duration. Lifelong <1 and 1-10 CPD smokers are at increased risk of incident cancer relative to never smokers and would benefit from cessation, providing further evidence that even low-levels of cigarette smoking cause cancer. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Rivera–Andrade et al papers. To view these articles, visit https://doi.org/10.1111/apt.16948 and https://doi.org/10.1111/apt.16962 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Rivera–Andrade et al papers. To view these articles, visit https://doi.org/10.1111/apt.16948 and https://doi.org/10.1111/apt.17041 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Rivera–Andrade et al papers. To view these articles, visit https://doi.org/10.1111/apt.16948 and https://doi.org/10.1111/apt.16986 [ABSTRACT FROM AUTHOR]

Previous studies have found associations between one-carbon metabolism nutrients and risk of several cancers, but little is known regarding upper gastrointestinal tract (UGI) cancer. We analyzed prediagnostic serum concentrations of several one-carbon metabolism nutrients (vitamin B12, folate, vitamin B6, riboflavin and homocysteine) in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers, which was undertaken in Finland between 1985 and 1988. We conducted a nested case-control study including 127 noncardia gastric adenocarcinoma (NCGA), 41 esophagogastric junctional adenocarcinoma and 60 esophageal squamous cell carcinoma incident cases identified within ATBC. Controls were matched to cases on age, date of serum collection and follow-up time. One-carbon nutrient concentrations were measured in fasting serum samples collected at baseline (up to 17 years prior to cancer diagnosis). Odds ratios and 95% confidence intervals (CI) were calculated using conditional logistic regression. Lower prediagnostic vitamin B12 concentrations at baseline were associated with a 5.8-fold increased risk of NCGA (95% CI = 2.7-12.6 for lowest compared to highest quartile, p-trend <0.001). This association remained in participants who developed cancer more than 10 years after blood collection, and after restricting the analysis to participants with clinically normal serum vitamin B12 (>300 pmol/L). In contrast, pepsinogen I, a known serologic marker of gastric atrophy, was not associated with NCGA in this population. As vitamin B12 absorption requires intact gastric mucosa to produce acid and intrinsic factor, our findings suggest vitamin B12 as a possible serologic marker for the atrophic gastritis that precedes NCGA, one more strongly associated with subsequent NCGA than pepsinogen. [ABSTRACT FROM AUTHOR]

Obesity relatively late in adulthood has been consistently associated with increased risk of primary liver cancer. However, little is known about the role of early adult adiposity and evolution of adiposity across adulthood in hepatocarcinogenesis. We examined adult body mass index (BMI; kg/m2) in relation to hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a large prospective cohort. Weight at ages 18, 35, 50 and at study baseline was retrospectively reported by 303,620 participants. BMI trajectories were identified using latent class trajectory modeling. Incidence of HCC and ICC was determined through 2011. Cox proportional hazards modeling was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 372 HCC cases and 104 ICC cases occurred during follow-up. Being obese (BMI ≥ 30) at ages 18, 35, 50 and at baseline (mean age 62.3 years, range 50.3-71.5 years) was associated with an 86-119% elevated risk of HCC. BMI trajectories that resulted in obesity were associated with ∼80% higher HCC incidence. BMI at age 18, per 5 kg/m2, was associated with a 34% higher risk of ICC, but the association attenuated for BMI at older ages. In conclusion, our findings suggest that maintaining a healthy BMI throughout the lifetime may reduce liver cancer risk. Future studies with longitudinally collected weight information are warranted to further elucidate the role of life-course adiposity in liver cancer development. [ABSTRACT FROM AUTHOR]

Several studies have reported bidirectional inverse associations between cancer and Alzheimer's disease ( AD) . This study evaluates these relationships in a Medicare population. Using Surveillance, Epidemiology, and End Results ( SEER) linked to Medicare data, 1992-2005, we evaluated cancer risks following AD in a case-control study of 836,947 cancer cases and 142,869 controls as well as AD risk after cancer in 742,809 cancer patients and a non-cancer group of 420,518. We applied unconditional logistic regression to estimate odds ratios ( ORs) and Cox proportional hazards models to estimate hazards ratios ( HRs). We also evaluated cancer in relation to automobile injuries as a negative control to explore potential study biases. In the case-control analysis, cancer cases were less likely to have a prior diagnosis of AD than controls ( OR = 0.86; 95% CI = 0.81-0.92). Cancer cases were also less likely than controls to have prior injuries from automobile accidents to the same degree ( OR = 0.83; 95% CI = 0.78-0.88). In the prospective cohort, there was a lower risk observed in cancer survivors, HR = 0.87 (95% CI = 0.84-0.90). In contrast, there was no association between cancer diagnosis and subsequent automobile accident injuries ( HR = 1.03; 95% CI = 0.98-1.07). That cancer risks were similarly reduced after both AD and automobile injuries suggest biases against detecting cancer in persons with unrelated medical conditions. The modestly lower AD risk in cancer survivors may reflect underdiagnosis of AD in those with a serious illness. This study does not support a relationship between cancer and AD. [ABSTRACT FROM AUTHOR]

