Consumption of fruits,vegetables, and seaweeds (sea vegetables) and pancreatic cancer risk: The Ohsaki Cohort Study

Studies on the effects of consumption of fruits, vegetables, and seaweeds on the incidence of pancreatic cancer are not conclusive. We examined the association (if any) between the consumption of fruits, vegetables, and seaweeds and the risk of pancreatic cancer in Japan. Data from 32,859 participants registered in the Ohsaki National Health Insurance Cohort Study who were 40–79 years old and free of cancer at baseline were analyzed. Consumption of fruits, vegetables, and seaweeds was assessed at baseline using a self-administered food frequency questionnaire (containing 40 items). Incidences of pancreatic cancer were identified by computer linkage with the Miyagi Prefectural Cancer Registry. During 11 years of follow-up, 137 pancreatic cancers (67 men and 70 women) were identified. The hazard ratios (95% confidence interval) of pancreatic cancer risk for the highest versus the lowest tertile were 0.82 (0.40–1.68, trend P = 0.57) in men and 0.64 (0.35–1.20, trend P = 0.22) in women for total consumption of fruits, 0.89 (0.46–1.73, trend P = 0.76) in men and 0.67 (0.33–1.35, trend P = 0.23) in women for total consumption of vegetables, and 0.92 (0.46–1.84, trend P = 0.81) in men for consumption of seaweeds (results for the consumption of seaweeds in women were not analyzed because of poor reliability), respectively. Total consumption of fruits, vegetables, and seaweeds was not associated with a reduced risk of pancreatic cancer.     

Obesity,physical activity and cancer risks: Results from the Cancer,Lifestyle and Evaluation of Risk Study (CLEAR)

IntroductionPhysical activity (PA) has been associated with lower risk of cardiovascular diseases, but the evidence linking PA with lower cancer risk is inconclusive. We examined the independent and interactive effects of PA and obesity using body mass index (BMI) as a proxy for obesity, on the risk of developing prostate (PC), postmenopausal breast (BC), colorectal (CRC), ovarian (OC) and uterine (UC) cancers.MethodsWe estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for cancer specific confounders, in 6831 self-reported cancer cases and 1992 self-reported cancer-free controls from the Cancer Lifestyle and Evaluation of Risk Study, using unconditional logistic regression.ResultsFor women, BMI was positively associated with UC risk; specifically, obese women (BMI ≥30 kg/m²) had nearly twice the risk of developing UC compared to women with healthy-BMI-range (<25 kg/m²) (OR = 1.99;CI:1.31–3.03). For men, BMI was also positively associated with the risk of developing any cancer type, CRC and PC. In particular, obese men had 37% (OR = 1.37;CI:1.11–1.70), 113% (OR = 2.13;CI:1.55–2.91) and 51% (OR = 1.51;CI:1.17-1.94) higher risks of developing any cancer, CRC and PC respectively, when compared to men with healthy-BMI-range (BMI<25 kg/m²).Among women, PA was inversely associated with the risks of CRC, UC and BC. In particular, the highest level of PA (versus nil activity) was associated with reduced risks of CRC (OR = 0.60;CI:0.44–0.84) and UC (OR = 0.47;CI:0.27–0.80). Reduced risks of BC were associated with low (OR = 0.66;CI:0.51–0.86) and moderate (OR = 0.72;CI:0.57–0.91) levels of PA. There was no association between PA levels and cancer risks for men.We found no evidence of an interaction between BMI and PA in the CLEAR study.ConclusionThese findings suggest that PA and obesity are independent cancer risk factors.     

