Population‐based cohort studies of type 2 diabetes and stomach cancer risk in Chinese men and women

Although positive associations have been found for diabetes and a number of cancer sites, investigations of stomach cancer are limited and the results lack consistency. In this prospective study we investigated the relationship between type 2 diabetes mellitus (T2DM) and stomach cancer risk in mainland China. We assessed the associations among T2DM, T2DM duration, and stomach cancer risk in two prospective population‐based cohorts, the Shanghai Women's Health Study and the Shanghai Men's Health Study. Included in the study were 61 480 men and 74 941 women. Stomach cancer cases were identified through annual record linkage to the Shanghai Cancer Registry, and verified through home visits and review of medical charts. After a median follow‐up of 7.5 years for the Shanghai Men's Health Study and 13.2 years for the Shanghai Women's Health Study, a total of 755 incident cases of stomach cancer (376 men and 379 women) were identified through to September 2013. Overall, we did not find any evidence that T2DM was associated with an increased risk of stomach cancer either in men (multi‐adjusted hazard ratio = 0.83, 95% confidence interval, 0.59–1.16) or in women (multi‐adjusted hazard ratio = 0.92, 95% confidence interval, 0.68–1.25). Our findings from two large prospective population‐based cohorts suggest that T2DM was not associated with stomach cancer risk.     

Detection bias may be the main cause of increased cancer incidence among diabetics: Results from the Rotterdam Study

AimType 2 diabetes is associated with an increased cancer risk. Most studies on this topic analyse diabetes as a risk factor without adjusting for diabetes duration before cancer occurrence. This study aimed to investigate the association between diabetes duration and cancer risk in more detail.MethodsIn this prospective cohort study, diabetes diagnosis was based on clinical information and use of glucose lowering medication. Details on incident cancers were obtained via general practitioners and linkage to pathology registers. Cox proportional hazards models were used with onset and duration of diabetes as time-varying determinants.ResultsThe study comprised 10,181 individuals. Diabetes was associated with an increased overall risk of incident cancers (hazard ratio (HR) 1.2, 95% confidence interval (CI) 1.07–1.39) and pancreatic cancer (HR 2.9, 95% CI 1.75–4.89). A diagnosis of diabetes less than three months before the diagnosis of cancer was associated with strongly increased risks of all- (HR 3.3, 95% CI 2.50–4.32) and pancreatic cancers (HR 28.7, 95% CI 6.32–130.58).ConclusionThe magnitude of the association between diabetes and an increased risk of cancer seems to be inflated by detection- or protopathic bias. Future studies investigating this association should adjust for diabetes duration and include a plausible aetiological risk window.     

Impact of detection bias on the risk of gastrointestinal cancer and its subsites in type 2 diabetes mellitus

BackgroundType 2 diabetes mellitus (T2DM) may be a risk factor for gastrointestinal (GI) cancers, but variations in study designs of observational studies may have yielded biased results due to detection bias. Furthermore, differences in risk for GI cancer subsites have not been extensively evaluated. We aimed to determine the risk of GI cancer and its subsites in patients with T2DM and how it is affected by detection bias.MethodsA matched cohort study was performed using the NCR-PHARMO database. New-users of ≥1 non-insulin anti-diabetic drug during 1998–2011 were matched with non-diabetic controls by year of birth, sex, and time between database entry and index. Cox regression analyses were performed with and without lag-period to estimate hazard ratios (HRs) for GI cancer and its subsites. Covariables included age, sex, use of other drugs and history of hospitalisation.ResultsAn increased risk of GI cancer was observed in T2DM patients (HR 1.5, 95% confidence interval [CI] 1.3–1.7) compared with controls, which was attenuated in the 1-year lagged analysis (HR 1.4, 95% CI 1.2–1.7). Stratified by subsite, statistically significant increased risks of pancreatic (HR 4.7, 95% CI 3.1–7.2), extrahepatic bile duct (HR 4.2, 95% CI 1.5–11.8) and distal colon cancer (HR 1.5, 95% CI 1.1–2.1) were found, which remained statistically significantly increased in the lagged analysis.ConclusionsT2DM patients had a 40% increased risk of GI cancer. Increased GI cancer risks tended to be weaker when reducing detection bias by applying a 1-year lag-period. Future observational studies should therefore include sensitivity analyses in which this bias is minimised.     

