Dietary glycemic load, glycemic index, and carbohydrates on the risk of primary liver cancer among Chinese women and men.

BACKGROUND: Dietary glycemic index (GI) and glycemic load (GL) typically have a positive relationship with obesity and diabetes, which are risk factors for liver cancer. However, studies on their association with liver cancer have yielded inconsistent results. Therefore, we assessed the association of GI, GL, and carbohydrates with liver cancer risk. PATIENTS AND METHODS: A total of 72 966 women and 60 207 men from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) were included for analysis. Food frequency questionnaire (FFQ) data were used to calculate daily dietary GI, GL, and carbohydrate intake. These values were energy adjusted and categorized into quintiles. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated with adjustment for potential confounders. RESULTS: After a median follow-up time of 11.2 years for the SWHS and 5.3 years for the SMHS, 139 and 208 incident liver cancer cases were identified in the SWHS and SMHS, respectively. In multivariable Cox regression models, no statistically significant trends by quintile of GI, GL, or carbohydrate intake were observed. Stratification by chronic liver disease/hepatitis, diabetes, or body mass index (BMI) did not alter the findings. CONCLUSIONS: There is little evidence that dietary GI, GL, or carbohydrates affect the incidence of liver cancer in this Asian population.

Prospective evaluation of type 2 diabetes mellitus on the risk of primary liver cancer in Chinese men and women.

BACKGROUND: No prospective study has investigated the relationship between type 2 diabetes mellitus (T2DM) and the risk of primary liver cancer (PLC) in mainland China, and little is known about the effect of diabetes duration on PLC risk. DESIGN: Data from two population-based cohorts (the Shanghai Men's Health Study, SMHS, 2002-2006 and the Shanghai Women's Health Study, SWHS, 1996-2000) were thus used to assess the associations among T2DM, diabetes duration and PLC risk in Chinese population. RESULTS: During follow-up through 2009, 344 incident PLC cases were identified among 60 183 men and 73 105 women. T2DM is significantly associated with the increased risk of PLC in both men [hazard ratio (HR) = 1.63, 95% confidence interval (CI) 1.06-2.51] and women (HR = 1.64, 95% CI 1.03-2.61). The highest risk of incident liver cancer was observed in the first 5 years after diabetes diagnosis, and decreased substantially with the prolonged diabetes duration (P(trend) < 0.001). No synergistic interaction in the development of PLC was found between diabetes and other known risk factors. CONCLUSIONS: T2DM is associated with the increased risk of subsequent liver cancer within 5 years after diagnosis in Chinese population, suggesting that hyperinsulinaemia rather than hyperglycaemia is more likely to be a primary mediator for this association.

Cruciferous vegetables consumption and the risk of female lung cancer: a prospective study and a meta-analysis.

BACKGROUND: Epidemiological studies evaluating the association between cruciferous vegetables (CVs) intake and female lung cancer risk have produced inconsistent results. PATIENTS AND METHODS: This study followed 74 914 Chinese women aged 40-70 years who participated in the Shanghai Women's Health Study. CV intake was assessed through a validated food-frequency questionnaire (FFQ) at baseline and reassessed during follow-up. Hazard ratios (HRs) and 95% confidence interval (CIs) were estimated by using Cox proportional hazards models. Furthermore, we carried out a meta-analysis of all observational studies until December 2011. RESULTS: After excluding the first 2 years of follow-up, 417 women developed lung cancer over a mean of 11.1 years of follow-up. An inverse association of borderline statistical significance was observed between CV consumption and female lung cancer risk, with HR for the highest compared with the lowest quartiles of 0.73 (95% CI 0.54-1.00, P trend = 0.1607). The association was strengthened in analyses restricting to never smokers, with the corresponding HR of 0.59 (95% CI 0.40-0.87, P trend = 0.0510). The finding of an inverse association between CV intake and lung cancer risk in women was supported by our meta-analysis of 10 included studies. CONCLUSIONS: Our study suggests that CV consumption may reduce the risk of lung cancer in women, particularly among never smokers.

Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women.

STUDY QUESTION: Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry? SUMMARY ANSWER: Many genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Prior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to demonstrate that many of the genetic determinants of age at menarche are shared between European and Chinese women. PARTICIPANTS AND SETTING: We evaluated 37 of 42 SNPs identified as associated with age at menarche from a recent, large meta-analysis, consisting primarily of women of European ancestry, in a population of 6929 Chinese women from Shanghai, China. We also constructed weighted genetic risk scores (GRSs) combining the number of effect variants for all 37 SNPs, or only the SNPs associated with age at menarche among our study population, to evaluate their joint influence on age at menarche. MAIN RESULTS: For 32 of the 37 evaluated variants, the direction of the allele associations were the same between women of European ancestry and women of Chinese ancestry (P = 3.71 × 10(-6), binomial sign test); 9 of these were statistically significant. Subjects in the highest quintile of GRSs began menarche ∼5 months later than those in the lowest quintile. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: Age at menarche was obtained by self-report, which can be subject to recall errors. The current analysis was restricted to loci which met or approached GWAS significance thresholds and did not evaluate loci which may act predominantly or exclusively in the Chinese population. The smaller sample size for our meta-analysis compared with meta-analyses conducted in European populations reduced the power to detect significant results. STUDY FUNDING/COMPETING INTERESTS: This study was supported, in part, by grants from US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585 and UL1 RR024975), Ingram professorship funds and Allen Foundation funds. There are no competing interests to declare.

