Prospective study of the association of gamma-glutamyltransferase with cancer incidence in women

Although several epidemiologic studies have shown that gamma-glutamyltransferase (GGT) is associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In experimental models the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it may thus play a role in tumor progression. In the present study, we investigated the association of GGT with overall and site-specific cancer incidence in a population-based cohort of 92,843 Austrian women with 349,674 serial GGT measurements, prospectively followed-up for a median of 13.5 years. The relationship between GGT and cancer incidence was analyzed using adjusted Cox regression models with age as underlying time metric with age as underlying time metric including GGT concentrations at baseline and incorporating repeated GGT measurements as a time-dependent variable. During follow-up, 4,884 incidence cancers were observed. Compared to normal low GGT (<17.99 U/L), cancer risk was elevated for all other GGT categories (p for trend < 0.0001), with adjusted hazard ratios (95% confidence intervals) of 1.06 (0.99-1.13) for GGT levels between 18.00 and 35.99 U/L (normal high), 1.12 (1.02-1.22) for GGT levels between 36.00 and 71.99 U/L (elevated) and 1.43 (1.28-1.61) for highly elevated GGT (>72.00 U/L). Very similar results were seen when GGT was analyzed as a time-dependent variable. In cancer-site specific models, elevated GGT statistically significantly increased the risk for malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, breast and female genital organs and lymphoid and haematopoietic cancers (all, p < 0.006). Our study is the first to demonstrate in a large population-based cohort that high GGT levels significantly increased cancer risk in women.     

Risk of cancer in first‐ and second‐degree relatives of testicular germ cell tumor cases and controls

Risk factors for testicular germ cell tumors (TGCT) have not been well identified; however, data suggest that risks of cancer in family members of men with TGCT is elevated. Using family history data from 738 cases and 904 controls enrolled in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study from 2002 to 2005, the risk of cancer in first‐ and second‐degree family members of these men was examined. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for reference age of case or control, race/ethnicity of case or control, sex of family member and lineage (maternal vs. paternal). An increased risk of all cancer among first‐degree relatives of cases compared to controls was observed (RR = 1.17, 95% CI: 1.01–1.35). There were suggestions of differences in risk when stratifying all relatives by lineage. For maternal relatives, there was a statistically significant increased risk of all cancer (RR = 1.16, 95% CI: 1.04–1.30), digestive tract (RR = 1.52, 95% CI: 1.15–2.00) and male genital organ cancer (RR = 1.70, 95% CI: 1.15–2.51); there was also a suggestion of increased risks of hematopoetic cancers, cancers in the female genital organs and nonmelanoma skin cancer. For paternal relatives, there was a statistically significant association only with decreased risk of lung cancer (RR = 0.69, 95% CI: 0.51–0.94). Thus, this study suggests that there may be aggregation of cancer among families of men diagnosed with TGCT. Published 2008 Wiley‐Liss, Inc.     

Association between height and thyroid cancer risk: A meta‐analysis of prospective cohort studies

While several epidemiological studies have investigated the relationship between height and risk for thyroid cancer, the results were inconsistent. In the present study, a systematic review and meta‐analysis of prospective cohort studies was conducted to assess the impact of height on thyroid cancer risk. Online databases were searched up to December 30, 2014, for prospective cohort studies on the association between height and thyroid cancer risk. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random‐effects model of meta‐analysis. In all, 11 articles were included in this meta‐analysis, including 15 prospective cohort studies, containing 6,695,593 participants and 7,062 cases of thyroid cancer. By comparing the highest versus the lowest categories of height, we reported that risk of thyroid cancer was increased with height in both men (summary RR = 1.40, 95%CI 1.09–1.78, p = 0.008) and women (summary RR = 1.54, 95%CI 1.30–1.83, p < 0.001). The summary RR of thyroid cancer per 5‐cm increase in height was 1.16 (95%CI 1.09–1.23, p < 0.001). The results were similar among men (per 5‐cm increase RR = 1.13, 95%CI 1.03–1.23, p = 0.011) and women (per 5‐cm increase RR = 1.18, 95%CI 1.10–1.27, p < 0.001). No obvious risk of publication bias was observed. Our meta‐analysis provides strong evidence for a dose–response relationship between height and risk of thyroid cancer in both men and women.     

