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Purpose: Accumulating evidence suggests that light at night (LAN) disrupts circadian rhythms and may increase risk of liver cancer. However, there is no population-based study that examined LAN and liver cancer risk. Therefore, we aimed to investigate the association between outdoor LAN and liver cancer risk in a prospective cohort.Methods: Residential outdoor LAN level was measured from satellite imagery in the NIH-AARP Diet and Health Study, a prospective cohort of 451,945 men and women, 50-71 years old. Relative risks (RR) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models that adjusted for known risk factors for liver cancer and neighborhood characteristics.Results: During an average 12.2 years of follow-up, 897 liver cancers, 603 of which were hepatocellular carcinomas (HCC), were diagnosed. Residential outdoor LAN was not associated with risk of liver cancer (RRQ5 vs Q1 = 0.96, 95% CI: 0.77-1.20, p trend = 0.771) or HCC (RRQ5 vs Q1 = 0.82, 95% CI: 0.62-1.07, p trend = 0.425).Conclusion: No association between outdoor LAN and risk of liver cancer or HCC may in part be due to limitations in LAN assessment. More studies on the relationship between light intensity, duration, timing, and wavelength and liver cancer are warranted. [ABSTRACT FROM AUTHOR]

Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to generate receiver operating characteristic curves to compare the predictive ability of marker groups. After multivariable adjustment, HGF (Q4v1OR: 3.74; p-trend = 0.0001), SLAMF1 (Q4v1OR: 4.07; p-trend = 0.0001), CSF1 (Q4v1OR: 3.00; p-trend = 0.002), uPA (Q4v1OR: 3.36; p-trend = 0.002), IL-8 (Q4v1OR: 2.83; p-trend = 0.004), and OPG (Q4v1OR: 2.44; p-trend = 0.005) were all found to be associated with cirrhosis development compared to controls; these markers predicted cirrhosis with 69% accuracy. CDA analysis identified a nine marker model capable of predicting cirrhosis development with 79% accuracy. No markers were significantly different between HCC and cirrhotic participants. In this study, we assessed immunologic markers in relation to liver disease in chronically-HBV infected individuals. While validation in required, these findings highlight the importance of immunologic processes in HBV-related cirrhosis. [ABSTRACT FROM AUTHOR]

The relationship between dietary factors and liver disease remains poorly understood. This study evaluated the associations of whole grain and dietary fiber intake with liver cancer risk and chronic liver disease mortality. The National Institutes of Health–American Association of Retired Persons Diet and Health Study cohort recruited 485, 717 retired U.S. participants in 1995–1996. Follow-up through 2011 identified 940 incident liver cancer cases and 993 deaths from chronic liver disease. Compared with the lowest, the highest quintile of whole grain intake was associated with lower liver cancer risk (Hazard ratio [HR]Q5 vs. Q1 = 0.78, 95% confidence interval [CI]: 0.63–0.96) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.44, 95% CI: 0.35–0.55) in multivariable Cox models. Dietary fiber was also associated with lower liver cancer risk (HRQ5 vs. Q1 = 0.69, 95% CI: 0.53–0.90) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.37, 95% CI: 0.29–0.48). Fiber from vegetables, beans and grains showed potential protective effect. Here, we show that higher intake of whole grain and dietary fiber are associated with lower risk of liver cancer and liver disease mortality. Higher intake of dietary fiber and whole grains are associated with reduced risk of various diseases including some cancers. Here, the authors estimate reductions in liver cancer of 22% and 31% and chronic liver disease mortality of 56% and 63% associated with increased whole grain and dietary fiber intake, respectively. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the association between comorbidities and stage at diagnosis among NSCLC patients in the US Military Health System (MHS), which provides universal health care to its beneficiaries.Methods: The linked data from the Department of Defense's Central Cancer Registry (CCR) and the MHS Data Repository (MDR) were used. The study included 4768 patients with histologically confirmed primary NSCLC. Comorbid conditions were extracted from the MDR data. Comorbid conditions were those included in the Charlson Comorbidity Index (CCI) and were defined as a diagnosis during a 3-year time frame prior to the NSCLC diagnosis. Multivariable logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) of late stage (stages III and IV) versus early stage (stages I and II) in relation to pre-existing comorbidities.Results: Compared to patients with no comorbidities, those with prior comorbidities tended to be less likely to have lung cancer diagnosed at late stage. When specific comorbidities were analyzed, decreased odds of being diagnosed at late stage were observed among those with chronic obstructive pulmonary disease (COPD) (adjusted OR 0.78, 95% CI 0.68 to 0.90). In contrast, patients with a congestive heart failure or a liver cirrhosis/chronic hepatitis had an increased likelihood of being diagnosed at late stage (adjusted OR 1.30, 95% CI 1.00 to 1.69 and adjusted OR 1.87, 95% CI 1.24 to 2.82, respectively).Conclusions: Among NSCLC patients in an equal access health system, the likelihood of late stage at diagnosis differed by specific comorbid diseases. [ABSTRACT FROM AUTHOR]

