Height as a mediator of sex differences in cancer risk.

BACKGROUND: Globally, age-standardized incidence rates for most cancers at shared sites are substantially and consistently higher in men than in women. Differences in established risk factors are unable to account for much of the sex disparity. We hypothesized that variability in height may be important in explaining sex differences in cancer risk. PATIENTS AND METHODS: We included 49 372 men from the Health Professionals Follow-up Study (1986-2014) and 115 612 women from the Nurses' Health Study (1980-2014). Height was reported at baseline and biennial questionnaires were used to collect information on cancer risk factors. We examined the association between sex and cancer incidence at shared anatomic sites using Cox proportional hazards models and performed mediation analysis to determine the percent of the association that was accounted for by height. RESULTS: Over up to 34 years of follow-up, 21 307 incident cases of cancers at shared sites (7705 men, 13 602 women) were documented. After adjusting for major cancer risk factors, men had a 39% increased risk of shared cancers overall (hazard ratio = 1.39; 95% confidence interval = 1.33-1.45) of which 35% (95% confidence interval = 24-46) was mediated by height. The excess risk of cancer for men was also partially explained by height for several specific cancers (gastrointestinal, melanoma, kidney, brain, hematologic). Mediation by height tended to be stronger among never smokers or those who adhered to a healthy lifestyle, and for cancers with fewer known environmental risk factors. CONCLUSIONS: Differences in height among men and women partially mediated the association between sex and cancer incidence at several shared sites. Hence, mechanisms underlying the relationship between height and cancer may be important determinants of sex disparities in cancer incidence.

Effect of long term aspirin use on the incidence of prostate cancer: A systematic review and meta-analysis.

BACKGROUND: Previous studies found divergent effects of aspirin use on prostate cancer incidence, potentially due to studies with short durations of aspirin use and insufficient adjustment for screening. METHODS: A systematic review on the association between aspirin use ≥3 years and incident prostate cancer was performed in accordance with the PRISMA and MOOSE criteria. RESULTS: In the cohort studies, aspirin use for at least 3 years was associated with a lower incidence rate of prostate cancer (Odds ratio (OR) 0.88, 95% CI 0.80-0.97). No protective association was established for the case-control studies (OR 0.92, 95% CI 0.68-1.23). Subgroup analysis of advanced and aggressive cancers showed a protective association (OR 0.82, 95% CI 0.71-0.94 and OR 0.75, 95% CI 0.61-0.97). CONCLUSION: This synthesis of observational studies suggests a potential protective association between long term aspirin use and incident prostate cancer. The current literature is highly heterogenous and suffers from inconsistent aspirin dose definition and measurement.

Heritability of the Number of Teeth in Middle-Aged and Older Danish Twins.

Tooth loss is a common health concern in older adults. We aimed to estimate the relative contributions of genetic and environmental factors to the variation in the number of teeth in middle-aged and older populations using a population-based cohort of Danish twins. The study included 5,269 Danish middle-aged or older twins who provided data on the number of teeth at baseline by structured interviews. The data were analyzed using univariate liability threshold modeling, stratified by sex and age, to estimate familial risk of tooth loss as well as estimates of heritability. In the whole cohorts, 23% of participants were edentate and 53% had retained 20 or more teeth. A statistical model including additive genetic factors and environmental factors partly shared by co-twins and partly unique to each individual twin gave the best statistical fit for the number of teeth in both age categories as well as in men and women. Overall, additive genetic factors explained 36% (95% confidence interval [CI]: 23% to 49%), common environmental factors 20% (95% CI: 9% to 31%), and unique environmental factors 44% (95% CI: 40% to 48%) of the total variation of the number of teeth. This study indicates that a substantial part of the variation in tooth loss is explained by genetic as well as environmental factors shared by co-twins. Our results implied that family background importantly affects tooth loss in both the middle-aged and the older populations. Family history is thus an important factor to take into account in dental health care.

Common variation in BRCA1 may have a role in progression to lethal prostate cancer after radiation treatment.