No association between garlic intake and risk of colorectal cancer

BackgroundAlthough experimental studies suggested beneficial role of garlic intake on colorectal carcinogenesis, limited prospective cohort studies have evaluated garlic intake in relation to colorectal cancer (CRC) incidence.MethodsWe followed 76,208 women in the Nurses’ Health Study and 45,592 men in the Health Professionals Follow-up Study for up to 24 years and examined garlic intake and garlic supplement use in relation to CRC risk. Information on garlic intake and supplement use was assessed using a validated food frequency questionnaire and a Cox proportional hazard regression model was used to estimate the multivariable hazard ratio (MV-HR) and 95% confidence intervals (95% CIs).ResultsWe documented 2368 (1339 women and 1029 men) incident CRC cases and found no association between garlic intake and CRC risk; the MV-HRs (95% CIs) associated with garlic (1 clove or 4 shakes per serving) intake ≥1/day compared with <1/month were 1.21 (0.94–1.57; p-trend = 0.14) for women and 1.00 (0.71–1.42; p-trend = 0.89) for men. The MV-HRs (95% CIs) of CRC for garlic supplement use, which was used in 6% of the participants in each study, were 0.72 (0.48–1.07) for women and 1.22 (0.83–1.78) for men.ConclusionOur prospective data do not support an important role of garlic intake or garlic supplement use in colorectal carcinogenesis.     

Body mass index and screening for colorectal cancer: gender and attitudinal factors

Background: Overweight/obese women and men are at increased risk for colorectal cancer (CRC) incidence and mortality. Research examining body mass index (BMI) and CRC screening has had mixed results. A clearer understanding of the extent to which high-BMI subgroups are screened for CRC is needed to inform planning for CRC screening promotions targeting BMI. Methods: Data were obtained from a random, population-based sample of women and men at average-risk for CRC (aged 50–75 years) during 2004 (n = 1098). Multiple logistic regression analyses were conducted to evaluate whether BMI category was significantly associated with the probability of reporting recent CRC screening and with the probability of agreeing with statements denoting attitudes/perceptions about CRC and screening. Attitudes/perceptions about CRC and screening were evaluated as potential mediators and moderators of the association between BMI category and CRC screening. Results: After controlling for characteristics associated with CRC screening, overweight and obese women were each 40% less likely to have CRC screening than women with normal-BMI (OR = 0.6, 95% CI:0.4–0.9 and OR = 0.6, 95% CI:0.3–0.9). BMI category was unrelated to screening among men. Obese women (but not men) were less aware than normal-BMI women that obesity increased risk for CRC (OR = 0.5, 95% CI:0.3–0.9) and less worried about CRC (OR = 0.5, 95% CI:0.3–0.8). However, findings suggest that attitudes/perceptions about CRC and screening did not mediate or moderate the association between BMI category and CRC screening. Conclusion: Overweight/obese women are at increased risk for CRC because of their greater BMI and their propensity not to screen for CRC. Study findings suggest that potentially modifiable perceptions, e.g., lack of awareness of risk for CRC and less worry about CRC, in this subgroup may not explain the relationship between BMI category and reduced screening.     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

The impact of PSA and digital rectal examination on the risk of prostate cancer specific mortality in men with a PSA level <2.5 ng/ml

IntroductionIt is unknown whether a normal range, diagnostic serum prostate specific antigen (PSA) level's influence on prostate cancer specific mortality (PCSM) is dependent upon digital rectal examination (DRE) findings.MethodsBetween 2004 and 2007, 9081 men diagnosed with non-palpable (T1c, N = 1710) or palpable (T2–T4, N = 7371) and non-metastatic prostate cancer (PC) were identified from surveillance, epidemiology, and end results data, selected based on pre-treatment PSA < 2.5 ng/ml. A multivariable competing risks regression model evaluated whether DRE findings interacted with PSA level in predicting risk of PCSM.ResultsAfter median follow-up of 2.83 years, 118 of 548 deaths (21.5%) were due to PC. Increasing diagnostic PSA was associated with increased risk of PCSM (AHR = 3.52; 95% CI: 1.25–9.89; P = .017) in men with T1c, Gleason score 7–10 PC, but decreased PCSM risk (AHR = 0.66; 95% CI: 0.52–0.83; P < .001) for men with T2–T4 PC and any Gleason score.DiscussionFor men with diagnostic PSA level <2.5 ng/ml and palpable PC, risk of early PCSM increases by 34% for a 1 point decrease in PSA from 2. This suggests the existence of clinically detectable, low PSA secreting disease with an elevated risk of early PCSM, highlighting the importance of the DRE in men with PC and normal range, diagnostic PSA.     