Purpose: Periodontal disease, a major cause of tooth loss in adults, may have systemic effects and has been associated with higher risk of several cancer types. However, the associations of periodontal disease or tooth loss with liver cancer have only been examined prospectively in two studies, neither of which had sufficient statistical power. In addition, no studies assessed the potential confounding by viral hepatitis or Helicobacter pylori infection status.Methods: In this study, we examined the association between tooth loss and primary liver cancer incidence in a prospective cohort of Finnish male smokers (n = 29,096). We used Cox proportional hazards models to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs. As a sensitivity analysis, we conducted a nested case-control study within the original cohort to assess confounding by hepatitis B or C virus infection and seropositivity of H. pylori.Results: A total of 213 incident primary liver cancers occurred during a mean follow-up of 17 years. Among these cases, having 11-31 permanent teeth lost (HR 1.42, 95% CI 1.01-1.98) or all 32 teeth lost (HR 1.45, 95% CI 1.00-2.10) was each associated with higher risk of liver cancer, compared to those having 0-10 teeth lost. Adjusting for H. pylori seropositivity yielded a small attenuation of the effect estimate.Conclusions: Greater number of teeth lost was associated with higher risk of primary liver cancer in our study. The role of periodontal infection in the development of liver cancer warrants further investigation. [ABSTRACT FROM AUTHOR]

Incidence of non-alcoholic fatty liver disease (NAFLD) and liver cancer are 2–3 times higher in males than females. Hormonal mechanisms are hypothesized, with studies suggesting that oophorectomy may increase risk, but population-based evidence is limited. Thus, we conducted a study within the Clinical Practice Research Datalink, with controls matched to cases of NAFLD (n = 10,082 cases/40,344 controls) and liver cancer (n = 767 cases/3068 controls). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Effect measure modification by menopausal hormone therapy (MHT) was examined, using likelihood ratio tests and relative excess risk due to interaction (RERI). Oophorectomy was associated with a 29% elevated NAFLD risk (OR = 1.29, 95% CI 1.18–1.43), which was more pronounced in women without diabetes (OR = 1.41, 95% CI 1.27–1.57) and in women who had oophorectomy prior to age 50 (OR = 1.37, 95% CI 1.22–1.52). Compared to women without oophorectomy or MHT use, oophorectomy and MHT were each associated with over 50% elevated risk of NAFLD. However, the combination of oophorectomy and MHT showed evidence of a negative interaction on the multiplicative (p = 0.003) and additive scales (RERI = − 0.28, 95% CI − 0.60 to 0.03, p = 0.08). Oophorectomy, overall, was not associated with elevated liver cancer risk (OR = 1.16, 95% CI 0.79–1.69). These findings suggest that oophorectomy may increase the risk of NAFLD, but not liver cancer. [ABSTRACT FROM AUTHOR]

