Men are at higher risk of developing chronic lymphocytic leukemia (CLL) than women. DNA methylation has been shown to play important roles in a number of cancers. There are differences in the DNA methylation pattern between men and women. In this study, we investigated whether this contributes to the sex-related difference of B cell CLL risk. Using the HumanMethylation450 BeadChip, we profiled the genome-wide DNA methylation pattern of CD19+ B cells from 48 CLL patients (29 female patients and 19 male patients) and 28 healthy people (19 women and 9 men). We identified 1043 sex-related differentially methylated positions (DMPs) related to CLL, 56 of which are located on autosomes and 987 on the X chromosome. Using published B cell RNA-sequencing data, we found 18 genes covered by the DMPs also have different expression levels in male and female CLL patients. Among them, TRIB1, an autosome gene, has been shown to promote tumor growth by suppressing apoptosis. Our study represents the first epigenome-wide association study (EWAS) that investigates the sex-related differences in cancer, and indicated that DNA methylation differences might contribute to the sex-related difference in CLL risk.

Since body fatness is a convincing risk factor for endometrial cancer, dietary fat intake was speculated to be associated with endometrial cancer risk. However, epidemiological studies are inconclusive. We aimed to conduct a meta-analysis to assess the associations between dietary fat intake and endometrial cancer risk. We searched the PubMed, Embase, and Web of science databases updated to September 2015. In total, 7 cohort and 14 case-control studies were included. Pooled analysis of case-control studies suggested that endometrial cancer risk was significantly increased by 5% per 10% kilocalories from total fat intake (P=0.02) and by 17% per 10 g/1000 kcal of saturated fat intake (P < 0.001). Summary of 3 cohort studies showed significant inverse association between monounsaturated fatty acids and endometrial cancer risk (odds ratio = 0.84, 95% confidence interval = 0.73-0.98) with a total of 524583 participants and 3503 incident cases. No significant associations were found for polyunsaturated fatty acids and linoleic acid. In conclusion, positive associations with endometrial cancer risk were observed for total fat and saturated fat intake in the case-control studies. Results from the cohort studies suggested higher monounsaturated fatty acids intake was significantly associated with lower endometrial cancer risk.

Oral isoflavone supplementation on endometrial thickness: a meta-analysis of randomized placebo-controlled trials

Arachidonic acid (AA) is the major polyunsaturated fatty acid (PUFA) substrate for potent eicosanoid signaling to modulate inflammation and thrombosis and is controlled in part by tissue abundance. Fatty acid desaturase 1 (FADS1) catalyzes synthesis of omega-6 (n-3) AA and n-3 eicosapentaenoic acid (EPA). The rs66698963 polymorphism, a 22-base pair (bp) insertion-deletion 137 bp downstream of a sterol regulatory element in FADS2 intron 1, mediates expression of FADS1 in vitro, as well as exerting positive selection in several human populations. The associations between the polymorphism rs66698963 and plasma PUFAs as well as disease phenotypes are unclear. This study aimed to evaluate the relation between rs66698963 genotypes and plasma PUFA concentrations and blood lipid profiles. Plasma fatty acids were measured from a single sample obtained at baseline in 1504 healthy Chinese adults aged between 35 and 59 y with the use of gas chromatography. Blood lipids were measured at baseline and a second time at the 18-mo follow-up. The rs66698963 genotype was determined by using agarose gel electrophoresis. Linear regression and logistic regression analyses were performed to assess the association between genotype and plasma PUFAs and blood lipids. A shift from the precursors linoleic acid and α-linolenic acid to produce AA and EPA, respectively, was observed, consistent with FADS1 activity increasing in the order of genotypes D/D to I/D to I/I. For I/I compared with D/D carriers, plasma concentrations of n-6 AA and the ratio of AA to n-3 EPA plus docosahexaenoic acid (DHA) were 57% and 32% higher, respectively. Carriers of the deletion (D) allele of rs66698963 tended to have higher triglycerides (β = 0.018; SE: 0.009; P = 0.05) and lower HDL cholesterol (β = -0.008; SE: 0.004; P = 0.02) than carriers of the insertion (I) allele. The rs66698963 genotype is significantly associated with AA concentrations and AA to EPA+DHA ratio, reflecting basal risk of inflammatory and related chronic disease phenotypes, and is correlated with the risk of dyslipidemia. This trial was registered at chictr.org.cn as ChiCTR-EOC-17012759.

Epidemiological studies are inconclusive regarding the association between dietary fiber intake and endometrial cancer risk. Thus, we aimed to conduct a meta-analysis to clarify the association between dietary fiber and endometrial cancer risk. We searched the PubMed and ISI Web databases for relevant studies through March 2018. The association between dietary fiber and endometrial cancer risk was evaluated by conducting a meta-analysis including 3 cohort and 12 case–control studies. A significant negative association was observed between total dietary fiber intake and endometrial cancer risk in 11 case–control studies (odds ratios (OR) 0.76, 95% confidence interval (CI): 0.64–0.89, I² = 35.2%, p = 0.117), but a marginal positive association was observed in three cohort studies (relative risk (RR) 1.22, 95% CI: 1.00–1.49, I² = 0.0%, p = 0.995). Particularly, a negative association was observed in North America (OR = 0.70, 95% CI: 0.59–0.83, I² = 8.9%, p = 0.362). In addition, a positive association was observed in cereal fiber (RR = 1.26, 95% CI: 1.03–1.52, I² = 0.0%, p = 0.530, 3 cohort studies) and a negative association was observed in vegetable fiber (OR = 0.74, 95% CI: 0.58–0.94, I² = 0.0%, p = 0.445, 3 case–control studies). In conclusion, negative associations with endometrial cancer risk were observed for higher total dietary fiber intake and higher vegetable fiber intake in the case–control studies. However, results from the cohort studies suggested positive relationships of higher total fiber intake and higher cereal fiber intake with endometrial cancer risk.