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Background High-throughput profiling of DNA methylation status of CpG islands is crucial to understand the epigenetic regulation of genes. The microarray-based Infinium methylation assay by Illumina is one platform for low-cost high-throughput methylation profiling. Both Beta-value and M-value statistics have been used as metrics to measure methylation levels. However, there are no detailed studies of their relations and their strengths and limitations. Results We demonstrate that the relationship between the Beta-value and M-value methods is a Logit transformation, and show that the Beta-value method has severe heteroscedasticity for highly methylated or unmethylated CpG sites. In order to evaluate the performance of the Beta-value and M-value methods for identifying differentially methylated CpG sites, we designed a methylation titration experiment. The evaluation results show that the M-value method provides much better performance in terms of Detection Rate (DR) and True Positive Rate (TPR) for both highly methylated and unmethylated CpG sites. Imposing a minimum threshold of difference can improve the performance of the M-value method but not the Beta-value method. We also provide guidance for how to select the threshold of methylation differences. Conclusions The Beta-value has a more intuitive biological interpretation, but the M-value is more statistically valid for the differential analysis of methylation levels. Therefore, we recommend using the M-value method for conducting differential methylation analysis and including the Beta-value statistics when reporting the results to investigators.

Mediation analysis plays a major role in identifying significant mediators in the pathway between environmental exposures and health outcomes. With advanced data collection technology for large-scale studies, there has been growing research interest in developing methodology for high-dimensional mediation analysis. In this paper we present HIMA2, an extension of the HIMA method (Zhang in Bioinformatics 32:3150–3154, 2016). First, the proposed HIMA2 reduces the dimension of mediators to a manageable level based on the sure independence screening (SIS) method (Fan in J R Stat Soc Ser B 70:849–911, 2008). Second, a de-biased Lasso procedure is implemented for estimating regression parameters. Third, we use a multiple-testing procedure to accurately control the false discovery rate (FDR) when testing high-dimensional mediation hypotheses. We demonstrate its practical performance using Monte Carlo simulation studies and apply our method to identify DNA methylation markers which mediate the pathway from smoking to reduced lung function in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

The aim of the present study was to evaluate the single and joint associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Tianjin, China. Between June 2009 and May 2011, health care records of 33,973 pregnant women were collected and their children were measured for birth weight and birth length. The independent and joint associations of prepregnancy BMI and GWG based on the Institute of Medicine (IOM) guidelines with the risks of pregnancy and neonatal outcomes were examined by using Logistic Regression. After adjustment for all confounding factors, maternal prepregnancy BMI was positively associated with risks of gestational diabetes mellitus (GDM), pregnancy-induced hypertension, caesarean delivery, preterm delivery, large-for-gestational age infant (LGA), and macrosomia, and inversely associated with risks of small-for-gestational age infant (SGA) and low birth weight. Maternal excessive GWG was associated with increased risks of pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia, and decreased risks of preterm delivery, SGA, and low birth weight. Maternal inadequate GWG was associated with increased risks of preterm delivery and SGA, and decreased risks of LGA and macrosomia, compared with maternal adequate GWG. Women with both prepregnancy obesity and excessive GWG had 2.2-5.9 folds higher risks of GDM, pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia compared with women with normal prepregnancy BMI and adequate GWG. Maternal prepregnancy obesity and excessive GWG were associated with greater risks of pregnancy-induced hypertension, caesarean delivery, and greater infant size at birth. Health care providers should inform women to start the pregnancy with a BMI in the normal weight category and limit their GWG to the range specified for their prepregnancy BMI.

Although cervical cancer is largely preventable through screening, detection and treatment of precancerous abnormalities, it remains one of the top causes of cancer-related morbidity and mortality globally. The objective of this systematic review is to understand the evidence of the effect of cervical cancer education compared to control conditions on cervical cancer screening rates in eligible women population at risk of cervical cancer. We also sought to understand the effect of provider recommendations for screening to eligible women on cervical cancer screening (CCS) rates compared to control conditions in eligible women population at risk of cervical cancer. We used the PICO (Problem or Population, Interventions, Comparison and Outcome) framework as described in the Cochrane Collaboration Handbook to develop our search strategy. The details of our search strategy has been described in our systematic review protocol published in the International Prospective Register of systematic reviews (PROSPERO). The protocol registration number is CRD42016045605 available at: http://www.crd.york.ac.uk/prospero/display_record.asp?src=trip&ID=CRD42016045605. The search string was used in Pubmed, Embase, Cochrane Systematic Reviews and Cochrane CENTRAL register of controlled trials to retrieve study reports that were screened for inclusion in this review. Our data synthesis and reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). We did a qualitative synthesis of evidence and, where appropriate, individual study effects were pooled in meta-analyses using RevMan 5.3 Review Manager. The Higgins I2 was used to assess for heterogeneity in studies pooled together for overall summary effects. We did assessment of risk of bias of individual studies included and assessed risk of publication bias across studies pooled together in meta-analysis by Funnel plot. Out of 3072 study reports screened, 28 articles were found to be eligible for inclusion in qualitative synthesis (5 of which were included in meta-analysis of educational interventions and 8 combined in meta-analysis of HPV self-sampling interventions), while 45 were excluded for various reasons. The use of theory-based educational interventions significantly increased CCS rates by more than double (OR, 2.46, 95% CI: 1.88, 3.21). Additionally, offering women the option of self-sampling for Human Papillomavirus (HPV) testing increased CCS rates by nearly 2-fold (OR = 1.71, 95% CI: 1.32, 2.22). We also found that invitation letters alone (or with a follow up phone contact), making an appointment, and sending reminders to patients who are due or overdue for screening had a significant effect on improving participation and CCS rates in populations at risk. Our findings supports the implementation of theory-based cervical cancer educational interventions to increase women's participation in cervical cancer screening programs, particularly when targeting communities with low literacy levels. Additionally, cervical cancer screening programs should consider the option of offering women the opportunity for self-sample collection particularly when such women have not responded to previous screening invitation or reminder letters for Pap smear collection as a method of screening.