Age at menarche and risk of ovarian cancer: A meta‐analysis of epidemiological studies

Epidemiological studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta‐analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two authors (T‐T.G. and Q‐J.W.) independently assessed eligibility and extracted data. We pooled the relative risks (RRs) from individual studies using a random‐effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case–control and five cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared to the youngest category) and ovarian cancer risk (RR = 0.85; 95% confidence interval [CI] = 0.75–0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case–control studies were 0.89 (95% CI = 0.76–1.03) and 0.84 (95% CI = 0.70–0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most subgroups; however, the significant association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta‐analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify these results by different cancer grading and histotype of ovarian cancer.     

Gamma-glutamyltransferase and risk of cancer in a cohort of 545,460 persons - the Swedish AMORIS study

Background

Apart from using gamma-glutamyltransferase (GGT) as a predictor of diabetes, cardiovascular and chronic kidney disease, some evidence suggests GGT as an indicator of cancer risk. We aimed to study the association between GGT and cancer in a large Swedish cohort with 37,809 primary cancers.

Methods

In a cohort of 545,460 persons (aged >20 years) who had a measurement of GGT in the Apolipoprotein Mortality Risk (AMORIS) study, multivariate Cox proportional hazards regression was used to investigate categories of GGT (<18, 18-36,36-72, ?72 U/L) in relation to cancer risk. Stratified analyses were conducted by gender, levels of alanine aminotransferase (ALT) (</?50 U/L), glucose (</?6.11 mmol/L) and triglycerides (</?1.71 mmol/L).

Results

A positive association was found between categories of GGT and overall cancer risk (HR: 1.07 (95%CI: 1.04-1.09,), 1.18 (1.14-1.22), 1.32 (1.26-1.38) for the 2nd, 3rd and 4th categories compared to the 1st). Stratified analyses showed that for those with glucose ?6.11 mmol/L, the association between GGT and risk of prostate, breast and liver cancer became stronger (e.g. HR for GGT ?72 U/L and prostate cancer: 1.11 (0.98-1.26) and 1.35 (1.00-1.81) for glucose <6.11 and ?6.11 mmol/L, respectively). With pancreatic cancer, the association with GGT was weaker for those with elevated glucose levels compared to those with normal levels. No effects of ALT or triglyceride levels on risk were found.

Conclusion

We found evidence of associations between elevated GGT and risk of developing different cancers. The strength of this association may vary by glucose levels because hyperglycaemia can result in oxidative stress initiating damaging pathways of carcinogenesis.     

Association between physical activity and all cancer mortality: Dose–response meta‐analysis of cohort studies

The relationship between physical activity (PA) before cancer diagnosis and all cancer mortality among the general population is not well defined because of inconsistent results from published studies. Thus, the lack of a meta‐analysis that addresses that issue prompted the current report. We conducted a literature search of PubMed and Web of Science to identify all relevant epidemiological studies published before February 28, 2015. We performed categorical and dose–response meta‐analyses to evaluate and quantify the association between pre‐diagnosis PA and all cancer mortality. A total of 32 prospective cohort studies involving 59,362 cancer deaths were included in this meta‐analysis. The pooled relative risks (RRs) of all cancer mortality were 0.80 [95% confidence interval (CI) = 0.76–0.85)] for highest versus lowest PA group and 0.85 (95% CI = 0.82–0.88) for PA versus non/occasional PA group. Dose–response analysis showed that the increment in pre‐diagnosis PA level was associated with a decreased risk of cancer death continuously. Moreover, an increment of 10 MET‐h/week was related to a 7% lower risk for all cancer mortality (RR = 0.93, 95% CI = 0.91–0.95). In conclusion, the present meta‐analysis provides evidence of an inverse association between pre‐diagnosis PA and all cancer mortality among the general population. High‐quality epidemiological studies that employ standardized PA assessments and unified definitions of PA levels should be developed in future.     