Blood leukocyte Alu and LINE-1 methylation and gastric cancer risk in the Shanghai Women's Health Study.

BACKGROUND: Recent data suggest a link between blood leukocyte DNA methylation, and cancer risk. However, reports on DNA methylation from a prospective study are unavailable for gastric cancer. METHODS: We explored the association between methylation in pre-diagnostic blood leukocyte DNA and gastric cancer risk in a case-control study nested in the prospective Shanghai Women's Health Study cohort. Incident gastric cancer cases (n=192) and matched controls (n=384) were included in the study. Methylation of Alu and long interspersed nucleotide elements (LINE)-1 were evaluated using bisulphite pyrosequencing. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders. RESULTS: Alu methylation was inversely associated with gastric cancer risk, mainly among cases diagnosed one or more years after blood collection. After excluding cases diagnosed during the first year of follow-up, the ORs for the third, second, and first quartiles of Alu methylation compared with the highest quartile were 2.43 (1.43-4.13), 1.47(0.85-2.57), and 2.22 (1.28-3.84), respectively. This association appeared to be modified by dietary intake, particularly isoflavone. In contrast, LINE-1 methylation levels were not associated with gastric cancer risk. CONCLUSION: Evidence from this prospective study is consistent with the hypothesis that DNA hypomethylation in blood leukocytes may be related to cancer risk, including risk of gastric cancer.

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).

BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

Physical activity and breast cancer risk in Chinese women.

BACKGROUND: The influence of different types and intensities of physical activity on risk for breast cancer is unclear. METHODS: In a prospective cohort of 73,049 Chinese women (40-70 years), who had worked outside the home, we studied breast cancer risk in relation to specific types of self-reported and work history-related physical activity, including adolescent and adult exercise and household activity and walking and cycling for transportation. Occupational sitting time and physical activity energy expenditure were assigned based on lifetime occupational histories. RESULTS: In all, 717 incident breast cancer cases were diagnosed. Breast cancer risk was lower for women in the lowest quartile of average occupational sitting time and in the highest quartile of average occupational energy expenditure (adjusted hazard ratio (HR): 0.81 and 0.73, respectively, P ≤ 0.05). Adult exercise at or above the recommended level (8 metabolic equivalent (MET) h per week per year) was associated with lower risk (adjusted HR: 0.73, P<0.05) in post-menopausal women. Analysis of joint effects showed that having both an active job and exercise participation did not confer an additional benefit. Other common daily activities were not associated with lower risk. INTERPRETATION: These findings suggest that both exercise and occupational activity are associated with lower breast cancer risk, which supports current health promotion campaigns promoting exercise.

Plasma pepsinogens, antibodies against Helicobacter pylori, and risk of gastric cancer in the Shanghai Women's Health Study Cohort.

BACKGROUND: Circulating pepsinogens can indicate atrophic gastritis, a precursor of gastric cancer. We tested the association between gastric cancer and plasma pepsinogens and antibodies against Helicobacter pylori in a case-control study nested in a prospective cohort. METHODS: We selected 141 gastric cancer cases and 282 incidence-density sampled controls. Plasma concentrations of pepsinogens 1 and 2 were measured using ELISA kits, and anti-H. pylori antibodies were measured using a kit specific to Chinese strains. Associations were estimated using conditional logistic regression models adjusted for potential confounders. RESULTS: Gastric cancer subjects were more likely to be anti-H. pylori positive than controls, 97 vs 92%. A plasma pepsinogen 1 (PG1) concentration <50 ng ml(-1) (15% of cases) was associated with a significantly increased risk of gastric cancer (OR 4.23; (95% CI: 1.86-9.63), whereas a plasma pepsinogen 2 (PG2) concentration >6.6 ng ml(-1) (75% of cases) was also associated with a significantly increased risk of gastric cancer (OR 3.62; (95% CI: 1.85-7.09). We also found that the PG1 : 2 ratio had a nearly linear association with gastric cancer risk. CONCLUSION: Lower plasma PG1 : 2 ratios are associated with a higher risk of gastric cancer. Furthermore, it appears that circulating pepsinogens 1 and 2 may be independently associated with the risk of gastric cancer.