Esophageal (EA) and esophagogastric junction (EGJA) adenocarcinoma have been steadily increasing in frequency in younger people; however, the etiology of these cancers is poorly understood. We therefore investigated associations of body mass index (BMI), cigarette smoking, alcohol consumption, gastroesophageal reflux and use of nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to age-specific risks of EA and EGJA. We pooled individual participant data from eight population-based, case-control studies within the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). The analysis included 1,363 EA patients, 1,472 EGJA patients and 5,728 control participants. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for age-specific (<50, 50-59, 60-69, ≥70 years) cancer outcomes, as well as interactions by age. BMI, smoking status and pack-years, recurrent gastroesophageal reflux and frequency of gastroesophageal reflux were positively associated with EA and EGJA in each age group. Early-onset EA (<50 years) had stronger associations with recurrent gastroesophageal reflux (OR = 8.06, 95% CI: 4.52, 14.37; peffect modification = 0.01) and BMI (ORBMI ≥ 30 vs. <25 = 4.19, 95% CI: 2.23, 7.87; peffect modification = 0.04), relative to older age groups. In contrast, inverse associations of NSAID use were strongest in the oldest age group (≥70 years), although this apparent difference was not statistically significant. Age-specific associations with EGJA showed similar, but slightly weaker patterns and no statistically significant differences by age were observed. Our study provides evidence that associations between obesity and gastroesophageal reflux are stronger among earlier onset EA cancers. [ABSTRACT FROM AUTHOR]

Helicobacter pylori ( H. pylori) infection is the strongest known risk factor for gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine whether seropositivity to 15 H. pylori proteins is associated with the subsequent development of noncardia gastric cancer in Linxian, China. We included 448 GNCA cases and 1242 controls from two time points within the Linxian General Population Nutrition Intervention Trial, Linxian. H. pylori multiplex seropositivity was defined as positivity to ≥4 of the 15 included antigens. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk factors. In addition, we undertook a meta-analysis combining H. pylori multiplex serology data from both time points. H. pylori multiplex seropositivity was associated with a significant increase in risk of GNCA at one time point (1985; OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56, 5.47). Combining data from both time points in a meta-analysis H. pylori multiplex seropositivity was associated with an increased risk of GNCA, as were six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was inversely associated with risk of GNCA. We identified six individual antigens that confer an increase in risk of GNCA within this population of high H. pylori seroprevalence, as well as a single antigen that may be inversely associated with GNCA risk. We further determined that the H. pylori multiplex assay provides additional information to the conventional ELISA methods on risk of GNCA. [ABSTRACT FROM AUTHOR]

Objective Studies of the fecal microbiome have implicated the gut microbiota in obesity, but few studies have examined the microbial diversity at other sites. The association between obesity and the upper gastrointestinal (UGI) microbial diversity was explored. Methods The UGI microbiome of 659 healthy Chinese adults with a measured body mass index (BMI) range of 15.0 to 35.7 was characterized using the 16S rRNA gene DNA microarray (HOMIM). Results In multivariate-adjusted models, alpha diversity was not associated with BMI. However, beta diversity, assessed by principal coordinate vectors generated from an unweighted UniFrac distance matrix of pairwise comparisons, was associated with BMI (third and fourth vectors, P = 0.01 and P = 0.03, respectively). Moreover, beta diversity, assessed by cluster membership (three clusters), was also associated with BMI; individuals in the first cluster [median BMI 22.35, odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.05-4.34] and second cluster [median BMI 22.55, OR = 0.26, 95% CI = 0.09-0.75] were significantly less likely to be obese (BMI ≥ 27.5) than those in the third cluster (median BMI 23.59). Conclusions A beta-diversity metric of the UGI microbiome is associated with a four fold difference in obesity risk in this Asian population. Future studies should address whether the UGI microbiome plays a causal role in obesity. [ABSTRACT FROM AUTHOR]