Dietary acrylamide and cancer risk: An updated meta‐analysis

The debate on the potential carcinogenic effect of dietary acrylamide is open. In consideration of the recent findings from large prospective investigations, we conducted an updated meta‐analysis on acrylamide intake and the risk of cancer at several sites. Up to July 2014, we identified 32 publications. We performed meta‐analyses to calculate the summary relative risk (RR) of each cancer site for the highest versus lowest level of intake and for an increment of 10 µg/day of dietary acrylamide, through fixed‐effects or random‐effects models, depending on the heterogeneity test. Fourteen cancer sites could be examined. No meaningful associations were found for most cancers considered. The summary RRs for high versus low acrylamide intake were 0.87 for oral and pharyngeal, 1.14 for esophageal, 1.03 for stomach, 0.94 for colorectal, 0.93 for pancreatic, 1.10 for laryngeal, 0.88 for lung, 0.96 for breast, 1.06 for endometrial, 1.12 for ovarian, 1.00 for prostate, 0.93 for bladder and 1.13 for lymphoid malignancies. The RR was of borderline significance only for kidney cancer (RR = 1.20; 95% confidence interval, CI, 1.00–1.45). All the corresponding continuous estimates ranged between 0.95 and 1.03, and none of them was significant. Among never‐smokers, borderline associations with dietary acrylamide emerged for endometrial (RR = 1.23; 95% CI, 1.00–1.51) and ovarian (RR = 1.39; 95% CI, 0.97–2.00) cancers. This systematic review and meta‐analysis of epidemiological studies indicates that dietary acrylamide is not related to the risk of most common cancers. A modest association for kidney cancer, and for endometrial and ovarian cancers in never smokers only, cannot be excluded.     

High hemoglobin A1c levels within the non‐diabetic range are associated with the risk of all cancers

Previous studies have reported associations between diabetes and cancer risk. However, specific association of hemoglobin A1c (HbA1c) levels with cancer risk remains inconclusive. We followed 29,629 individuals (11,336 men; 18,293 women) aged 46–80 years who participated in the Japan Public Health Center‐based prospective study who had HbA1c measurements available and were cancer‐free at baseline. Cancer incidence was assessed by systemic surveys. We estimated hazard ratios (HRs) for cancer risk with adjustment for age sex, geographic area, body mass index, smoking status, physical activity, alcohol, coffee, vegetable and total energy consumption, and history of cardiovascular disease. After a median follow‐up of 8.5 years, 1,955 individuals had developed cancer. Higher HbA1c levels within both the non‐diabetic and diabetic ranges in individuals without known diabetes were associated with overall cancer risk. Compared with individuals without known diabetes and HbA1c levels of 5.0–5.4%, the HRs for all cancers were 1.27 (95% confidence interval, 1.07–1.52); 1.01 (0.90–1.14); 1.28 (1.09–1.49); and 1.43 (1.14–1.80) for individuals without known diabetes and HbA1c levels <5.0%, 5.5–5.9%, 6.0–6.4%, and ≥6.5%, respectively, and 1.23 (1.02–1.47) for individuals with known diabetes. The lowest HbA1c group had the highest risk of liver cancer, and HbA1c levels were linearly associated with the risk of all cancers after excluding liver cancer (P for linear trend, 0.004). In conclusion, our findings corroborate the notion that glycemic control in individuals with high HbA1c levels may be important not only to prevent diabetes but also to prevent cancer.     