Purpose: The comparability between serum, plasma, and urinary measurements of estrogen metabolites via liquid chromatography-tandem mass spectrometry (LC-MS/MS) has not been largely explored, and it is unclear if urinary LC-MS/MS measurements are suitable surrogates of circulating levels.Methods: Serum, plasma (EDTA and heparin), and urinary estrogen/estrogen metabolite levels were measured via LC-MS/MS in paired samples from 64 healthy volunteers (18 men, 20 premenopausal women, 26 postmenopausal women). Geometric means and Spearman correlation coefficients were used to compare individual and combined pathway levels of estrogens/estrogen metabolites across biologic matrices by sex/menopausal status.Results: Measured concentrations of estrogens/estrogen metabolites across blood matrices were almost identical (percent differences < 4.8%). Parent estrogen concentrations measured in serum and urine were moderately correlated in postmenopausal women (estrone: r = 0.69, estradiol: r = 0.69). Correlations were similar comparing unconjugated serum estradiol to urinary estrone (r = 0.76) and urinary estradiol (r = 0.65) in postmenopausal women but were moderate to low in premenopausal women (r = 0.60, 0.40, respectively)/men (r = 0.33, 0.53, respectively). Comparing metabolite ratios, proportionally higher concentrations of 16-pathway metabolites were measured in urine versus serum across sex/menopausal status groups (e.g., postmenopausal women: 50.3% 16-pathway metabolites/total in urine versus 35.3% in serum).Conclusions: There is strong agreement between estrogen/estrogen metabolites measurements in serum, heparin plasma, and EDTA plasma. Individual estrogen metabolite concentrations were moderately correlated between urine and serum, but were not well correlated when evaluating pathway- or relative estrogen concentrations. Differences between serum and urine are likely explained by differences in metabolism and/or excretion. [ABSTRACT FROM AUTHOR]

Helicobacter has been suggested to play a possible role in hepatitis, gallstones, and hepatobiliary tumours. We assessed whether seropositivity to 15 H. pylori proteins was associated with subsequent incidence of 74 biliary tract and 105 liver cancer cases vs. 357 matched controls in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Odds ratios and 95% confidence intervals were computed by conditional logistic regression after adjustment for known hepatobiliary cancer risk factors. H. pylori seropositivity was not associated with either biliary tract (1.76, 0.90-3.46) or liver cancer (0.87, 0.46-1.65). CagA seropositivity was associated with both endpoints, although the latter association was not statistically significant (biliary tract: 2.16, 1.03-4.50; liver cancer: 1.96, 0.98-3.93) and neither association was statistically significant after correcting for multiple comparisons. Together, these results suggest possible associations between H. pylori and hepatobiliary cancer and suggest the value of future studies investigating the association.Trial registration number: NCT00339495. [ABSTRACT FROM AUTHOR]

Objective: In utero exposure to steroid hormones may be related to risk of some cancers such as testicular germ cell tumors (TGCT). To determine whether placental characteristics are good surrogate measures of maternal biomarker levels, we evaluated the correlations in mothers of sons at higher (whites, n = 150) and lower (blacks, n = 150) risk of TGCT. Associations with birth weight were also examined.Methods: All mothers, participants in the Collaborative Perinatal Project, were primigravidas who gave birth to male singletons. Associations between placental weight and placental thickness and third-trimester biomarker levels were evaluated using linear regression. Partial correlation coefficients for placental characteristics and birth weight were also estimated.Results: Placental weight was positively correlated with alpha-fetoprotein (AFP), sex hormone-binding globulin (SHBG), testosterone, estradiol and estriol in whites, and AFP and estriol in blacks. Placental thickness was not associated with any biomarker. After adjustment for placental weight, birth weight was not correlated with any biomarker.Conclusions: In these data, placental weight was modestly correlated with third-trimester biomarker level; however, it appeared to be a better surrogate for third-trimester biomarker level than birth weight. Placental thickness had limited utility as a surrogate measure for biomarker levels. [ABSTRACT FROM AUTHOR]

Background: Use of antibiotics could alter human microbiota composition and decrease bacterial diversity. Such microbial dysbiosis may have implications in hepatocarcinogenesis; however, the association between antibiotic use and liver cancer risk has been minimally examined in humans.Methods: We performed a nested case-control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom's Clinical Practice Research Datalink. Antibiotic use was obtained from prescription records. Multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using conditional logistic regression.Results: Ever-use of prescription antibiotics was associated with a slightly increased risk of liver cancer, compared to non-use (OR=1.22, 95% CI=1.03-1.45). However, there was no clear dose-response relationship by the number of prescriptions or cumulative dose of antibiotic use, suggesting a non-causal association.Conclusions: Our results do not support a role of antibiotic use in liver cancer development. [ABSTRACT FROM AUTHOR]