ABSTRACT The objective of this study was to examine the associations of reproductive factors and exogenous hormone use with risk of Parkinson's disease (PD) among postmenopausal women. The study comprised 119,166 postmenopausal women aged 50 to 71 years in the NIH-AARP Diet and Health Study, who completed a baseline questionnaire in 1995-1996 and a follow-up survey in 2004-2006. A total of 410 self-reported PD diagnoses were identified between 1995 and 2006. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. PD risk was not significantly associated with female reproductive factors including age at menarche, age at first live birth, parity, and age at menopause. For example, compared with women with natural menopause at age 50 to 54 years, the ORs were 1.18, (95% CI, 0.78-1.79) for women with natural menopause aged <45, 1.19 (95% CI, 0.88-1.61) for those aged 45 to 49, and 1.33 (95% CI, 0.91-1.93) for those aged 55 or older. We found that oral contraceptive use for ≥10 years (vs. never used) was associated with lower PD risk (OR, 0.59; 95% CI, 0.38-0.92), but shorter use showed no association. Use of menopausal hormone therapy showed inconsistent results. Compared with non-hormone users at baseline, current hormone users for <5 years showed a higher risk of PD (OR, 1.52; 95% CI, 1.11-2.08). However, no associations were observed for past hormone users or current users of ≥5 years. Overall, this large prospective study provides little support for an association between female reproductive factors and PD risk. Our findings on long-term oral contraceptive use and current hormone therapy warrant further investigations. © 2013 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the associations of reproductive factors and exogenous hormone use with risk of Parkinson's disease (PD) among postmenopausal women. The study comprised 119,166 postmenopausal women aged 50 to 71 years in the NIH-AARP Diet and Health Study, who completed a baseline questionnaire in 1995-1996 and a follow-up survey in 2004-2006. A total of 410 selfreported PD diagnoses were identified between 1995 and 2006. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. PD risk was not significantly associated with female reproductive factors including age at menarche, age at first live birth, parity, and age at menopause. For example, compared with women with natural menopause at age 50 to 54 years, the ORs were 1.18, (95% CI, 0.78-1.79) for women with natural menopause aged <45, 1.19 (95% CI, 0.88-1.61) for those aged 45 to 49, and 1.33 (95% CI, 0.91-1.93) for those aged 55 or older. We found that oral contraceptive use for ⩾10 years (vs. never used) was associated with lower PD risk (OR, 0.59; 95% CI, 0.38-0.92), but shorter use showed no association. Use of menopausal hormone therapy showed inconsistent results. Compared with non-hormone users at baseline, current hormone users for <5 years showed a higher risk of PD (OR, 1.52; 95% CI, 1.11-2.08). However, no associations were observed for past hormone users or current users of ⩾5 years. Overall, this large prospective study provides little support for an association between female reproductive factors and PD risk. Our findings on long-term oral contraceptive use and current hormone therapy warrant further investigations. [ABSTRACT FROM AUTHOR]

The aim of our study was to investigate whether intakes of total fat and fat subtypes were associated with esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cardia or gastric noncardia adenocarcinoma. From 1995-1996, dietary intake data was reported by 494,978 participants of the NIH-AARP cohort. The 630 EAC, 215 ESCC, 454 gastric cardia and 501 gastric noncardia adenocarcinomas accrued to the cohort. Cox proportional hazards regression was used to examine the association between the dietary fat intakes, whilst adjusting for potential confounders. Although apparent associations were observed in energy-adjusted models, multivariate adjustment attenuated results to null [ e.g., EAC energy adjusted hazard ratio (HR) and 95% confidence interval (95% CI) 1.66 (1.27-2.18) p for trend <0.01; EAC multivariate adjusted HR (95% CI) 1.17 (0.84-1.64) p for trend = 0.58]. Similar patterns were also observed for fat subtypes [ e.g., EAC saturated fat, energy adjusted HR (95% CI) 1.79 (1.37-2.33) p for trend <0.01; EAC saturated fat, multivariate adjusted HR (95% CI) 1.27 (0.91-1.78) p for trend = 0.28]. However, in multivariate models an inverse association for polyunsaturated fat (continuous) was seen for EAC in subjects with a body mass index (BMI) in the normal range (18.5-<25 kg/m2) [HR (95% CI) 0.76 (0.63-0.92)], that was not present in overweight subjects [HR (95% CI) 1.04 (0.96-1.14)], or in unstratified analysis [HR (95% CI) 0.97 (0.90-1.05)]. p for interaction = 0.02. Overall, we found null associations between the dietary fat intakes with esophageal or gastric cancer risk; although a protective effect of polyunsaturated fat intake was seen for EAC in subjects with a normal BMI. [ABSTRACT FROM AUTHOR]