Purpose Circulating tumor cell (CTC) is a well-established prognosis predictor for metastatic breast cancer (MBC), and CTC-cluster exhibits significantly higher metastasis-promoting capability than individual CTCs. Because measurement of CTCs and CTC-clusters at a single time point may underestimate their prognostic values, we aimed to analyze longitudinally collected CTCs and CTC-clusters in MBC prognostication. Methods CTCs and CTC-clusters were enumerated in 370 longitudinally collected blood samples from 128 MBC patients. The associations between baseline, first follow-up, and longitudinal enumerations of CTCs and CTC-clusters with patient progression-free survival (PFS) and overall survival (OS) were analyzed using Cox proportional hazards models. Results CTC and CTC-cluster counts at both baseline and first follow-up were significantly associated with patient PFS and OS. Time-dependent analysis of longitudinally collected samples confirmed the significantly unfavorable PFS and OS in patients with ≥5 CTCs, and further demonstrated the independent prognostic values by CTC-clusters compared to CTC-enumeration alone. Longitudinal analyses also identified a link between the size of CTC-clusters and patient OS: compared to the patients without any CTC, those with 2-cell CTC-clusters and ≥3-cell CTC-clusters had a hazard ratio (HR) of 7.96 [95 % confidence level (CI) 2.00–31.61, P  = 0.003] and 14.50 (3.98–52.80, P  < 0.001), respectively. Conclusions In this novel time-dependent analysis of longitudinally collected CTCs and CTC-clusters, we showed that CTC-clusters added additional prognostic values to CTC enumeration alone, and a larger-size CTC-cluster conferred a higher risk of death in MBC patients.

Unprotected oral sex is associated with sexually transmitted infections (STIs) including HPV and associated head and neck cancers. However, many studies lack clear definitions of oral sex and there are few data from West Africa. This study assessed the pattern and prevalence of, and factors associated with oral sex among Nigerian men and women from the general population. The Sexual Behaviours and HPV Infections in Nigerians in Ibadan (SHINI) study was a cross-sectional study conducted among men and women aged 18-45 years. Information on oral sexual behaviours was collected during a face-to-face interview by a sex-matched interviewer. Descriptive and multivariable analyses were used to analyse factors associated with oral sex in men and women. In total, 160/626 (26%) had ever any type of oral sex. Specifically, 78/626 (12%) had ever given and 139/626 (22%) had ever received oral sex in a heterosexual relationship. Overall, 35% (112/310) men had ever engaged in oral sex compared to women 15% (48/316 -p < 0.001). More men frequently reported ever receiving oral sex than women (33% vs. 12%; p < 0.001). There was no difference in the proportion of men and women that reported ever giving oral sex. Most (94%) participants never used any barrier protection during oral sex. Most men and women participants engaged in oral sex because of romantic relationship or being married. In the adjusted models, there was a higher odds of ever receiving oral sex (Adjusted odds ratio = AOR 4.01 95% CI 2.52-6.38) or engaging in any form of oral sex (AOR = 3.12, 95%CI 2.04-4.76) in men than women. Though, Nigerian men and women engage in oral sex in heterosexual relationship, but it is more commonly reported by men than women and most of them practiced it without barrier protection. It is recommended that sexually active men and women are counselled on risks associated with unprotected oral sex including STIs, HIV and HPV and associated cancers.

Unprotected oral sex is associated with sexually transmitted infections (STIs) including HPV and associated head and neck cancers. However, many studies lack clear definitions of oral sex and there are few data from West Africa. This study assessed the pattern and prevalence of, and factors associated with oral sex among Nigerian men and women from the general population. The Sexual Behaviours and HPV Infections in Nigerians in Ibadan (SHINI) study was a cross-sectional study conducted among men and women aged 18-45 years. Information on oral sexual behaviours was collected during a face-to-face interview by a sex-matched interviewer. Descriptive and multivariable analyses were used to analyse factors associated with oral sex in men and women. In total, 160/626 (26%) had ever any type of oral sex. Specifically, 78/626 (12%) had ever given and 139/626 (22%) had ever received oral sex in a heterosexual relationship. Overall, 35% (112/310) men had ever engaged in oral sex compared to women 15% (48/316 -p < 0.001). More men frequently reported ever receiving oral sex than women (33% vs. 12%; p < 0.001). There was no difference in the proportion of men and women that reported ever giving oral sex. Most (94%) participants never used any barrier protection during oral sex. Most men and women participants engaged in oral sex because of romantic relationship or being married. In the adjusted models, there was a higher odds of ever receiving oral sex (Adjusted odds ratio = AOR 4.01 95% CI 2.52-6.38) or engaging in any form of oral sex (AOR = 3.12, 95%CI 2.04-4.76) in men than women. Though, Nigerian men and women engage in oral sex in heterosexual relationship, but it is more commonly reported by men than women and most of them practiced it without barrier protection. It is recommended that sexually active men and women are counselled on risks associated with unprotected oral sex including STIs, HIV and HPV and associated cancers.