The functional −94 insertion/deletion ATTG polymorphism in the promoter region of NFKB1 gene increases the risk of sporadic colorectal cancer

Objective: To investigate the allele and genotype frequencies of NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism and to evaluate the association between the polymorphism and colorectal cancer (CRC) risk in Malaysian population. Methods: Genomic DNA was extracted from the peripheral blood samples of 474 study subjects, which consisted of 237 histopathologically confirmed CRC patients and an equal number of cancer-free controls. The NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed by DNA sequencing. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Results: The frequencies of wildtype (del/del), heterozygous (del/ins) and variant (ins/ins) genotypes in CRC patients were 31.7%, 53.6% and 14.8%, respectively, while those in cancer-free controls were 35.0%, 58.2% and 6.8%, respectively. The frequency of the variant genotype was significantly higher in cases compared to controls (P < 0.01). Evaluation of the risk association of the polymorphic genotypes revealed that the variant genotype could contribute to a significantly increased risk of CRC (OR = 2.42, 95% CI = 1.24–4.73, P < 0.01). Conclusions: The variant allele of NFKB1 ?94 ins/del ATTG (rs28362491) polymorphism is associated with higher risk of sporadic CRC in Malaysian population.     

Impact of HLA-class I alleles on response to HCV treatment in a cohort of Egyptian patients

Extensive allele diversity is observed in HLA associations with response to HCV combined therapy (pegylated interferon + ribavitin) in different global ethnic populations. The aim of the study is to assess the frequency and association of certain HLA-class I alleles in Egyptian persons with persistent HCV and others with sustained viral response (SVR).Material and methodsThe study was a retrospective cohort study that included 246 HCV patients who received combined therapy; 106 cases responded to treatment (SVR) and 140 individuals did not respond to treatment (persistent HCV infection). Both groups are subjected to genotyping for HLA-class I.ResultsAccording to logistic regression analysis, Cw17 was considered as the most predictor allele as it was the highest significant allele (OR = 16.70; 95% CI: 2.64–105.58; P = 0.003), whereas the presence of the HLA-B45 and HLA-B27 alleles has a 19.35-fold risk and 15.7 fold risk, respectively of non-response to interferon therapy in chronic HCV patients (OR = 19.35; 95% CI: 1.05–357.24; P = 0.04) and (OR = 15.69; 95% CI: 1.179–208.9; P = 0.04) can act also as high predictor alleles, and the lowest significant predictor allele was B44 (OR = 6.535; 95% CI: 1.55–27.63; P = 0.01). The presence of the HLA-A alleles might have a limited role in prediction for the non-responders, as the A32 was significantly higher among the SVR patients, but, it cannot have a predictor role (OR: 0.161, CI: 0.03–1.056, P = 0.049).ConclusionCw17, HLA-B45, and HLA-B27 alleles can predict the nonresponders to HCV combined therapy.     

Polymorphisms in methyl-group metabolism genes and risk of sporadic colorectal cancer with relation to the CpG island methylator phenotype

Background: The CpG island methylator phenotype (CIMP), together with extensive promoter methylation, is regarded as one of the mechanisms involved in colorectal carcinogenesis. The mechanisms underlying CIMP in sporadic colorectal cancer are poorly understood. Genes involved in methyl-group metabolism are likely to affect DNA methylation and thereby influence an individual's risk of CIMP. The aim of the present study was to evaluate whether polymorphisms in the genes encoding methyl-group metabolism pathway predispose to CIMP+ and/or CIMP? CRC. Methods: We examined the potential association between the polymorphisms of MTHFR 677C>T, TS 5′UTR 2R/3R, TS 3′UTR 1494del6, ΔDNMT3B ?149C>T and DNMT3B ?283T>C in a group of 46 CIMP+ CRC cases, 140 CIMP? CRC cases and 140 healthy controls. The CIMP status of the CRC cases was determined by MS-PCR in tumor tissue by a panel of five markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1), which was also followed by analyzing hMLH1 methylation and BRAF V600E mutation. Results: The variant allele homozygote genotype for the ΔDNMT3B ?283T>C polymorphism was associated with a decreased risk for CIMP+ CRC (OR: 0.31, 95%CI: 0.09–0.73, p = 0.009). Individuals with TS 3R/3R had an increased risk of CIMP? CRC (OR: 2.21, 95%CI: 1.23–4.91, p = 0.01). Moreover, the carriers of 3R allele had an increased risk of CIMP? CRC (OR: 1.45, 95%CI: 1.10–2.13, p = 0.01). Conclusion: This study provides support to the hypothesis that methyl-group metabolism plays a role in the etiology of both CIMP+ and CIMP? colorectal cancers but has a different impact on a distinct molecular subgroups of colorectal cancer.     