Coffee drinking may be associated with reduced risk of endometrial cancer; however, prospective data are limited. Further, it is not clear whether any association between coffee and endometrial cancer differs according to coffee caffeine content. The association of coffee drinking with incidence of endometrial cancer was evaluated among 226,732 women, aged 50-71, enrolled in the NIH-AARP Diet and Health Study who completed a baseline epidemiologic questionnaire. Following a mean 9.3 years of follow-up, data were available for 1,486 incident endometrial cancer cases. Cox proportional hazards models were used to estimate associations of coffee with endometrial cancer incidence. Sub-group analyses were performed according to smoking status, hormone therapy use (HT) and body habitus. Coffee drinking was inversely related to incidence of endometrial cancer (hazard ratio [HR] comparing drinking of >3 cups/day versus no cups = 0.64, 95% CI, 0.51-0.80; Ptrend = 0.0004). The association of coffee with endometrial cancer risk was apparent for consumption of both regular (HR per cup = 0.90, 95% CI, 0.86-0.95) and decaffeinated coffee (HR per cup = 0.93, 95% CI, 0.87-0.99). The relation of coffee with endometrial cancer incidence varied significantly by HT use ( Pinteraction = 0.03) with an association only apparent among HT-never users (HR comparing drinking >3 cups/day versus no cups = 0.54, 95% CI, 0.41-0.72; Ptrend = 0.0005). Endometrial cancer incidence appears to be reduced among women that habitually drink coffee, an association that does not differ according to caffeine content. [ABSTRACT FROM AUTHOR]

There are several biologic mechanisms whereby coffee might reduce breast cancer risk. Caffeine and caffeic acid, major coffee constituents, have been shown to suppress mammary tumor formation in animal models and to inhibit DNA methylation in human breast cancer cells, respectively. Coffee may also reduce risk through decreasing inflammation and influencing estrogen metabolism. However, epidemiologic studies have been inconsistent and few studies have examined the association by estrogen and progesterone receptor (ER/PR) status. We evaluated coffee intake for its effect on incident breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort, which included 198,404 women aged 50-71 with no history of cancer, who in 1995-1996 completed a questionnaire capturing usual coffee intake over the past year. State cancer registry and mortality index linkage identified 9,915 primary incident breast carcinomas through December 2006; available information on hormone receptor (HR) status identified 2,051 ER+/PR+ and 453 ER−/PR− cancers. In multivariable proportional hazards models, coffee intake was not associated with breast cancer risk ( p-value for trend = 0.38; relative risk = 0.98, 95% confidence interval: 0.91-1.07, for four or more cups per day as compared to women who never drank coffee), and results did not vary by body mass index or history of benign breast biopsy ( p-value for interaction > 0.10). We found no evidence of a relationship with either caffeinated or decaffeinated coffee. Null findings persisted for risk of both HR-positive and -negative breast cancers. These findings from a large prospective cohort do not support a role of coffee intake in breast carcinogenesis. [ABSTRACT FROM AUTHOR]

The article reports on the study which establishes the association of menstrual and reproductive factors with the cancers in the upper gastrointestinal tract (UGI). It notes that the UGI tract cancers risks which involve the head and neck, esophagus, and stomach are higher in men to develop adenicarcinomas and squamous cell carcinomas. It implies that the higher levels of progesterone and estrogen levels in women could explain the lower incidence rates of UGI cancers in women than in men.

Squamous head and neck cancers include cancers of the oral cavity, pharynx and larynx are the sixth leading cause of cancer mortality worldwide, resulting in more than 350,000 deaths annually. Intake of fruit and vegetables may protect against head and neck cancer incidence, although few prospective studies have examined this association. We investigated this relation in 490,802 United States participants of the NIH-AARP Diet and Health cohort using Cox proportional hazard models adjusted for potential confounders. During 2,193,751 person years of follow-up from 1995/1996-2000, 787 participants were diagnosed with head and neck cancer. We found an inverse association between total fruit and vegetable intake and head and neck cancer risk (per serving/day/1,000 calories, Hazard Ratio, 95% Confidence interval: 0.94, 0.89-0.99). In models mutually adjusted for fruit and vegetable intake, the association was stronger for vegetables (fifth vs. first quintile: 0.65, 0.50-0.85) than for fruits (fifth vs. first quintile: 0.87, 0.68-1.11). When further subclassified into botanical groups, those in the highest tertile of leguminosae (dried beans, string beans and peas, 0.80, 0.67-0.96), rosaceae (apples, peach, nectarines, plums, pears and strawberries, 0.60, 0.49-0.73), solanaceae (peppers and tomatoes, 0.82, 0.69-0.98) and umbelliferae (carrots, 0.73, 0.60-0.89) had decreased risk of head and neck cancer, but no significant associations were seen for 9 other botanical groups. Results from this large prospective observational study are consistent with previous case-control studies and support the hypothesis that total fruit and vegetable intake is associated with reduced risk of head and neck cancer. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article focuses on the findings of a study that examined the association between cigarette smoking and cancers of the head and neck in women. The authors used age-standardized incidence rates and hazard ratios from Cox models adjusted for other risk factors for head and neck cancers. It notes that incidence rates of head and neck cancer were higher in male smokers than female smokers, but smoking may explain a higher proportion of head and neck cancer in women than in men.