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.     

Modest increase in risk of specific types of cancer types in type 2 diabetes mellitus patients

Most studies associated diabetes mellitus (DM) with risk of cancer have focused on the Caucasian population and only a few types of cancer. Therefore, a large and comprehensive nationwide retrospective cohort study involving an Asian population was conducted to evaluate the risk of several major types of cancer among Type 2 DM patients. The study analyzed the nationwide population‐based database from 1996 to 2009 released by the National Health Research Institute in Taiwan. Incidence and hazard ratios (HRs) were calculated for specific types of cancer. The overall risk of cancers was significantly greater in the DM cohort [N = 895,434; HR = 1.19, 95% confidence interval (CI) = 1.17–1.20], compared with non‐DM controls (N = 895,434). Several organs in the digestive and urogenital systems showed increased risk of cancer. The three highest HRs were obtained from cancers of the liver (HR = 1.78, 95% CI = 1.73–1.84), pancreatic (HR = 1.52, 95% CI = 1.40–1.65), and uterus and corpus (HR = 1.38, 95% CI = 1.22–1.55). The risk increased with age, and men with DM aged ≥75 years exhibited the highest risk (HR = 7.76, 95% CI = 7.39–8.15). Subjects with DM in this population have a modest increased risk of cancer, similar to the Caucasian population for several specific types of cancer. Old men with DM have the highest risk of cancer. Careful screening for cancer in DM patients is important for early diagnosis and effective treatment.     

Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994–2016) and the NHSII (1995–2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81–1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90–1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74–1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48–0.94), current use (HR = 1.01; 95% CI = 0.80–1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95–1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.     

Type 2 diabetes,adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting

Type 2 diabetes (T2D) and adiposity associate with increased risk of several cancers, but the impact of competing risk of noncancer deaths on these associations is not known. We prospectively examined participants in the Malmö Diet and Cancer Study aged 44–73 years with no history of cancer at baseline (n = 26,953, 43% men). T2D was ascertained at baseline and during follow‐up, and body mass index (BMI) and waist circumference (WC) at baseline. Multivariable cause‐specific hazard ratios (HR) and subdistribution hazard ratios (sHR), taking into account noncancer deaths, were estimated using Cox‐ and competing risk regression. During follow‐up (mean 17 years), 7,061 incident cancers (3,220 obesity‐related cancer types) and 2,848 cancer deaths occurred. BMI and WC were associated with increased risk of obesity‐related cancer incidence and cancer mortality. In T2D subjects, risk of obesity‐related cancer was elevated among men (HR = 1.31, 95% CI: 1.12–1.54; sHR = 1.29, 95% CI: 1.10–1.52), and cancer mortality among both men and women (HR = 1.34, 95% CI: 1.20–1.49; sHR = 1.30, 95% CI: 1.16–1.45). There was no elevated actual risk of cancer death in T2D patients with long disease duration (sHR = 1.00, 95% CI: 0.83–1.20). There was a significant additive effect of T2D and adiposity on risk of obesity‐related cancer and cancer mortality. In conclusion, detection bias may partially explain the increased risk of cancer morbidity among T2D patients. Both excess risk of competing events among patients with T2D and depletion of susceptibles due to earlier cancer detection will lower the actual risk of cancer, particularly with longer diabetes duration and at older ages.     

Prospective study of Type 2 diabetes mellitus,anti‐diabetic drugs and risk of prostate cancer

Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti‐diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD = 9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD = 3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR = 0.85, 95% CI = 0.82–0.88) but among men with T2DM, those on metformin had no decrease (HR = 0.96, 95% CI = 0.77–1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR = 0.73, 95% CI = 0.55–0.98), compared to men with T2DM not on anti‐diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR = 1.11, 95% CI = 0.95–1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.     

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

BackgroundDietary 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 methodsA 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.ResultsAfter 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.ConclusionsThere is little evidence that dietary GI, GL, or carbohydrates affect the incidence of liver cancer in this Asian population.     