Obesity is implicated as an important factor in the rising incidence of liver cancer in the USA. Bariatric surgery is increasingly used for treating morbid obesity and comorbidities. Using administrative data from UHC, a consortium of academic medical centers in the USA, we compared the prevalence of liver cancer among admissions with and without a history of bariatric surgery within a 3-year period. Admissions with a history of bariatric surgery had a 61 % lower prevalence of liver cancer compared to those without a history of bariatric surgery (prevalence ratio 0.39, 95 % confidence interval 0.35-0.44), and these inverse associations persisted within strata of sex, race, and ethnicity. This hospital administrative record-based analysis suggests that bariatric surgery could play a role in liver cancer prevention. [ABSTRACT FROM AUTHOR]

Purpose: Unequal access to health care may be a reason for shorter survival among Black patients with renal cell carcinoma (RCC) than among their White counterparts. No studies have investigated survival disparity among RCC patients in an equal-access health care delivery system. This study aimed to examine racial differences in survival among clear cell RCC patients in the Department of Defense's (DoD) Military Health System (MHS), which provides equal access to care to all persons. Methods: The study used the DoD's Automated Central Tumor Registry to identify 2056 White patients and 370 Black patients diagnosed with clear cell RCC between 1988 and 2004. The subjects were followed through 2007 with a median follow-up time of 4.8 years. Kaplan-Meier survival curves were compared and a Cox model was used to estimate the hazard ratios (HRs) associated with survival by race. Results: During follow-up, 1,027 White and 158 Black patients died. The Kaplan-Meier curves showed that Black patients had more favorable overall survival than did White patients (log rank p = 0.031). After adjustment for demographic, tumor, and treatment variables, the Cox model showed no statistically significant racial difference overall (adjusted HR 1.07, 95 % CI 0.90-1.28) or stratified by age, sex or tumor stage. However, among patients who did not undergo surgery, Black patients had poorer survival than White patients. Conclusions: The lack of racial difference in survival among RCC patients in the MHS may be related to equal access to health care. Improved access could reduce the survival disparity among RCC patients in the general population. [ABSTRACT FROM AUTHOR]

Background: The number of lymph nodes examined during colon cancer surgery falls below nationally recommended guidelines in the general population, with Blacks and Hispanics less likely to have adequate nodal evaluation in comparison to Whites. The Department of Defense's (DoD) Military Health System (MHS) provides equal access to medical care for its beneficiaries, regardless of racial/ethnic background. This study aimed to investigate whether racial/ethnic treatment differences exist in the MHS, an equal-access medical care system. Methods: Linked data from the DoD cancer registry and administrative claims databases were used and included 2,155 colon cancer cases. Multivariate logistic regression assessed the association between race/ethnicity and the number of lymph nodes examined (<12 and ≥12) overall and for stratified analyses. Results: No overall racial/ethnic differences in the number of lymph nodes examined was identified. Further stratified analyses yielded similar results, except potential racial/ethnic differences were found among persons with poorly differentiated tumors, where non-Hispanic Blacks tended to be less likely to have ≥12 lymph nodes dissected (odds ratio 0.34; 95 % confidence interval 0.14-0.80; p = 0.01) compared with non-Hispanic Whites. Conclusion: Racial/ethnic disparities in the number of lymph nodes evaluated among patients with colon cancer were not apparent in an equal-access healthcare system. However, among poorly differentiated tumors there might be racial/ethnic differences in nodal yield, suggesting the possible effects of factors other than access to healthcare. [ABSTRACT FROM AUTHOR]

