Waist Circumference Might Be a Predictor of Primary Liver Cancer: A Population-Based Cohort Study

Background: Waist circumference, as an indicator of central adiposity, has been identified as an important predictor of several specific cancers such as colorectal cancer and gastroesophageal cancer risk, however, a consensus regarding the association between waist circumference and primary liver cancer (PLC) risk has not been reached.Methods: A total of 104,825 males participating in the health checkup were included in the Kailuan male cohort study (2006–2015). Information on demographic and socioeconomic characteristics, lifestyle, medical records, and anthropometric measures were collected. Restricted cubic spline (RCS) and Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of association between waist circumference and the risk of PLC in males.Results: During a median of 8.9 years of follow-up, 346 PLC cases were newly diagnosed in the cohort. The RCS model showed a U-shaped association between waist circumference and PLC risk (P-overall = 0.019, P-non-linear = 0.017). Overally, males with both high waist circumference (HRQ5vs.Q3 = 1.98, 95%CI: 1.39–2.82) and low waist circumference (HRQ1vs.Q3 = 1.52, 95%CI: 1.02–2.27) had an increased risk of PLC. Especially, the U-shaped association between waist circumference and PLC risk tended to be strengthened among subjects with hepatitis B surface antigen (HBsAg) negativity (HRQ5vs.Q3 = 2.39, 95%CI: 1.43–3.98; HRQ1vs.Q3 = 2.27, 95%CI = 1.29–4.01).Conclusions: Waist circumference might be an independent predictor of PLC risk in males, especially for subjects with HBsAg negativity. Controlling waist circumference in an appropriate range might be an effective primary prevention to decrease PLC risk

The changes of subtype markers between first and second primary breast cancers

Abstract Background Previous studies investigated the changes of subtype markers [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)] in several clinical settings, but not for second primary breast cancer (SPBC) after first primary breast cancer (FPBC). Methods A total of 15,390 patients with SPBC were preliminarily selected from the Surveillance, Epidemiology, and End Results Program, and 3777 patients with complete information on three subtype markers in both FPBC and SPBC were included in the final analyses. The changes of subtype markers and their prognostic implications and potential influential factors were well investigated. Results The overall change rates of ER, PR, and HER2 between FPBC and SPBC were 23.0% (867/3777), 35.0% (1322/3777), and 18.3% (691/3777), respectively. Gains of ER, PR, and HER2 after negative index markers were 48.7% (364/748), 37.9% (418/1103), and 11.5% (370/3211), while losses of markers after positive index markers were 16.6% (503/3029), 33.8%(904/2674), and 56.7%(321/566). Loss of ER was significantly associated with increased mortality (18.1% vs. 7.9%, p < 0.001), while gain of ER was significantly associated with decreased mortality (11.5% vs. 23.2%, p < 0.001). Similar results were observed for changes of PR status. However, loss of HER2 was significantly associated with decreased mortality (8.7% vs. 16.3%, p = 0.014), and no significant association was observed between the gain of HER2 and the prognosis of SPBC. Multivariate competing risk analyses showed similar results. HER2 status in FPBC, chemotherapy, and radiotherapy was significantly associated with changes of ER/PR (all p < 0.05), and no available therapies associated with HER2 change. Conclusion The changes of subtype markers are observed in a considerable proportion of patients and has statistically significant prognostic implications. Biopsies should be taken as a routine procedure for better therapy management

Sleep duration and the risk of cancer: a systematic review and meta-analysis including dose–response relationship

Abstract Background The effect of sleep duration on cancer risk remains controversial. We aimed to quantify the available evidence on this relationship using categorical and dose–response meta-analyses. Methods Population-based cohort studies and case-control studies with at least three categories of sleep duration were identified by searching PubMed, EMBASE, and the Cochrane Library database up to July 2017. Results Sixty-five studies from 25 articles were included, involving 1,550,524 participants and 86,201 cancer cases. The categorical meta-analysis revealed that neither short nor long sleep duration was associated with increased cancer risk (short: odds ratio [OR] = 1.01, 95% confidence intervals [CI] = 0.97–1.05; long: OR = 1.02, 95% CI = 0.97–1.07). Subgroup analysis revealed that short sleep duration was associated with cancer risk among Asians (OR = 1.36; 95% CI: 1.02–1.80) and long sleep duration significantly increased the risk of colorectal cancer (OR = 1.21; 95% CI: 1.08–1.34). The dose–response meta-analysis showed no significant relationship between sleep duration and cancer risk. When treated as two linear piecewise functions with a cut point of 7 h, similar nonsignificant associations were found (per 1-h reduction: OR = 1.02, 95% CI = 0.98–1.07; per 1-h increment: OR = 1.003, 95% CI = 0.97–1.03). Conclusion Categorical meta-analysis indicated that short sleep duration increased cancer risk in Asians and long sleep duration increased the risk of colorectal cancer, but these findings were not consistent in the dose–response meta-analysis. Long-term randomized controlled trials and well-designed prospective studies are needed to establish causality and to elucidate the mechanism underlying the association between sleep duration and cancer risk