γ‐Glutamyltransferase and cancer risk: The Korean cancer prevention study

Elevated serum γ‐glutamyltransferase (GGT) is a marker of hepatic injury and is associated with risk of chronic disease. However, the value of GGT as a biomarker for cancer risk remains unclear. Therefore, we evaluated the association of serum GGT with cancer incidence among more than 1.6 million Koreans. We included 1,662,087 Koreans (1,108,121 men and 553,966 women aged 20–95 years) who received health insurance from the National Health Insurance Service and had a biennial medical evaluation between 1995 and 1998. Follow‐up was through December 2012. Using Cox proportional hazards models, we adjusted for age, smoking status, alcohol consumption, exercise and body mass index after exclusion of early cases (cancer diagnosis or death within 5 years of starting follow‐up) and estimated hazard ratios (HRs) of overall and organ‐specific cancer incidence by GGT quintiles. During the 17‐year follow‐up, 129,087 new cancer cases occurred among the participants. Across levels of GGT, there was a positive gradient of HR and the highest quintile of GGT (≥60 IU/L) had the highest HR for all cancers in both men and women. By cancer site, the association was strongest for liver cancer, comparing the highest and lowest strata in men [HR, 6.67; 95% confidence interval (95%CI), 5.88–7.57] and in women (HR, 7.57; 95%CI, 6.41–8.94). Significant associations were also observed for cancers of the esophagus, larynx, stomach, colorectal, bile duct and lung in men and of the bile duct in women. Increased serum GGT level is independently associated with risk of cancer.     

Citrus consumption and cancer incidence: the Ohsaki cohort study

Basic research and case–control studies have suggested that citrus consumption may protect against cancer. However, the protective effect has been observed from few prospective studies. This study investigated the association of citrus consumption with cancer incidence among 42,470 Japanese adults in the Ohsaki National Health Insurance Cohort, which covered an age range of 40–79 years, and was followed up from 1995 to 2003 for all‐cancer and individual cancer incidence. Citrus consumption was assessed using a self‐administered questionnaire. The Cox proportional hazard model was applied to estimate relative risks (RRs) and 95% CIs. During the 323,204 person‐years of follow‐up, 3,398 cases were identified totally. Citrus consumption, especially daily consumption, was correlated with reduced all‐cancer incidence, the RRs were 0.89 (95% CI = 0.80–0.98) for total participants, 0.86 (0.76–0.98) for males and 0.93 (0.79–1.09) for females, as well as multiple cancers at individual sites, especially pancreatic (RR = 0.62, 95% CI = 0.38–1.00) and prostate cancer (RR = 0.63, 95% CI = 0.41–0.97). Joint effect analysis showed a reduced risk of overall cancer existed only for subjects who consumed ≥1 cup green tea/day (RR = 0.83, 95% CI = 0.73–0.93) as well as for males (RR = 0.83, 95% CI = 0.71–0.97) or females (RR = 0.82, 95% CI = 0.68–0.99). These findings suggest that citrus consumption is associated with reduced all‐cancer incidence, especially for subjects having simultaneously high green tea consumption. Further work on the specific citrus constituents is warranted, and clinical trials are ultimately necessary to confirm the protective effect.     

Gamma‐glutamyltransferase and risk of prostate cancer: Findings from the KIHD prospective cohort study

Increased circulating serum gamma‐glutamyltransferase (GGT) has been linked with an increased risk of chronic disease outcomes, including overall and several site‐specific cancers. However, the relationship of GGT with prostate cancer risk is uncertain. We aimed to assess the prospective association of GGT with risk of prostate cancer. Serum GGT activity was assessed at baseline in the Finnish Kuopio Ischemic Heart Disease prospective cohort of 2,390 men aged 42–61 years without a history of cancer at baseline. We corrected for within‐person variability in GGT values using data from repeat measurements taken several years apart. During a median follow‐up of 24.6 years, 230 cases of prostate cancer occurred. The age‐adjusted regression dilution ratio for log_e GGT was 0.69 [95% confidence interval (CI): 0.63–0.74]. Serum GGT was nonlinearly associated with risk of prostate cancer. In age‐adjusted Cox regression analysis, the hazard ratio (95% CIs) for prostate cancer in a comparison of the top quartile versus bottom quartiles 1–3 of GGT values was 1.43 (1.07 to 1.93; p = 0.017), which persisted on adjustment for several established cancer risk factors 1.46 (1.06 to 2.02; p = 0.020). The association remained unchanged on further adjustment for total energy intake, socioeconomic status, physical activity and C‐reactive protein. The association did not importantly vary across several clinical subgroups. GGT is positively and independently associated with future risk of prostate cancer in a middle‐aged Finnish male population over long‐term follow‐up. Further research is needed to understand the mechanistic pathways involved and if GGT may have potential relevance in prostate cancer prevention.     