Background: Compared to non-inflammatory breast cancer (non-IBC), inflammatory breast cancer (IBC) has less favorable survival and is more likely to be estrogen receptor (ER) and progesterone receptor (PR) negative. ER−/PR− tumors, regardless of histology, have less favorable survival. While black women are more likely to have IBC and ER−/PR− tumors than white women, it is unclear whether the racial disparity in survival is explained by these factors. The objective of this study was to assess racial/ethnic differences in breast cancer survival by inflammatory status and hormone receptor status. Methods: This study examined breast cancer mortality among non-Hispanic white (NHW), Hispanic white, black, and Asian/Pacific Islander (API) women diagnosed between 1990 and 2004 using the National Cancer Institute's Surveillance, Epidemiology, and End Results data. Kaplan-Meier survival curves and Cox proportional hazard ratios (HRs) assessed the relationship between race/ethnicity and survival. Results: Black women had significantly poorer survival than NHW women regardless of inflammatory status and hormone receptor status. Compared to NHWs, the HRs for black women were 1.32 (95 % confidence interval (CI) 1.21-1.44), 1.43 (95 % CI 1.20-1.69), and 1.30 (95 % CI 1.16-1.47) for IBC, IBC with ER+/PR+, and with ER−/PR−, respectively. Similar HRs were found for non-IBC, non-IBC with ER+/PR−, and non-IBC with ER−/PR−. API women had significantly better survival than NHW women regardless of inflammatory status and hormone receptor status. Conclusion: Compared to NHW women, black women had poorer survival regardless of inflammatory status and hormone receptor status and API women had better survival. These results suggest that factors other than inflammatory status and hormone receptor status may play a role in racial/ethnic disparities in breast cancer survival. [ABSTRACT FROM AUTHOR]

OBJECTIVES:The objectives were to describe Surveillance, Epidemiology and End Results (SEER) hepatocellular carcinoma (HCC) incidence trends and the US liver cancer mortality trends by geography, age, race/ethnicity, and gender.METHODS:HCC incidence data from SEER 18 registries and liver cancer mortality data from the National Center for Health Statistics were analyzed. Rates and joinpoint trends were calculated by demographic subgroup. State-level liver cancer mortality rates and trends were mapped.RESULTS:HCC incidence rates in SEER registries did not significantly increase during 2007-2010; however, the US liver cancer mortality rates did increase. HCC incidence and liver cancer mortality rates increased among black, Hispanic, and white men aged 50+ years and decreased among 35-49-year-old men in all racial/ethnic groups including Asians/Pacific Islanders. Significantly increasing incidence and mortality rates among women were restricted to blacks, Hispanics, and whites aged 50+ years. Asian/Pacific Islander liver cancer mortality rates decreased during 2000-2010 with decreasing rates among women aged 50-64 years and men aged 35-49 years and stable rates in other groups. During 2006-2010, among individuals 50-64 years of age, blacks and Hispanics had higher incidence and mortality rates than Asians/Pacific Islanders. Liver cancer mortality rates were highest in Louisiana, Mississippi, Texas, and Washington, DC.CONCLUSIONS:Decreasing HCC incidence and liver cancer mortality rates among Asians/Pacific Islanders, men aged 35-49 years, and the nonsignificant increase in overall HCC incidence rates suggest that the peak of the epidemic may be near or have passed. Findings of geographic variation in mortality rates can inform control efforts. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States.METHODS:Persons ≥68 years diagnosed with HCC (n=6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5% random sample (n=255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95% confidence intervals (95% CI) and PAFs were calculated.RESULTS:As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95% CI: 36.29-43.84), HBV (OR 11.17, 95% CI: 9.18-13.59), alcohol-related disorders (OR 4.06, 95% CI: 3.82-4.32), rare metabolic disorders (OR 3.45, 95% CI: 2.97-4.02), and diabetes and/or obesity (OR 2.47, 95% CI: 2.34-2.61). The PAF of all factors combined was 64.5% (males 65.6%; females 62.2%). The PAF was highest among Asians (70.1%) and lowest among black persons (52.4%). Among individual factors, diabetes/obesity had the greatest PAF (36.6%), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%).CONCLUSIONS:The dominant risk factors for HCC in the United States among persons ≥68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor. [ABSTRACT FROM AUTHOR]