Purpose: Inflammation is a process central to carcinogenesis and in particular to colorectal cancer (CRC). Previously, we developed a dietary inflammatory index (DII) from extensive literature review to assess the inflammatory potential of diet. In the current study, we utilized this novel index in the Women's Health Initiative to prospectively evaluate its association with risk of CRC in postmenopausal women. Methods: The DII was calculated from baseline food frequency questionnaires administered to 152,536 women aged 50–79 years without CRC at baseline between 1993 and 1998 and followed through 30 September 2010. Incident CRC cases were ascertained through a central physician adjudication process. Multiple covariate-adjusted Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) for colorectal, colon (proximal/distal locations), and rectal cancer risk, by DII quintiles (Q). Results: During an average 11.3 years of follow-up, a total of 1,920 cases of CRC (1,559 colon and 361 rectal) were identified. Higher DII scores (representing a more pro-inflammatory diet) were associated with an increased incidence of CRC (HRQ5-Q1 1.22; 95 % CI 1.05, 1.43; Ptrend = 0.02) and colon cancer, specifically proximal colon cancer (HRQ5-Q1 1.35; 95 % CI 1.05, 1.67; Ptrend 0.01) but not distal colon cancer (HRQ5-Q1 0.84; 95 % CI 0.61, 1.18; Ptrend = 0.63) or rectal cancer (HRQ5-Q1 1.20; 95 % CI 0.84, 1.72; Ptrend = 0.65). Conclusion: Consumption of pro-inflammatory diets is associated with an increased risk of CRC, especially cancers located in the proximal colon. The absence of a significant association for distal colon cancer and rectal cancer may be due to the small number of incident cases for these sites. Interventions that may reduce the inflammatory potential of the diet are warranted to test our findings, thus providing more information for colon cancer prevention.

This study aimed to identify and quantify the relative and collective contributions of lifestyle, behavioral, and biological risk factors to cervical HPV infections among female sex workers (FSWs) in Ibadan, Nigeria. This cross-sectional study was part of the Sexual Behavior and HPV Infections in Nigerians in Ibadan project and involved 182 FSWs for whom complete data on HPV genotypes were available. Quantile-based g-computation was employed to assess the relative and collective contributions of risk factors to any cervical HPV/hrHPV infections and multiple cervical HPV/hrHPV. The collective contribution of all selected risk factors to multiple high-risk cervical HPV was 2.47 (95% CI: 0.97–3.23). The number of other anatomic sites with HPV infections showed the highest positive relative contribution to multiple cervical HPV/hrHPV. Alcohol consumption and the total number of sexual partners contributed to high-risk cervical HPV and multiple cervical HPV/hrHPV, while age at first vaginal sex had a negative relative contribution. This study highlights the significant contribution of HPV infections in multiple anatomic sites as a risk to the acquisition of cervical HPV in FSWs. Routine screening protocols should be enhanced to include multiple anatomic sites, and targeted educational programs are recommended to address the specific risks faced by FSWs.

Background: Diet modulates inflammation and inflammatory markers have been associated with cancer outcomes. In the Women’s Health Initiative, we investigated associations between a dietary inflammatory index (DII) and invasive breast cancer incidence and death. Methods: The DII was calculated from a baseline food frequency questionnaire in 122 788 postmenopausal women, enrolled from 1993 to 1998 with no prior cancer, and followed until 29 August 2014. With median follow-up of 16.02 years, there were 7495 breast cancer cases and 667 breast cancer deaths. We used Cox regression to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (95% CIs) by DII quintiles (Q) for incidence of overall breast cancer, breast cancer subtypes, and deaths from breast cancer. The lowest quintile (representing the most anti-inflammatory diet) was the reference. Results: The DII was not associated with incidence of overall breast cancer (HR Q5 vs Q1 , 0.99; 95% CI, 0.91–1.07; P trend =0.83 for overall breast cancer). In a full cohort analysis, a higher risk of death from breast cancer was associated with consumption of more pro-inflammatory diets at baseline, after controlling for multiple potential confounders (HR Q5 vs Q1 , 1.33; 95% CI, 1.01–1.76; P trend =0.03). Conclusions: Future studies are needed to examine the inflammatory potential of post-diagnosis diet given the suggestion from the current study that dietary inflammatory potential before diagnosis is related to breast cancer death.