BACKGROUND: To evaluate whether single-nucleotide polymorphisms (SNPs) reflecting common variation in the tumor suppressor BRCA1 affect prostate cancer outcomes. Because radiation therapy (RT) induces DNA damage, we hypothesized that common variation in BRCA1 has a role in progression to lethal prostate cancer, particularly in patients receiving RT. METHODS: We followed 802 men diagnosed with localized prostate cancer (cT1-T3/N0/M0) who were treated with RT in the US Health Professionals Follow-up Study (HPFS) and Physicians' Health Study (PHS), for progression to lethal prostate cancer. Six SNPs (rs3737559, rs1799950, rs799923, rs915945, rs4474733 and rs8176305) were genotyped in HPFS to capture common variation across BRCA1. rs4474733 and rs8176305 were also evaluated in the PHS cohort. Cox proportional hazards models were used to estimate per-allele hazard ratios (HR) and 95% confidence intervals (CI) stratified by primary treatment. RESULTS: In the RT group (n=802), 71 men progressed to lethal disease during a mean follow-up of 12 years. We found that two SNPs, rs4473733 (HR: 0.65; 95% CI 0.42-0.99) and rs8176305 (HR: 2.03; 95% CI 1.33-3.10), were associated with lethal prostate cancer in men receiving RT. CONCLUSIONS: Common variation in BRCA1 may influence clinical outcomes in patients receiving RT for localized prostate cancer by modifying the response to RT. Our findings merit further follow-up studies to validate these SNPs and better understand their functional and biological significance.

Role of diet in prostate cancer: the epigenetic link.

Diet is hypothesized to be a critical environmentally related risk factor for prostate cancer (PCa) development, and specific diets and dietary components can also affect PCa progression; however, the mechanisms underlying these associations remain elusive. As for a maturing organism, PCa's epigenome is plastic and evolves from the pre-neoplastic to the metastatic stage. In particular, epigenetic remodeling relies on substrates or cofactors obtained from the diet. Here we review the evidence that bridges dietary modulation to alterations in the prostate epigenome. We propose that such diet-related effects offer a mechanistic link between the impact of different diets and the course of PCa development and progression.

Statins and prostate cancer recurrence following radical prostatectomy or radiotherapy: a systematic review and meta-analysis.

BACKGROUND: In this meta-analysis, we evaluated associations between statins and recurrence-free survival (RFS) following treatment of localized prostate cancer, with attention to potential benefits among patients treated primarily with radiotherapy (RT) versus radical prostatectomy. PATIENTS AND METHODS: We identified original studies examining the effect of statins on men who received definitive treatment of localized prostate cancer using a systematic search of the PubMed and EMBASE databases through August 2012. Our search yielded 17 eligible studies from 794 references; 13 studies with hazard ratios (HRs) for RFS were included in the formal meta-analysis. RESULTS: Overall, statins did not affect RFS (HR 0.90, 95% CI 0.74-1.08). However, in RT patients (six studies), statins were associated with a statistically significant improvement in RFS (HR 0.68; 95% CI 0.49-0.93); this benefit was not observed in radical prostatectomy patients (seven studies). Sensitivity analyses suggested that primary treatment modality may impact the effect of statins on prostate cancer recurrence. CONCLUSIONS: Our meta-analysis suggests a potentially beneficial effect of statins on prostate cancer patients treated with RT but not among radical prostatectomy patients. Although limited by the lack of randomized data, these results suggest that primary treatment modality should be considered in future studies examining associations between statins and oncologic outcomes.

No association between a polymorphic variant of the IRS-1 gene and prostate cancer risk.

OBJECTIVE: Insulin receptor substrate-1 (IRS-1) acts as a docking protein between the insulin-like growth factor-1 (IGF-1) receptor and intracellular signaling molecules in the IGF-1 signaling pathway. Accumulating data support a role of IGF-1 in prostate carcinogenesis. We assessed the influence of the most common IRS-1 gene polymorphism (Gly972Arg) on prostate cancer risk, alone and in combination with IGF-1 and other components in the IGF-1 signaling pathway. MATERIALS AND METHODS: In a nested case-control study within the Physicians' Health Study, the IRS-1 polymorphism was assayed from prospectively collected samples from 564 incident prostate cancer cases and 758 controls matched on age and smoking. We calculated relative risks (RR) and 95% confidence intervals (CI) using conditional logistic regression. RESULTS: Among the controls, 0.8% were homozygous (AA) and 12% were heterozygous (GA) for the polymorphic allele. There was no association between carriage of the A allele and total prostate cancer risk (RR = 1.1 95% CI = 0.8-1.5), advanced disease (stage C or D or lethal prostate cancer, RR = 1.3 95% CI = 0.8-2.3), or plasma IGF-1 levels. We explored possible interactions with body mass index and components in the IGF-1 pathway including IGFBP3, PI3k, and PTEN but none of these factors influenced the relation between IRS-1 genotype and prostate cancer risk. CONCLUSIONS: Our data do not support an association between carriage of the variant IRS-1 gene and prostate cancer risk.

MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden.

Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score > or =7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3-128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.

TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort.

The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3-5.8). Quantitative reverse-transcription-polymerase chain reaction demonstrated high ets-related [corrected] gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.

Environmental and heritable factors in the etiology of oral diseases--a population-based study of Swedish twins.

A population-based twin study is a useful design for quantification of the effects of genes and environmental factors in disease etiology. We used data from 10,000 Swedish twin pairs to quantify genetic and environmental contributions to tooth loss and periodontal health. Oral health information was obtained from telephone interviews. Structural equation models measured the relative importance of genetic and environmental factors. Genetic factors contributed to 14% of variation in tooth loss among women, and 39% among men. Non-shared environmental factors accounted for one-quarter of risk; environmental factors shared by twins comprised the remainder. Heritability estimates of periodontal disease were 39% and 33% for women and men, respectively, while non-shared environmental factors accounted for the remaining variation. Heritability for both conditions varied as a function of age and smoking status. Analysis of data from this large, population-based study demonstrates a moderate role of genetic factors in oral diseases, and suggests potential gene-environment interactions.

Effect of physician recommendation and patient adherence on rates of colorectal cancer testing.

This study explored: (1) patient characteristics associated with physician recommendation for colorectal cancer (CRC) screening and patient adherence to recommendation, and (2) the combined effect of recommendation and adherence on CRC testing, broadly defined. Data were from the 1999 MA BRFSS and a call-back survey of 869 BRFSS participants, age 50 and older. Logistic regression was used to identify correlates of recommendation, adherence, and testing. Patient-physician factors were positively associated with recommendation, adherence and testing. Inadequate health insurance was negatively associated with recommendation (OR = 0.45, 95% CI = 0.27-0.78) and testing (OR = 0.64, 95% CI = 0.38-1.1). Men were not more likely to be recommended (OR = 1.1, 95% CI = 0.78-1.5), but were more likely to adhere (OR = 1.9, 95% CI = 1.2-2.0) and to be tested (OR = 1.4, 95% CI = 1.0-1.9). There were gender differences in recommendation when considering health and risk factor measures. Research is needed to understand differences in recommendation and adherence. Greater encouragement and follow-through may be needed for groups less likely to adhere.

Diet during pregnancy in relation to maternal weight gain and birth size.

OBJECTIVE: Maternal weight gain has been consistently linked to birth weight but, beyond maternal energy intake, no macronutrient has been associated with either of them. We have examined whether maternal energy-adjusted intake of macronutrients is associated with either maternal weight gain or birth-size parameters. DESIGN: Cohort study. SETTING: University hospital in Boston, USA. SUBJECTS: A total of 224 pregnant women coming for their first routine prenatal visit. The women were followed through delivery. INTERVENTIONS: None. Pregnant women's dietary intake during the second trimester was ascertained at the 27th week of pregnancy through a food frequency questionnaire. RESULTS: Intake of neither energy nor any of the energy-generating nutrients was significantly associated with birth size. In contrast, maternal weight gain by the end of the second trimester of pregnancy was significantly associated with energy intake (+0.9 kg/s.d. of intake; P approximately 0.006) as well as energy-adjusted intake of protein (+3.1 kg/s.d. of intake; P<10(-4)), lipids of animal origin (+2.6 kg/s.d. of intake; P<10(-4)) and carbohydrates (-5.2 kg/s.d. of intake; P<10(-4)). CONCLUSIONS: Although maternal weight gain is strongly associated with birth size, the indicated nutritional associations with weight gain are not reflected in similar associations with birth-size parameters. The pattern is reminiscent of the sequence linking diet to coronary heart disease (CHD) through cholesterol: diet has been conclusively linked to blood cholesterol levels and cholesterol levels are conclusively linked to this disease, even though the association of diet with CHD has been inconclusive and controversial.

Correlates of colorectal cancer testing in Massachusetts men and women.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related death. Although CRC screening can reduce CRC mortality, it is underutilized. We examined the association between personal and health care characteristics and CRC testing, defined as being current on any test that meets CRC screening guidelines. METHODS: The current investigation relies on questionnaire data from the 1999 Massachusetts Behavioral Risk Factor Surveillance System and a CRC call-back survey of 869 Behavioral Risk Factor Surveillance System participants age 50 and older. Multivariate logistic regression was used to identify predictors of CRC testing. All analyses were stratified by gender. RESULTS: Men were more likely than women to be currently tested for CRC. Physician recommendation for testing was strongly associated with testing among men and women, but among those with a recommendation, men were more likely to be tested than women. Older age, usually having an annual check-up, and HMO membership were associated with CRC testing among men and women. Perceived high risk of CRC was more strongly associated with testing among men, while other cancer screening was more strongly associated with testing among women. CONCLUSIONS: There are important gender differences in the prevalence of CRC testing and in factors associated with testing. Research into understanding gender differences related to compliance with physician recommendations is warranted.