Objectives: While diabetes has been linked to several cancers in the gastrointestinal (GI) tract, findings have been mixed for sites other than colorectal and liver cancer. We used the Women's Health Initiative (WHI) data and conducted a comprehensive assessment of associations between diabetes and GI malignancy (esophagus, stomach, liver, biliary, pancreas, colon, and rectal). Methods: A total of 145,765 postmenopausal women aged 50-79 enrolled in the WHI were followed for a mean 10.3 years. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between GI cancers and diagnosed diabetes, including its duration and treatment. Results: Diabetes at enrollment was associated with increased risk of liver (HR = 2.97; 95 % CI, 1.66-5.32), pancreatic (HR = 1.62; 95 % CI, 1.15-2.30), colon (HR = 1.38; 95 % CI, 1.14-1.66), and rectal (HR = 1.87, 95 % CI: 1.22-2.85) cancer. Diabetes severity, assessed by duration or need for pharmacotherapy, appeared to have stronger links to risk of liver, pancreatic, and rectal cancer, but not colon cancer. There was no statistically significant association of diabetes with biliary, esophageal, and stomach cancers. Conclusion: Type 2 diabetes is associated with a significantly increased risk of cancers of the liver, pancreas, colon, and rectum in postmenopausal women. The suggestion that diabetes severity further increases these cancer risks requires future studies. [ABSTRACT FROM AUTHOR]

Despite a potential preventive effect of physical activity on hepatobiliary cancer, little information is available on the relation between the two. We studied the association between frequency of vigorous physical activity and hepatobiliary cancer among 507,897 participants of the NIH-AARP Diet and Health Study, aged 50-71 years at baseline in 1995/1996. During 10 years of follow-up, 628 incident cases of liver cancer and 317 cases of extrahepatic biliary tract cancer were registered. Physical activity levels were assigned according to the frequency of engagement in 20 min or more of vigorous physical activity per week: never/rarely (lowest level), less than once per week, 1-2 times per week, 3-4 times per week, 5 or more times per week (highest level). Using Cox regression, multivariate-adjusted relative risks (RR) comparing the highest with the lowest level of physical activity revealed a statistically significant decreased risk for liver cancer (RR = 0.64, 95 % confidence interval (CI) = 0.49-0.84, p-trend <0.001), particularly hepatocellular carcinoma (RR = 0.56, 95 % CI = 0.41-0.78, p-trend <0.001), independent of body mass index. By comparison, multivariate analyses indicated that physical activity was not statistically significantly associated with extrahepatic bile duct cancer (RR = 0.86, 95 % CI = 0.45-1.65), ampulla of Vater cancer (RR = 0.66, 95 % CI = 0.29-1.48), or gallbladder cancer (RR = 0.63, 95 % CI = 0.33-1.21). These results suggest a potential preventive effect of physical activity on liver cancer but not extrahepatic biliary tract cancer, independent of body mass index. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association of body size-captured via whole-body dual-energy X-ray absorptiometry (DXA) and physical measurement-with serum sex steroid hormones and sex hormone binding globulin (SHBG), we utilized cross-sectional data and serum samples from the National Health and Nutrition Examination Survey (NHANES; 1999-2004).Methods: Testosterone, androstanediol glucuronide (3-alpha-diol-G), estradiol, and SHBG were measured via immunoassay in serum samples from a total of 898 adult men (ages 20-90) participating in the morning examination. As part of the NHANES data collection, DXA scans and measurements of weight, height, and waist circumference were performed by trained staff. Linear regression was used to estimate associations between body size and hormone levels adjusted for potential confounders and NHANES sampling procedures.Results: Total bone area (cm(2)) was inversely associated with total testosterone (ng/mL) [beta = -0.12; p value < 0.01], while bone mineral density (g/cm(2)) was inversely associated with SHBG (nmol/L) [beta = -17.16; p value = 0.01]. Increased percent body fat was associated with lower concentrations of total testosterone [beta = -0.16; p value < 0.01] and SHBG [beta = -1.11; p value < 0.01] and higher concentrations of free estradiol (fg/mL) [beta = 12.52; p value < 0.01].Conclusions: Clinical measures of body fat (measured via DXA scan) and anthropometric measures of body fat (BMI and waist circumference) provided similar inferences regarding the association between increased body fat and hormone levels in men. Increased body fat was associated with lower circulating levels of testosterone (total and free) and SHBG and higher circulating levels of free estradiol in men, while decreased bone mineral density was associated with higher circulating levels of SHBG. [ABSTRACT FROM AUTHOR]