Prediction of all-cause mortality with copeptin in cardio-cerebrovascular patients: A meta-analysis of prospective studies

BackgroundMeasurement of the biomarker copeptin may help identify disease severity and risk of mortality for a various diseases. This study sought to determine the relationship between copeptin and all-cause mortality of patients with cardio-cerebrovascular disease.MethodsDatabase of Medline and Web of Science were searched for studies with data involving the baseline copeptin levels and subsequent all-cause mortality outcomes. The pooled HRs of all-cause mortality were calculated and presented with 95%CIs. Subgroup analysis and sensitivity analysis were conducted to explore the possible sources of heterogeneity.ResultsData from 14,395 participants were derived from 28 prospective studies. Higher copeptin significantly increased the risk of all-cause mortality (per unit copeptin: HR = 1.020, 95%CI = 1.004–1.036; log unit copeptin: HR = 2.884, 95%CI = 1.844–4.512; categorical copeptin: HR = 3.371, 95%CI = 2.077–5.472). Subgroup analysis indicated that the risk of all-cause death was higher in cerebrovascular patients (per unit copeptin: HR = 2.537, 95%CI = 0.956–6.731; log unit copeptin: HR = 3.419, 95%CI = 2.391–4.888) than cardiovascular patients (per unit copeptin: HR = 1.011, 95%CI = 1.002–1.020; log unit copeptin: HR = 2.009, 95%CI = 1.119–3.608).ConclusionCopeptin is associated with all-cause mortality of patients with cardiovascular and cerebrovascular disease. Our study suggests that copeptin seems to be a promising novel biomarker for prediction of mortality in cardio-cerebrovascular patients, especially for cerebrovascular patients.     

An updated meta-analysis on the association of TGF-β1 gene promoter -509C/T polymorphism with colorectal cancer risk

AimPublished data on the association between transforming growth factor-β1 (TGF-β1) gene promoter-509C/T polymorphism and colorectal cancer (CRC) risk are inconsistent and inconclusive. To derive a more precise estimation of this association, a meta-analysis was carried out.MethodsMeta-analysis was performed to evaluate reported studies of the relationship between TGF-β1 gene promoter-509C/T polymorphism and colorectal cancer risk using fixed-effects model and random-effects model.ResultsWe observed an increased colorectal cancer risk among subjects carrying TGF-β1 gene promoter-509CC + CT genotype (odds ratio (OR) = 1.18%, 95% confidence interval (95% CI): 1.06–1.32) using 4440/6785 cases/controls in total population. We observed an increased risk of the TGF-β1 gene promoter -509CC, CT and CC + CT polymorphisms for colorectal cancer in population-based study (OR = 1.36, 95% CI: 1.19–1.56, OR = 1.18, 95% CI: 1.03–1.34 and OR = 1.26, 95% CI: 1.12–1.43, respectively) in stratified analysis. We observed an increased colorectal risk among CC and CC + CT carriers in European and American population (OR = 1.22, 95% CI: 1.04–1.43 and OR = 1.18, 95% CI: 1.02–1.38, respectively). We also observed an increased risk of colon cancer among subjects carrying CC + CT genotype (OR = 1.31, 95% CI: 1.05–1.63).ConclusionsThe present meta-analysis results suggest that TGF-β1 gene promoter -509C allele variant is a possible risk factor for developing colorectal cancer. Recommendations for further studies include pooling of individual data to verify results from the study and to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.     