Dietary acrylamide and cancer of the large bowel, kidney, and bladder: absence of an association in a population-based study in Sweden.

Recently, disturbingly high levels of acrylamide were unexpectedly detected in widely consumed food items, notably French fries, potato crisps, and bread. Much international public concern arose since acrylamide has been classified as a probable carcinogen, although based chiefly on laboratory evidence; informative human data are largely lacking. We reanalysed a population-based Swedish case-control study encompassing cases with cancer of the large bowel (N=591), bladder (N=263) and kidney (N=133), and 538 healthy controls, assessing dietary acrylamide by linking extensive food frequency data with acrylamide levels in certain food items recorded by the Swedish National Food Administration. Unconditional logistic regression was used to estimate odds ratios, adjusting for potential confounders. We found consistently a lack of an excess risk, or any convincing trend, of cancer of the bowel, bladder, or kidney in high consumers of 14 different food items with a high (range 300-1200 microg kg(-1)) or moderate (range 30-299 microg kg(-1)) acrylamide content. Likewise, when we analysed quartiles of known dietary acrylamide intake, no association was found with cancer of the bladder or kidney. Unexpectedly, an inverse trend was found for large bowel cancer (P for trend 0.01) with a 40% reduced risk in the highest compared to lowest quartile. We found reassuring evidence that dietary exposure to acrylamide in amounts typically ingested by Swedish adults in certain foods has no measurable impact on risk of three major types of cancer. It should be noted, however, that relation of risk to the acrylamide content of all foods could not be studied.

The risk of liver and bile duct cancer in patients with chronic viral hepatitis, alcoholism, or cirrhosis.

No prospective study has analyzed simultaneously chronic viral hepatitis and alcoholism as risk factors for liver carcinogenesis, while taking into consideration the role of cirrhosis. Nor has the risk for hepatocellular carcinoma among patients with chronic viral hepatitis been prospectively evaluated in a low-risk Western population. Last, the relationship between hepatocellular carcinoma risk factors and bile duct cancer remains to be clarified. We analyzed prospectively the risk for primary liver and extrahepatic biliary tract cancer among 186,395 patients hospitalized with either chronic viral hepatitis, alcoholism, cirrhosis, or any combination of these conditions through linkages between national Swedish registers. Compared with the general population, the relative risk of hepatocellular carcinoma was 34.4 for chronic viral hepatitis alone, 2.4 for alcoholism alone, and 40.7 for cirrhosis alone. Among patients with combinations of these risk conditions, the relative risk of hepatocellular carcinoma was 27.3 for chronic viral hepatitis and alcoholism, 118.5 for chronic viral hepatitis and cirrhosis, 22.4 for alcoholism and cirrhosis, and 171.4 for all 3 conditions. We found limited evidence for an excess risk of intrahepatic, but not for extrahepatic, biliary duct cancer. Cirrhosis amplifies the risk of hepatocellular carcinoma among patients with chronic viral hepatitis, but it is not a prerequisite for liver carcinogenesis. In contrast, cirrhosis may be a necessary intermediate for the development of hepatocellular carcinoma among alcoholics.

Risk factors for cholangiocarcinoma in a low risk Caucasian population.

OBJECTIVES: Little is known about the etiology of cholangiocarcinoma, apart from its association with liver fluke infestation. METHODS: A case-control study was conducted in Athens and included six cholangiocarcinoma cases, 333 hepatocellular carcinoma cases and 360 controls with minor ailments or injuries. All subjects were interviewed and tested for hepatitis B and C infection. For all six cholangiocarcinomas, 97 hepatocellular carcinomas and 129 controls, sex steroids were determined in the blood. RESULTS: Hepatitis B or C viruses, tobacco smoking, alcohol drinking and diabetes mellitus were not related to cholangiocarcinoma, but history of thyroid disease was. Estradiol levels were higher among cholangiocarcinoma cases than among the other two groups. CONCLUSIONS: This study provides evidence that endocrine and autoimmune factors are important in the etiology of cholangiocarcinoma.

Support for condom availability and needle exchange programs among Massachusetts adults, 1997.