Purpose: The current working model of type II testicular germ cell tumor (TGCT) pathogenesis states that carcinoma in situ arises during embryogenesis, is a necessary precursor, and always progresses to cancer. An implicit condition of this model is that only in utero exposures affect the development of TGCT in later life. In an age-period-cohort analysis, this working model contends an absence of calendar period deviations. We tested this contention using data from the SEER registries of the United States.Methods: We assessed age-period-cohort models of TGCTs, seminomas, and nonseminomas for the period 1973-2008. Analyses were restricted to whites diagnosed at ages 15-74 years. We tested whether calendar period deviations were significant in TGCT incidence trends adjusted for age deviations and cohort effects.Results: This analysis included 32,250 TGCTs (18,475 seminomas and 13,775 nonseminomas). Seminoma incidence trends have increased with an average annual percentage change in log-linear rates (net drift) of 1.25 %, relative to just 0.14 % for nonseminoma. In more recent time periods, TGCT incidence trends have plateaued and then undergone a slight decrease. Calendar period deviations were highly statistically significant in models of TGCT (p = 1.24(-9)) and seminoma (p = 3.99(-14)), after adjustment for age deviations and cohort effects; results for nonseminoma (p = 0.02) indicated that the effects of calendar period were much more muted.Conclusion: Calendar period deviations play a significant role in incidence trends of TGCT, which indicates that postnatal exposures are etiologically relevant. [ABSTRACT FROM AUTHOR]

Introduction: Evidence from previous studies has suggested there may be physical and mental changes in health among testicular cancer survivors. No studies have been conducted in the United States, however. Methods: Study participants were initially enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005. A total of 246 TGCT (testicular germ cell tumor) cases and 236 non-testicular cancer controls participated in the current study, and completed a self-administered questionnaire. Mean time since diagnosis for cases was 14 years, and no less than five for all cases. Component scores determined from responses to questions about physical and mental health on SF36 were tabulated to yield two summary measures, physical component scores (PCS), and mental component scores (MCS). Component and summary scores were normalized to a score of 50 with a standard deviation of 10 by a linear T-score transformation. Results: Overall, cases may not suffer greatly in different quality of life than controls. When all cases and controls are compared, TGCT cases had lower PCS (mean: 51.9 95% CI: 50.6-53.2, P value: 0.037) than controls (mean: 53.6 95% CI: 52.7-54.6). MCS were not significantly different ( P value: 0.091). In multivariate analyses, several physical health components were worse for TGCT cases such as role-physical (OR 1.19, 95% CI: 1.01-1.39) and general health (OR 1.26, 95% CI: 1.07-1.49) compared to controls. However, TGCT cases treated with chemotherapy had lower PCS (cases: 50.2, 95% CI: 47.6-52.8; controls: 53.6, 95% CI: 52.7-54.6, P value: 0.0032) and MCS (cases: 49.3, 95% CI: 46.5-52.1; controls: 52.0, 95% CI: 50.9-53.2, P value: 0.039). TGCT cases who received treatments other than chemotherapy did not differ from controls in either PCS or MCS. Discussion: Physical and general health limitations may affect testicular cancer survivors. Men treated with chemotherapy, however, may be most likely to suffer adverse health outcomes due to a combination of body-wide effects on physical and mental factors which affect various aspects of physical health, mental health, and overall quality of life. And in particular, physical functioning, role-physical, and general health are strongly affected. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumors (TGCT) disproportionately affect men between the ages of 15 and 49 years, when reproduction is typical. Although TGCT treatment directly affects gonadal tissues, it remains unclear whether there are long-term effects on fertility. To examine post-TGCT treatment fertility, study participants in a previously conducted case-control study were contacted. The men were initially enrolled in the US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005. A total of 246 TGCT cases and 236 controls participated in the current study and completed a self-administered questionnaire in 2008–2009. TGCT cases were significantly more likely than controls to experience fertility distress (OR 5.23; 95% CI 1.99–13.76) and difficulty in fathering children (OR 6.41; 2.72–15.13). Cases were also more likely to be tested for infertility (OR 3.65; 95% CI 1.55–8.59). Cases, however, did not differ from controls in actually fathering children (OR 1.37; 95% CI 0.88–2.15). These findings were predominantly observed among nonseminoma cases and cases treated with surgery only or surgery-plus-chemotherapy. While expressing greater fertility distress, higher likelihood of fertility testing, and difficulty fathering children, these data suggest that TGCT survivors are no less likely to father children than are other men. It is possible that treatment for TGCT does not permanently affect fertility or, alternatively, that TGCT survivors attempt to father children with greater persistence or at younger ages than do other men. [ABSTRACT FROM AUTHOR]