Body fatness at an early age and risk of colorectal cancer

While there is convincing evidence that excess body fatness in adulthood is positively associated with colorectal cancer risk, the association between body fatness at an early age (≤30 years) and the risk of colorectal cancer has been equivocal. The present meta‐analysis was performed to clarify this association. PubMed and Web of Science databases were searched for relevant studies that investigated this association. The risk estimates from each study were transformed into a continuous variable for each 5 kg/m² increase in body mass index (BMI). A random effects model was used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs). A total of 15 observational studies (13 cohort studies and two case‐control studies) were included in this meta‐analysis. Each 5 kg/m² increase in BMI was significantly associated with a 13% (RR 1.13, 95% CI 1.08, 1.19), 17% (RR 1.17, 95% CI 1.09, 1.25) and 8% (RR 1.08, 95% CI 1.04, 1.11) higher risk of colorectal cancer overall, in men, and in women, respectively. Substantial heterogeneity was observed across studies. Based on the anatomic subsite, each 5 kg/m² increase in BMI was significantly associated with a 14% (RR 1.14, 95% CI 1.07, 1.22) higher risk of colon cancer, whereas no association (RR 1.03, 95% CI 0.95, 1.13) was observed with rectal cancer. In summary, body fatness at an early age may affect colon cancer risk later in life. Prevention of overweight and obesity in young individuals should be emphasized to prevent early‐onset colon cancer attributed to excess body fatness.     

Alcohol consumption and gastric cancer risk—A pooled analysis within the StoP project consortium

An association between heavy alcohol drinking and gastric cancer risk has been recently reported, but the issue is still open to discussion and quantification. We investigated the role of alcohol drinking on gastric cancer risk in the “Stomach cancer Pooling (StoP) Project,” a consortium of epidemiological studies. A total of 9,669 cases and 25,336 controls from 20 studies from Europe, Asia and North America were included. We estimated summary odds‐ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study‐specific ORs using random‐effects meta‐regression models. Compared with abstainers, drinkers of up to 4 drinks/day of alcohol had no increase in gastric cancer risk, while the ORs were 1.26 (95% CI, 1.08–1.48) for heavy (>4 to 6 drinks/day) and 1.48 (95% CI 1.29–1.70) for very heavy (>6 drinks/day) drinkers. The risk for drinkers of >4 drinks/day was higher in never smokers (OR 1.87, 95% CI 1.35–2.58) as compared with current smokers (OR 1.14, 95% CI 0.93–1.40). Somewhat stronger associations emerged with heavy drinking in cardia (OR 1.61, 95% CI 1.11–2.34) than in non‐cardia (OR 1.28, 95% CI 1.13–1.45) gastric cancers, and in intestinal‐type (OR 1.54, 95% CI 1.20–1.97) than in diffuse‐type (OR 1.29, 95% CI 1.05–1.58) cancers. The association was similar in strata of H. pylori infected (OR = 1.52, 95% CI 1.16–2.00) and noninfected subjects (OR = 1.69, 95% CI 0.95–3.01). Our collaborative pooled‐analysis provides definite, more precise quantitative evidence than previously available of an association between heavy alcohol drinking and gastric cancer risk.     