A higher prediagnostic insulin level is a prospective risk factor for incident prostate cancer

A higher insulin level has been linked to the risk of prostate cancer promotion. However, several reports claim that there is no association between a higher insulin level and the risk of incident prostate cancer. In the present report, the insulin hypothesis was tested once more prospectively in men with a benign prostatic disorder. Three hundred and eighty-nine consecutive patients referred with lower urinary tract symptoms without clinical prostate cancer were included during 1994–2002. Follow-up was performed in 2006. Data were obtained from the Swedish National Cancer Register and the Regional Cancer Register, Oncological Centre, Göteborg, Sweden. At this follow-up, 44 of the patients included had developed prostate cancer. Men with prostate cancer diagnosis had a higher systolic (P < 0.001) and diastolic blood pressure (P < 0.000), were more obese as measured by BMI (P = 0.010), waist (P = 0.007) and hip measurements (P = 0.041) than men who did not have prostate cancer diagnosis at follow-up. These men also had a higher uric acid level (P = 0.040), and a higher fasting serum insulin level (P = 0.023) than men who did not have prostate cancer diagnosis at follow-up. Following exclusion of T1a/b prostate cancer cases, the difference of the fasting serum insulin level between the groups was still significant (P = 0.038). Our data support the hypothesis that a higher insulin level is a promoter of prostate cancer. Moreover, our data suggest that the insulin level could be used as a marker of the risk of developing prostate cancer. The present findings also seem to confirm that prostate cancer is a component of the metabolic syndrome. Finally, our data generate the hypothesis that the metabolic syndrome conceals early prostate cancer.     

Glutathione S-transferase polymorphisms and survival in African-American and White colorectal cancer patients

Background: Glutathione S-transferase (GST) enzymes are involved in electrophile detoxification. The authors investigated the association between GST genotype and survival in a racially diverse, population-based cohort of colorectal cancer (CRC) patients followed for a median of 9.6 years. Methods: Interviews were conducted with 315 African-American and White CRC patients in Connecticut, 1987–1991. Tumor tissue (n = 197) was later retrieved from hospital of diagnosis and assayed using multiplex PCR (GSTM1 and GSTT1) and PCR and RFLP analysis (GSTP1). Cox proportional hazards models provided adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Individuals with Ile/Val or Val/Val GSTP1 genotypes had a decreased risk of death (multivariate adjusted HR = 0.72, 95% CI: 0.48, 1.09) relative to those with wild type (Ile/Ile). Among those who received chemotherapy, this benefit was more pronounced (HR = 0.35, 95% CI: 0.16, 0.79); the interaction of reduced function GSTP1 genotype and chemotherapy was significant (P = 0.05). GSTM1 and GSTT1 genotype were not associated with survival. GSTM1, GSTT1, and GSTP1 genotype did not vary by race and did not contribute significantly to the survival disadvantage observed in African-Americans. Conclusions: In summary, GSTP1 genotype may play a role in CRC survival in African-Americans and Whites, particularly among those who receive chemotherapy.     

Trends and inequities in colorectal cancer screening participation in Ontario,Canada, 2005–2011