The etiology of male breast cancer is largely unknown, reflecting its relative rarity. Although a number of previous studies have suggested relationships with a variety of medical conditions, the results have largely derived from case–control studies and may reflect recall biases. Within the large U.S. Veterans Affairs computerized medical care system database, we had the opportunity to access 26 million hospital discharge records over the period 1969–1996 and to relate various documented medical conditions to the risk of subsequent male breast cancer. This allowed us to calculate relative risks (RR) and 95% confidence intervals (CI) for male breast cancer associated with conditions occurring one or more years after initial hospitalization, adjusted for age, race, calendar year, duration of follow-up, and number of hospital visits. Among 4,501,578 men aged 18–100 years, a total of 642 cases of primary male breast cancer were identified (523 among whites, 119 among blacks). Medical conditions that were significantly related to risk were diabetes (RR 1.30, 95% CI 1.05–1.60), obesity (1.98, 1.55–2.54), orchitis/epididymitis (1.84, 1.10–3.08), Klinefelter syndrome (29.64, 12.26–71.68), and gynecomastia (5.86, 3.74–9.17). Additionally, among black patients, cholelithiasis emerged as a significant risk predictor (3.45, 1.59–7.47). Diseases that have previously been related to male breast cancer risk that were not supported by our study results included thyroid diseases, smoking-related conditions, liver cirrhosis, prostatic hyperplasia, and fractures. After adjustment for obesity, the association with diabetes disappeared, but that with gynecomastia persisted. In multivariate models that simultaneously considered all important medical predictors of risk, significant risks were seen for Klinefelter syndrome (16.83, 6.81–41.62), gynecomastia (5.08, 3.21–8.03), obesity (1.91, 1.50–2.44), and orchitis/epididymitis (1.80, 1.08–3.01). These results support previous speculations that male breast cancer is influenced not only by tissue at risk, but also by hormonal and inflammatory factors. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54-1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12-1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51-0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42-1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma. [ABSTRACT FROM AUTHOR]

Much evidence supports the premise that population genetic variation contributes significantly to the risk of testicular germ-cell tumor (TGCT). However, investigations of the association between genomic markers and TGCT susceptibility are scarce. Single nucleotide polymorphisms (SNPs) at the locus 8q24 have recently been found to be associated with prostate, colorectal and breast cancer. The US Servicemen’s testicular tumor environmental and endocrine determinants (STEED) study was used to investigate the association of 15 specific 8q24 SNPs with TGCT and its two main histologic groups of seminoma and nonseminoma. Conditional and unconditional logistic regression models, adjusted for the matching variables of year of birth, race/ethnicity and serum date, were utilized to produce odds ratios (OR) and 95% confidence intervals (95%CI). The analysis included 680 controls and 568 TGCT cases. In the TGCT analysis, no SNP was associated with risk in both heterozygotes and variant homozygotes. When stratified by histology the seminoma analysis also showed no association with the 8q24 SNPs. Conversely, the analysis of nonseminomas had three tentative associations (rs6470494, ORgenotype AG = 1.15, 95%CI: 0.86–1.54; ORgenotype GG = 1.68, 95%CI: 1.04–2.73; p for trend = 0.04) (rs13254738, ORgenotype GT = 1.04, 95%CI: 0.77–1.40; ORgenotype TT = 1.62, 95%CI: 1.06–2.49; p for trend = 0.07) (rs10505476, ORgenotype CT = 0.67, 95%CI: 0.50, 0.91; ORgenotype TT = 0.81, 95%CI: 0.47–1.39; p for trend = 0.04). There was no linkage disequilibrium between any of the 8q24 SNPs analyzed in this population. In conclusion, this study has found little evidence for an association between the reported 8q24 SNPs and TGCTs, although the findings for nonseminoma may be worth further investigation. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Population-attributable fractions of risk factors for hepatocellular carcinoma in the United states" in a previous issue of 2013 is presented.