Human papillomavirus in semen and the risk for male infertility: a systematic review and meta-analysis

Abstract Background Human papillomavirus (HPV) is one of the most prevalent sexually transmitted viruses. Despite the increasing evidence of HPV prevalence in semen, the worldwide distribution of HPV types in semen and risk for male infertility remain inconclusive. Methods Four electronic databases were searched for English language studies conducted between January 1990 and December 2016 that reported HPV DNA prevalence in semen. Based on the PRISMA guidelines, HPV prevalence was estimated among general population and fertility clinic attendees, respectively, and heterogeneity testing was performed using Cochran’s Q and I 2 statistics. The association between HPV positivity and male infertility was evaluated by a meta-analysis of case-control studies. Results A total of 31 eligible studies comprising 5194 males were included. The overall prevalence of HPV DNA in semen was 11.4% (95% CI = 7.8-15.0%) in general population (n = 2122) and 20.4% (95% CI = 16.2-24.6%) in fertility clinic attendees (n = 3072). High-risk type prevalence was 10.0% (95% CI = 5.9-14.0%) and 15.5% (95% CI = 11.4-19.7%), respectively. HPV16 was the most common type, with a prevalence of 4.8% (95% CI = 1.7-7.8%) in general population and 6.0% (95% CI = 3.8-8.2%) in fertility clinic attendees. A significantly increased risk of infertility was found for males with HPV positivity in semen (OR = 2.93, 95% CI = 2.03-4.24). Conclusions Seminal HPV infection is common worldwide, which may contribute to the risk of male infertility

Risk-stratified multi-round PSA screening for prostate cancer integrating the screening reference level and subgroup-specific progression indicators

Abstract Background Although prostate-specific antigen (PSA) is widely used in prostate cancer (PCa) screening, nearly half of PCa cases are missed and less than one-third of cases are non-lethal. Adopting diagnostic criteria in population-based screening and ignoring PSA progression are presumed leading causes. Methods A total of 31,942 participants with multi-round PSA tests from the PLCO trial were included. Time-dependent receiver-operating-characteristic curves and area under curves (tdAUCs) were performed to determine the screening reference level and the optimal subgroup-specific progression indicator. Effects of risk-stratified multi-round PSA screening were evaluated with multivariable Cox regression and measured with hazard ratio [HR (95%CIs)]. Results After a median follow-up of 11.6 years, a total of 3484 PCa cases and 216 PCa deaths were documented. The tdAUC of 10-year incidence PCa with PSA was 0.816, and the cut-off value was 1.61 ng/ml. Compared to subgroup with stable negative PSA in both first-round (FR) and last-round (LR) tests [FR(−)/LR(−)], HRs (95%CI) of PCa incidence were 1.66 (1.20–2.29), 8.29 (7.25–9.48), and 14.52 (12.95–16.28) for subgroups with loss of positive PSA[FR(+)/LR(−)], gain of positive PSA[FR(−)/LR(+)], and stable positive PSA[FR(+)/LR(+)]; while HRs(95%CI) of PCa mortality were 1.47 (0.52–4.15), 5.71 (3.68–8.86), and 5.01 (3.41–7.37). After excluding regressive PSA [(namely FR(+)/LR(−)], absolute velocity was the shared optimal progression indicator for subgroups with FR(−)/LR(−), FR(−)/LR(+), and FR(+)/LR(+), with tdAUCs of 0.665, 0.681 and 0.741, and cut-off values of 0.07, 0.21, and 0.33 ng/ml/year. After reclassifying participants into groups with positive and negative progression based on subgroup-specific progression indicators, incidence HR (95%CI) were 2.41 (1.87–3.10), 2.91 (2.43–3.48), and 3.16 (2.88–3.46) for positive progression compared to negative progression within subgroups of FR(−)/LR(−), FR(−)/LR(+), and FR(+)/LR(+), while mortality HR (95%CI) were 2.22 (0.91–5.38), 2.37 (1.28–4.38), and 2.98 (1.94–4.59). To improve screening performances by excluding regressive PSA and low-risk positive progression in FR(−)/LR(−), optimized screening strategy not only significantly reduce 32.4% of missed PCa (54.0% [1881/3484] vs. 21.6% [754/3484], P < 0.001), but also detected additional 8.0% of high-grade PCa (Gleason score 7–10: 36.0% [665/1849] vs. 28.0% [206/736], P < 0.001) than traditional screening strategy. Conclusions Risk-stratified multi-round PSA screening strategy integrating the screening reference level and the optimal subgroup-specific progression indicator of PSA could be recommended as a fundamental strategy to reduce missed diagnosis and improve the detection of high-grade PCa cases