Serum glucose and hemoglobin A1C levels at cancer diagnosis and disease outcome

BackgroundDespite the lack of scientific data, many cancer patients hold the belief that glucose ‘feeds’ cancer and might affect disease outcome. We aimed to evaluate associations between glucose, hemoglobin A1C (HbA1C), and survival among individuals with diabetes and diabetes associated cancers.MethodsFive retrospective cohort studies were conducted in a large population-representative database. The study population included all patients with diabetes and an incident diagnosis of colorectal, breast, bladder, pancreatic and prostate cancers. Exposure of interest was serum glucose or HbA1C levels within 6 months prior to cancer diagnosis. Cox regression model was used to calculate hazard-ratio (HR) and 95% confidence-interval (CI) for overall survival. Analyses were adjusted for cancer-specific confounders. A subgroup analysis was performed among insulin-treated patients.ResultsStudy cohorts included 7916 individuals with incident cancers and concurrent diabetes. There was no association between HbA1C levels and overall survival in colorectal (HR 1.00, 95% CI 0.95–1.06), breast (HR 1.03, 95% CI 0.95–1.11), bladder (HR 0.94, 95% CI 0.86–1.01), pancreatic (HR 0.98, 95% CI 0.94–1.02), or prostate (HR 1.02, 95% CI 0.96–1.08) cancers. Among diabetes patients treated with insulin, there was increased survival with increasing serum glucose, most prominent for bladder cancer (HR 0.91, 95% CI 0.84–0.99, per 1 mmol/l increase).ConclusionsHigher glucose and HbA1C levels in diabetes patients with incident cancer are not associated with worse overall survival following cancer diagnosis. Among insulin-treated patients, higher glucose levels may be associated with improved survival.     

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case‐control study

Relationship on new statin use and the risk of hepatocellular carcinoma (HCC) in patients with incident type 2 diabetes mellitus (T2DM), who might be at the risk of developing HCC, is uncertained. A nationwide population–based nested case–control study was conducted within the National Health Insurance Service National Sample Cohort 2002–2013 in Korea. Newly prescribed statin after newly diagnosed T2DM was defined as statin use. Controls were matched to case patients on age, sex, follow–up time, and the date of diabetes diagnosis at a five–to–one ratio. Odds ratios (ORs) for associations of statin use with HCC were calculated using conditional logistic regression. After at least a 5‐year HCC–free period, there were 229 incident HCC cases and 1,145 matched controls from 47,738 patients with incident diabetes. Of these 229 incident HCC cases, 27 (11.8%) were statin users, whereas 378 (33.0%) were statin users among 1,145 controls. Statin use was associated with a reduced risk of HCC development (adjusted OR [AOR]= 0.36, 95% confidence interval [CI] 0.22–0.60) after adjustment for chronic viral hepatitis, liver cirrhosis, alcoholic liver disease, previous cancer, aspirin use, insulin use, sulfonylurea use, metformin use, thiazolidinedione use, history of chronic obstructive pulmonary disease, Charlson comorbidity score, household income level, and residential area. Risk reduction was accentuated with an increase of cumulative defined daily doses (cDDD) compared with non–users (AORs 0.53, 0.36, 0.32, and 0.26 in ≤60, 60–180, 181–365, and >365cDDD, respectively; P for trend <0.0001). The risk reduction was apparent in the presence of liver disease (AOR = 0.27, 95% CI 0.14–0.50), including heterogeneous groups of clinical diagnosis of liver disease, but not significant in the absence of liver disease (AOR = 0.64, 95% CI 0.32–1.29). Among patients with new onset T2DM, statin use before HCC diagnosis may have a beneficial inhibitory effect on HCC development in a dose–dependent manner, especially in individuals with liver disease.     