This study was conducted to determine whether demographic factors, variables related to HIV risk status, or personal attitudes predicted public support for condom availability programs in high schools and needle exchange programs. Data for these analyses were collected from the 1997 Massachusetts Behavioral Risk Factor Surveillance System (BRFSS) among adults aged 18-64. Overall, 79% of Massachusetts adults aged 18-64 supported condom availability programs, and 60% supported needle exchange programs. Younger age was the strongest demographic predictor of support for condom availability, and higher socioeconomic status was the strongest predictor of support for needle exchange programs. Support for both programs was weakly associated with personal HIV risk status but strongly associated with positive attitudes toward teaching about HIV in schools and advising sexually active teens to use condoms. Our data suggest that there is broad-based public support for implementation of condom availability and needle exchange programs as tools for HIV prevention.

Risk of cancers of the lung, head and neck in patients hospitalized for alcoholism in Sweden.

Alcoholic patients are at increased risk of cancers of the head and neck but little information is available on the magnitude of the risk for specific sites and for different histological types. We followed 182 667 patients with a hospital discharge diagnosis of alcoholism during 1965-1994, for an average of 10.2 years. We compared their incidence of site- and histological type-specific cancers of the oral cavity, pharynx, larynx and lung with that of the national population. The standardized incidence ratio (SIR) of cancer of the oral cavity and pharynx was 5.33 (95% confidence interval [CI] 5.04-5.64, based on 1207 cases). The SIRs of laryngeal and lung cancer were 4.21 (95% Cl 3.78-4.68, 347 cases) and 2.40 (2.29-2.51, 1880 cases), respectively. The SIR was highest for cancers of the hypopharynx, floor of the mouth, mesopharynx and base of the tongue. The relative excess of lung cancer was similar for squamous cell carcinoma and adenocarcinoma. Low age at first hospitalization was associated with higher SIRs for all sites under study. 25 years after first hospitalization for alcoholism, the cumulative probability of developing a lung cancer was in the order of 5%, for oral and pharyngeal cancer it was 2.5%, and for oesophageal or laryngeal cancer 1% each. Our study shows that the risk of head and neck cancer among heavy drinkers is highest for sites in direct contact with alcohol. The high risk of head and neck neoplasms may justify specific medical attention.

Dating violence against adolescent girls and associated substance use, unhealthy weight control, sexual risk behavior, pregnancy, and suicidality.

CONTEXT: Intimate partner violence against women is a major public health concern. Research among adults has shown that younger age is a consistent risk factor for experiencing and perpetrating intimate partner violence. However, no representative epidemiologic studies of lifetime prevalence of dating violence among adolescents have been conducted. OBJECTIVE: To assess lifetime prevalence of physical and sexual violence from dating partners among adolescent girls and associations of these forms of violence with specific health risks. DESIGN, SETTING, AND PARTICIPANTS: Female 9th through 12th-grade students who participated in the 1997 and 1999 Massachusetts Youth Risk Behavior Surveys (n = 1977 and 2186, respectively). MAIN OUTCOME MEASURES: Lifetime prevalence rates of physical and sexual dating violence and whether such violence is independently associated with substance use, unhealthy weight control, sexual risk behavior, pregnancy, and suicidality. RESULTS: Approximately 1 in 5 female students (20.2% in 1997 and 18.0% in 1999) reported being physically and/or sexually abused by a dating partner. After controlling for the effects of potentially confounding demographics and risk behaviors, data from both surveys indicate that physical and sexual dating violence against adolescent girls is associated with increased risk of substance use (eg, cocaine use for 1997, odds ratio [OR], 4.7; 95% confidence interval [CI], 2.3-9.6; for 1999, OR, 3.4; 95% CI, 1.7-6.7), unhealthy weight control behaviors (eg, use of laxatives and/or vomiting [for 1997, OR, 3.2; 95% CI, 1.8-5.5; for 1999, OR, 3.7; 95% CI, 2.2-6.5]), sexual risk behaviors (eg, first intercourse before age 15 years [for 1997, OR, 8.2; 95% CI, 5.1-13.4; for 1999, OR, 2.4; 95% CI, 1.4-4.2]), pregnancy (for 1997, OR, 6.3; 95% CI, 3.4-11.7; for 1999, OR, 3.9; 95% CI, 1.9-7.8), and suicidality (eg, attempted suicide [for 1997, OR, 7.6; 95% CI, 4.7-12.3; for 1999, OR, 8.6; 95% CI, 5.2-14.4]). CONCLUSION: Dating violence is extremely prevalent among this population, and adolescent girls who report a history of experiencing dating violence are more likely to exhibit other serious health risk behaviors.