Background: Participation in screening tests for colorectal cancer (CRC) is generally low in Ontario, Canada. In addition, inequities in participation exist including lower participation among low-income individuals, males and individuals living in rural areas. In April 2008, Colon Cancer Check (CCC) program, the province-wide CRC screening program, was launched in Ontario. This study describes the trends and inequities in CRC screening participation three years before and three years after the CCC, and assesses the effect of the program on CRC screening participation, overall and among certain population groups. Methods: We used administrative data to identify cohorts of individuals eligible for CRC screening in fiscal years 2005–2011. We calculated the age-standardized percent of Fecal Occult Blood Test (FOBT) participation, large bowel endoscopy participation, and being ‘up-to-date’ with CRC screening tests. Results: From 2005 to 2011, FOBT participation increased from 7.6% to 14.8%, large bowel endoscopy participation from 3.4% to 5.7%, and ‘up-to-date’ with CRC screening from 27.2% to 41.3%. Before the launch of the CCC program, the quarterly increase in FOBT participation was 0.07% (p = 0.19), increased immediately after the launch (1.8%, p < 0.01), followed by a decline (?0.08%, p = 0.08), returning to its pre-program increase rate. We noted a significant decrease in FOBT participation every summer (?0.44%, p < 0.01). The CCC program had minimal effect on large bowel endoscopy participation. Before the launch of the CCC program, the quarterly increase in ‘up-to-date’ with CRC screening was 0.9% (p < 0.01), increased immediately after the launch (2.5%, p = 0.05), followed by a modest decline thereafter (?0.59%, p < 0.02). From 2005 to 2011, recent residents living in low-income neighborhoods were consistently and significantly less likely to have a FOBT and be ‘up-to-date’ with CRC screening than long-term residents living in high-income neighborhoods (2.9–4.5%; 14.7–17.3% respectively). Pre-CCC inequities in CRC participation persisted after the launch of the program. Conclusion: CRC testing was increasing in Ontario from 2005. An immediate increase in CRC testing, FOBT in particular, occurred after the launch of the CCC program, followed by a return to its pre-CCC increase rate thereafter. Future efforts are needed to improve screening participation and address inequities.     

Community-based colorectal cancer intervention in underserved Korean Americans

Background: Despite evidence of a decline in both incidence and prevalence of colorectal cancer nationwide, it remains the second most commonly diagnosed cancer and the third highest cause of mortality among Asian Americans, including Korean Americans. This community-based and theoretically guided study evaluated a culturally appropriate intervention program that included a bilingual cancer educational program among Korean Americans including information on CRC risks, counseling to address psychosocial and access barriers, and patient navigation assistance. Methods: A two-group quasi-experimental design with baseline and post-intervention assessment and a 12-month follow-up on screening was used in the study. Korean Americans (N = 167) were enrolled from six Korean churches. The intervention group received culturally appropriate intervention program addressing accessibility and psychosocial barriers, and navigation assistance for screening. The control group received general health education that included cancer-related health issues and screening. Results: There was a significant difference (p < 0.05) between the post-intervention and control groups in awareness of CRC risk factors. There was also a significant improvement in the pre–post across HBM measures in the intervention group for perceived susceptibility (p < 0.05) and benefits and barriers to screening (p < 0.001). At baseline, 13% of participants in the intervention group and 10% in control group reported having had a CRC cancer screening test in the previous year. At the 12-month post-intervention follow-up, 77.4% of participants in the intervention group had obtained screening compared to 10.8% in the control group. Conclusion: While health disparities result from numerous factors, a culturally appropriate and church-based intervention can be highly effective in increasing knowledge of and access to, and in reducing barriers to CRC screening among underserved Koreans.     

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based,propensity score analysis

BackgroundThis study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis.MethodsData on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not.ResultsAfter adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR = 0.27, 95% CI: 0.20–0.38) lower risk of all-cause mortality and 72% (HR = 0.28, 95% CI: 0.20–0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR = 0.43, 95% CI: 0.31–0.59) and 54% (HR = 0.46, 95% CI: 0.33–0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis.ConclusionsThese findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.     