Diabetes,metformin and cancer risk in myotonic dystrophy type I

Myotonic dystrophy type I (DM1) is an autosomal dominant multisystem disorder characterized by myotonia and muscle weakness. Type 2 diabetes (T2D) and cancer have been shown to be part of the DM1 phenotype. Metformin, a well-established agent for the management of T2D, is thought to have cancer-preventive effects in the general population. In our study, we aimed to assess the association between T2D, metformin use and the risk of cancer in DM1 patients. We identified a cohort of 913 DM1 patients and an age-, sex- and clinic-matched cohort of 12,318 DM1-free controls from the UK Clinical Practice Research Datalink, a large primary care records database. We used Cox regression models to assess cancer risk in T2D patients who were metformin users or nonusers compared to patients without T2D. Separate analyses were conducted for DM1 patients and controls. T2D was more prevalent in DM1 than in controls (8% vs. 3%, p < 0.0001). DM1 patients with T2D, compared to those without T2D, were more likely to develop cancer (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 1.18–10.97; p = 0.02), but not if they were treated with metformin (HR = 0.43, 95% CI = 0.06–3.35; p = 0.42). Among controls, we observed no significant associations between T2D and cancer risk in either users or nonusers of Metformin (HR = 1.28, 95% CI = 0.91–1.79; p = 0.16 and HR = 1.13, 95% CI = 0.72–1.79; p = 0.59, respectively). These results show an association between T2D and cancer risk in DM1 patients and may provide new insights into the possible benefits of Metformin use in DM1.     

Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus

BackgroundWhether metformin therapy affects incident prostate cancer risk in Asian patients with type 2 diabetes mellitus (T2DM) has not been investigated.MethodsThe National Health Insurance reimbursement database of Taiwanese male patients with new-onset T2DM between 1998 and 2002 and aged ⩾40 years (n = 395,481) were retrieved to follow up prostate cancer incidence until the end of 2009. Metformin was treated as a time-dependent variable. Of the patients studied, 209,269 were never-users and 186,212 were ever-users. A time-dependent approach was used to calculate prostate cancer incidence and estimate hazard ratios using Cox regression for ever-users, never-users and subgroups of metformin exposure (tertiles of cumulative duration and cumulative dose). Sensitivity analyses were conducted in various subgroups, using time-dependent and non-time-dependent approaches.ResultsDuring the follow-up, 2776 metformin ever-users and 9642 never-users developed prostate cancer, representing an incidence of 239.42 and 737.10 per 100,000 person-years, respectively. The hazard ratio (95% confidence intervals) after adjustment for propensity score (PS) for ever- versus never-users was 0.467 (0.446–0.488). The PS-adjusted hazard ratios for the first, second and third tertiles of cumulative duration of metformin therapy were 0.741 (0.698–0.786), 0.474 (0.441–0.508) and 0.231 (0.212–0.253), respectively (P-trend < 0.001); and were 0.742 (0.700–0.786), 0.436 (0.406–0.468) and 0.228 (0.208–0.251) for the respective cumulative dose (P-trend < 0.001). Sensitivity analyses consistently supported a protective effect of metformin on incident prostate cancer.ConclusionsMetformin use is associated with a decreased risk of incident prostate cancer in Taiwanese male patients with T2DM.     

Dietary trace element intake and liver cancer risk: Results from two population‐based cohorts in China

Dietary factors have been hypothesized to affect the risk of liver cancer via various mechanisms, but the influence has been not well studied and the evidence is conflicting. We investigated associations of dietary trace element intake, assessed through a validated food frequency questionnaire, with risk of liver cancer in two prospective cohort studies of 132,765 women (1997–2013) and men (2002–2013) in Shanghai, China. The associations were first evaluated in cohort studies and further assessed in a case–control study nested within these cohorts adjusting for hepatitis B virus infection. For cohort analyses, Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. For nested case–control analyses, conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After a median follow‐up time of 15.2 years for the Shanghai Women's Health Study and 9.3 years for the Shanghai Men's Health Study, 192 women and 344 men developed liver cancer. Dietary intake of manganese was inversely associated with liver cancer risk (highest vs. lowest quintile, HR = 0.51, 95% CI: 0.35–0.73; p_trend = 0.001). Further adjustment for hepatitis B virus infection in the nested case–control study yielded a similar result (highest vs. lowest quintile, OR = 0.38, 95% CI: 0.21–0.69; p_trend < 0.001). No significant association was found between dietary intake of selenium, iron, zinc, copper and liver cancer risk. The results suggest that higher intake of manganese may be associated with a lower risk of liver cancer in China.     