Dietary total fat and fatty acids intake,serum fatty acids and risk of breast cancer: A meta‐analysis of prospective cohort studies

Results from prospective cohort studies on the association between dietary total fat and fatty acids intake and risk of breast cancer remain controversial. Pertinent prospective cohort studies were identified by a search of Embase and PubMed from inception to September 2015. Study‐specific relative risks (RRs) with 95% confidence intervals were pooled using a random‐effect model. Between‐study heterogeneity and publication bias were assessed, and sensitivity analysis was conducted. Twenty‐four independent studies on dietary total fat and fatty acids intake and seven studies on serum fatty acids were included. The pooled RR of breast cancer for the highest vs. lowest category of dietary total fat intake was 1.10 (1.02–1.19); however, no association was observed in studies adjusting for traditional risk factors of breast cancer. No association was observed between animal fat, vegetable fat, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n‐3 PUFA, n‐6 PUFA, eicosapentaenoic acid, docosahexaenoic acid, alpha‐linolenic acid, oleic acid, linoleic acid and arachidonic acid and risk of breast cancer. The pooled RRs of breast cancer for the highest vs. lowest category of serum SFA, MUFA, PUFA, n‐3 PUFA and n‐6 PUFA were 1.00 (0.78–1.28), 1.41 (0.99–2.03), 0.59 (0.27–1.30), 0.81 (0.60–1.10) and 0.84 (0.60–1.18), respectively. Results from this meta‐analysis suggested that dietary total fat and fatty acids might be not associated with risk of breast cancer.     

Association between dietary vitamin C intake and risk of esophageal cancer: A dose–response meta‐analysis

While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta‐analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random‐effects model. Dose–response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta‐analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49–0.68, I² = 56%]. A linear dose–response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80–0.93, p_linearity = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer.     

Alcohol consumption‐associated breast cancer incidence and potential effect modifiers: the Japan Public Health Center‐based Prospective Study

Epidemiological studies have evaluated whether the impact of alcohol intake on breast cancer risk is modified by use of exogenous estrogens, folate intake, body weight and smoking status, but results have been inconsistent. Further, effect modification by intake of isoflavones and alcohol‐induced facial flushing, which are prevalent in Asian populations, have not been investigated. We investigated the association between alcohol intake and breast cancer risk and whether the association is modified by these factors among 50,757 premenopausal and postmenopausal women (aged 40–69 years) in the population‐based Japan Public Health Center‐based Prospective Study. Alcohol consumption and other related factors were assessed using self‐reported questionnaires. Through to the end of 2006, 572 patients were identified. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by hazard ratios derived from Cox proportional hazards regression models. Compared with never‐drinkers, regular alcohol drinkers (>150 g of ethanol/week) had a higher risk of the development of breast cancer; the multivariable‐adjusted RRs were 1.75 (95% CI = 1.16–2.65; p_trend = 0.035) for overall, 1.78 (95% CI = 1.09–2.90) for premenopausal and 1.21 (95% CI = 0.53–2.75) for postmenopausal women. There was no statistical evidence for effect modification by menopausal status, use of exogenous estrogens, intakes of isoflavone and folate, body weight, alcohol‐induced facial flushing or smoking (All p_interactions ≥ 0.15). Excessive alcohol intake was associated with an increase in the risk of breast cancer in this population. There was no statistical evidence for effect modification.     

Type 2 diabetes mellitus,insulin‐use and risk of bladder cancer in a large cohort study

Type 2 diabetes mellitus (T2DM) is associated with increased bladder cancer incidence in some, but not all, studies. Many studies had limited statistical power and few examined risk by insulin‐use, duration of diabetes or cancer stage. We examined the association between T2DM and bladder cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a large prospective study with information on insulin‐use and duration of diabetes. Diabetes and insulin‐use were ascertained from a questionnaire at study enrollment in 1992 or 1993 and updated in 1997 and every 2 years thereafter. During follow‐up through 2007, 1,852 cases of incident bladder cancer were identified among 172,791 participants. Multivariable adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using extended Cox regression modeling. There were no associations of T2DM with the risk of bladder cancer overall (RR = 1.01, 95% CI: 0.87–1.17), noninvasive disease (RR = 0.93, 95% CI: 0.76–1.14) or invasive disease (RR = 1.13, 95% CI: 0.91–1.40). Compared to participants without T2DM, risk of invasive bladder cancer was higher among participants who had had T2DM for >15 years (RR = 1.63, 95% CI: 1.09–2.43) and among those using insulin (RR = 1.64, 95% CI: 1.18–2.27). These results do not support an association of T2DM with overall bladder cancer incidence, but do suggest positive associations of long‐term T2DM and insulin‐use or other factors correlated with severe diabetes, with invasive bladder cancer incidence.     