Germline HOXB13 p.Gly84Glu mutation and risk of colorectal cancer

Introduction: The HOXB13 pGly84Glu mutation has recently been associated with an increased risk of prostate cancer but the association of other cancer sites with this allele has not been assessed. Data has suggested that HOXB13 expression levels are decreased in colorectal cancer (CRC) cell lines indicating this gene may be involved in colorectal tumourigenesis. Methods: To evaluate a potential association of this mutation with CRC, we genotyped the mutation in 2695 CRC cases and 4593 controls from population-based registries in Canada and Australia. Results: The HOXB13 pGly84Glu mutation was more common in CRC cases than controls (0.48% vs. 0.17%, P = 0.02) indicating a significant association between the HOXB13 variant and CRC risk (OR = 2.8; 95%CI: 1.2–6.8). This association was attenuated but remained significant with the inclusion of previously published and publicly available genotype data. Pedigree analysis of cases and controls revealed that 7/21 HOXB13 mutation carriers had a family history of prostate cancer. Discussion: This report is the first to suggest a risk of CRC associated with mutations in the HOXB13 gene. These findings require further validation but may be of importance in the screening and genetic counseling of families known to carry the HOXB13 pGly84Glu mutation.     

Prediagnostic serum calcium and albumin and ovarian cancer: A nested case-control study in the Norwegian Janus Serum Bank Cohort

BackgroundWomen with higher serum calcium may be more likely to be diagnosed and die of ovarian cancer. We evaluated that finding in a large, prospective cohort.MethodsWe conducted a nested case-control study using a population-based biobank from Norway. We compared 202 ovarian cancer cases and 202 controls, matched for age, date at blood draw, and county of residence, with respect to serum calcium and albumin, adjusted for anthropometric variables. We evaluated risks using the entire follow-up period as well as 2–15 years and 16–25 years (“early” and “late”, respectively).ResultsFor the entire follow-up, risk was significantly increased in the highest tertile of albumin and for high albumin and calcium jointly. Risks for ovarian cancer differed markedly by follow-up time. In early follow-up, women in the highest tertile of serum calcium had a 2.5-fold increased risk, adjusted for height and body mass index (OR = 2.47, 95% C.I. 1.12–5.45) with a significant dose-response (p = 0.024). Risk was not elevated in late follow-up (OR = 0.62, 95% C.I. 0.27–1.36). Similarly, in early follow-up, women in the highest tertile of serum albumin had an increased risk (OR = 2.55, 95% C.I.1.22–5.49) with a significant dose-response (p = 0.009). Conversely, risk was not increased in late follow-up (OR = 1.36, 95% C.I. 0.65–2.83).ConclusionsThese data confirm a prospective association between higher serum calcium and ovarian cancer. An association in early, but not late, follow-up suggests that the higher calcium reflects the presence of existing cancer. A positive association with serum albumin is novel and should be interpreted cautiously.     

Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

ObjectivesZinc may play a role in the development of type 2 diabetes (T2D), because it is involved in antioxidant and anti-inflammatory activities. However, the role of zinc in the etiology of T2D has been poorly investigated. This study was conducted to study the association of serum zinc on T2D risk in middle-aged and older Finnish men.MethodsThis was a 20-year prospective follow-up study on 2220 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) who were 42 to 60 years old at baseline in 1984–1989. The main outcome was incident T2D. Serum zinc, body mass index (BMI), fasting blood glucose (FBG), serum insulin, C-reactive protein (CRP) and, in a subset of 751 participants, insulin-like growth factor-binding protein-1 (IGFBP-1), were measured. Also, the homeostatic model assessment (HOMA) was used to quantify insulin resistance (HOMA-IR), beta-cell function (HOMA-β) and insulin sensitivity (HOMA-IS).ResultsAt baseline, serum zinc was associated with higher BMI, serum insulin, HOMA-IR, HOMA-β and IGFBP-1 and lower HOMA-IS. During the average follow-up of 19.3 years, 416 men developed T2D. Men in the highest quartile of serum zinc had 60% higher risk (95% CI 20–113%; P-trend < 0.001) for incident T2D compared with the men in the lowest quartile, after multivariate adjustments. This association was attenuated after adjustment for BMI (HR = 1.39, 95% CI 1.04–1.85; P-trend = 0.013) or HOMA-IS (HR = 1.38, 95% CI 1.04–1.83; P-trend = 0.015), whereas adjustment for the other factors had only modest impact on the association.ConclusionHigher serum zinc was associated with higher risk of T2D; effects of zinc on BMI and insulin sensitivity may partly explain the association. Further prospective studies are warranted to confirm our results and explore potential mechanisms.