Independent prognostic role of human papillomavirus genotype in cervical cancer

Abstract Background Although the correlation of HPV genotype with cervical precursor lesions and invasive cancer has been confirmed, the role of HPV genotype in cervical cancer prognosis is less conclusive. This study aims to systematically investigate the independent prognostic role of HPV genotype in cervical cancer. Methods A total of 306 eligible patients provided cervical cell specimens for HPV genotyping before therapy and had a median follow-up time of 54 months after diagnosis. Survival times were measured from the date of diagnosis to the date of cervical cancer-related death (overall survival, OS) and from the date of diagnosis to the date of recurrence or metastasis (disease free survival, DFS). Log-rank tests and Cox proportional hazard models were performed to evaluate the association between HPV genotype and survival times. Results A total of 12 types of high-risk HPV were detected and the leading ten types belong to two species: alpha-9 and alpha-7. HPV16 and 18 were the two most common types, with the prevalence of 60.8% and 8.8%, respectively. In the univariate analysis, HPV16-positive cases were associated with better OS (P = 0.037) and HPV16-related species alpha-9 predicted better OS and DFS (both P < 0.01). After adjusting for age, FIGO stage, and therapy, HPV16 showed a hazard ratio (HR) of 0.36 (95% CI: 0.18, 0.74; P = 0.005) for OS, and alpha-9 resulted in a HR of 0.17 (95% CI: 0.08, 0.37; P < 0.001) for OS and 0.32 (95% CI: 0.17, 0.59; P < 0.001) for DFS. Conclusions HPV genotype poses differential prognoses for cervical cancer patients. The presence of HPV16 and its related species alpha-9 indicates an improved survival

DataSheet_1_Effects of joint screening for prostate, lung, colorectal, and ovarian cancer – results from a controlled trial.docx

BackgroundAlthough screening is widely used to reduce cancer burden, untargeted cancers are frequently missed after single cancer screening. Joint cancer screening is presumed as a more effective strategy to reduce overall cancer burden.MethodsGender-specific screening effects on PLCO cancer incidence, PLCO cancer mortality, all-neoplasms mortality and all-cause mortality were evaluated, and meta-analyses based on gender-specific screening effects were conducted to achieve the pooled effects. The cut-off value of time-dependent receiver-operating-characteristic curve of 10-year combined PLCO cancer risk was used to reclassify participants into low- and high-risk subgroups. Further analyses were conducted to investigate screening effects stratified by risk groups and screening compliance.ResultsAfter a median follow-up of 10.48 years for incidence and 16.85 years for mortality, a total of 5,506 PLCO cancer cases, 1,845 PLCO cancer deaths, 3,970 all-neoplasms deaths, and 14,221 all-cause deaths were documented in the screening arm, while 6,261, 2,417, 5,091, and 18,516 outcome-specific events in the control arm. Joint cancer screening did not significantly reduce PLCO cancer incidence, but significantly reduced male-specific PLCO cancer mortality (hazard ratio and 95% confidence intervals [HR(95%CIs)]: 0.88(0.82, 0.95)) and pooled mortality [0.89(0.84, 0.95)]. More importantly, joint cancer screening significantly reduced both gender-specific all-neoplasm mortality [0.91(0.86, 0.96) for males, 0.91(0.85, 0.98) for females, and 0.91(0.87, 0.95) for meta-analyses] and all-cause mortality [0.90(0.88, 0.93) for male, 0.88(0.85, 0.92) for female, and 0.89(0.87, 0.91) for meta-analyses]. Further analyses showed decreased risks of all-neoplasm mortality was observed with good compliance [0.72(0.67, 0.77) for male and 0.72(0.65, 0.80) for female] and increased risks with poor compliance [1.61(1.40, 1.85) for male and 1.30(1.13, 1.40) for female].ConclusionJoint cancer screening could be recommended as a potentially strategy to reduce the overall cancer burden. More compliance, more benefits. However, organizing a joint cancer screening not only requires more ingenious design, but also needs more attentions to the potential harms.Trial registrationNCT00002540 (Prostate), NCT01696968 (Lung), NCT01696981 (Colorectal), NCT01696994 (Ovarian).</p

Additional file 1: Table S1. of Independent prognostic role of human papillomavirus genotype in cervical cancer

Multiple HPV infections in cervical cancer patients. This table is the supporting information for line 169–171. Table S2. Survival analysis of the alpha-9 types in cervical cancer patients. This table is the supporting information for line 193–196. Table S3. Stratified analysis of HPV genotype and cervical cancer survival. This table is the supporting information for line 198–203. (DOCX 40 kb