Concordant and discordant familial cancer: Familial risks,proportions and population impact

Relatives of cancer patients are at an increased risk of the same (concordant) cancer but whether they are at a risk for different (discordant) cancers is largely unknown – beyond well characterized hereditary cancer syndromes ‐ but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing familial risks when family members were diagnosed with any discordant cancers. We compared the population impact of concordant to discordant familial cancer. The Swedish Family‐Cancer Database (FCD) was used to calculate familial relative risks (RRs) for family members of cancer patients, for the 27 most common cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant cancers in the family were detected as significant risk factors for the majority of cancers, although the corresponding RRs were modest compared to RRs for concordant cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid cancers (3.28), when 5 or more family members were diagnosed with discordant cancers. For most cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many cancers will be a challenge.     

Meta‐analysis of the association between dietary inflammatory index (DII) and cancer outcomes

Proinflammatory dietary patterns have been associated with increased cancer risk and mortality. We present a systematic review and meta‐analysis of the current published literature on a dietary inflammatory index (DII) score and its association with cancer risk and mortality outcomes. Published articles from online databases (PubMed, Scopus, and Embase) examining the association between DII and any cancer risk, incidence, or mortality between 1980 and November 2016 were selected for review. Results of studies meeting inclusion criteria were summarized and meta‐analyzed using STATA to generate summary measures of association across studies. Sixty‐three published articles were identified from the search, and following title, abstract and full‐text review, twenty‐four studies met inclusion criteria. All articles calculated DII scores based on study‐specific food‐frequency questionnaires using methodology from the same article. Of the 24 included studies, 13 were case–control, 6 were prospective cohort, 1 was a retrospective cohort, 3 were RCTs, and 1 did not specify study design. The most common cancers examined were colorectal, breast, lung, and prostate. Individuals in the highest versus lowest DII categories had 25% increased risk of overall cancer incidence (RR: 1.25, 95% CI: 1.16–1.35), 75% higher odds of cancer (OR: 1.75, 95% CI: 1.43–2.16) and 67% increased risk of cancer mortality (RR: 1.67, 95% CI: 1.13–2.48). Upon stratification for cancer type, positive associations remained (RR_breast: RR: 1.12, 95% CI: 1.03–1.22) (RR_colorectal: 1.33, 95% CI: 1.22–1.46) (RR_lung: 1.30, 95% CI: 1.13–1.50). There were consistent and significant positive associations between higher DII and cancer incidence and mortality across cancer types, study populations, and study design.     

Association of gamma-glutamyltransferase and risk of cancer incidence in men: a prospective study

Although several epidemiologic studies have shown that gamma-glutamyltransferase (GGT) is independently associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In several experimental models, the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it thus may play a role in tumor progression, as has been repeatedly suggested. We prospectively investigated the association between GGT and risk of overall and site-specific cancer incidence in a large population-based cohort of 79,279 healthy Austrian men with serial GGT measurements. Median follow-up was 12.5 years. Adjusted Cox proportional hazards models were calculated to evaluate GGT as an independent predictor for cancer incidence, and nonparametric regression splines were fitted to flexibly capture the dose-response relationship. Elevated GGT significantly increased overall cancer risk, showing a clear dose-response relationship (P for GGT log-unit increase < 0.0001; P for trend < 0.0001). In comparison with the reference GGT concentration (25 units/L), we found adjusted relative risks (95% confidence intervals) equalling 1.19 (1.15-1.22) for GGT concentrations of 60 units/L, 1.32 (1.28-1.36) for 100 units/L, 1.67 (1.60-1.75) for 200 units/L, and 2.30 (2.14-2.47) for 400 units/L. In cancer site-specific models, GGT was significantly associated with malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, and urinary organs (all P < 0.0001). Age of participants significantly modified the association of GGT and cancer risk (P < 0.001), revealing markedly stronger associations in participants ages 相似文献