Diabetes mellitus,genetic variants in the insulin-like growth factor pathway and colorectal cancer risk

Genetic variation in the insulin-like growth factor (IGF) pathway may further increase the risk of colorectal cancer (CRC) associated with type 2 diabetes mellitus (T2DM). Joint effects of T2DM and genetic variation in the IGF pathway on CRC risk can increase mechanistic insights. Participants from the Netherlands Cohort Study (n = 120, 852) completed a baseline questionnaire in 1986 when 55–69 years old (case–cohort, n_subcohort = 5,000, n_cases = 3,441 after 16.3 years follow-up). Self-reported DM at baseline with onset at ≥30 years was classified as T2DM. Eighteen single nucleotide polymorphisms (SNPs) from the IGF pathway were aggregated in a genetic risk score (GRS). Cox proportional hazard ratios (HRs) for CRC were estimated according to combinations of T2DM status with GRS tertiles and categories of an IGF1 19-CA repeat polymorphism. Baseline T2DM prevalence was 3.1% in subcohort members and 3.8% in CRC cases. Comparison of combined categories with non-T2DM individuals in the lowest GRS tertile as reference showed that those in the highest GRS tertiles with and without T2DM had significantly increased CRC risks, particularly those with T2DM (HR = 2.28, 95% CI: 1.11, 4.66). As compared to IGF1 19-CA wild-type carriers without T2DM, carrying two IGF1 19-CA variant repeat alleles were associated with a significantly decreased CRC risk in those without T2DM (HR = 0.76, 95% CI: 0.63–0.91). This association was absent when T2DM was present. Our study of joint effects indicated that the presence of unfavorable alleles in the IGF pathway may further increase the risk of CRC associated with T2DM.     

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

BackgroundEpidemiological studies evaluating the association between cruciferous vegetables (CVs) intake and female lung cancer risk have produced inconsistent results.Patients and methodsThis 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.ResultsAfter 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.ConclusionsOur study suggests that CV consumption may reduce the risk of lung cancer in women, particularly among never smokers.     

Dietary B vitamin and methionine intakes and lung cancer risk among female never smokers in China

Purpose

B vitamins and methionine have been postulated to have potential effects on carcinogenesis; however, findings from previous epidemiologic studies on B vitamins, methionine, and lung cancer risk are inconsistent. We investigated associations of dietary intakes of B vitamins (i.e., riboflavin, niacin, vitamin B6, folate, and vitamin B12) and methionine with lung cancer risk among female never smokers.

Methods

The Shanghai Women’s Health Study, a population-based, prospective cohort study, included 74,941 women. During a median follow-up of 11.2?years, 428 incident lung cancer cases accrued among 71,267 women with no history of smoking or cancer at baseline. Baseline dietary intakes were derived from a validated, interviewer-administered food frequency questionnaire. Cancer incidence and vital status were ascertained through annual linkage to the Shanghai Cancer Registry and Shanghai Vital Statistics Registry databases and through biennial in-person follow-ups with participants. Adjusted hazard ratios (HR) and 95?% confidence intervals (CI) were calculated using Cox regression.

Results

Dietary riboflavin intake was inversely associated with lung cancer risk (HR?=?0.62; 95?% CI?=?0.43–0.89; p trend?=?0.03 for the highest quartile compared with the lowest). A higher than median intake of methionine was associated with lower risk of lung cancer (HR?=?0.78; 95?% CI?=?0.60–0.99); however, there was no dose–response relation. Intakes of other B vitamins were not associated with lung cancer risk.

Conclusions

Our study suggests that dietary riboflavin intake may be inversely associated with lung cancer risk among female never smokers, which warrants further investigation.     

Diabetes and cancer risk: A Mendelian randomization study

Earlier cohort studies using conventional regression models have consistently shown an increased cancer risk among individuals with type 2 diabetes. However, reverse causality and residual confounding due to common risk factors could exist, and it remains unclear whether diabetes per se contributes to cancer development. Mendelian randomization analyses might clarify the true association between diabetes and cancer risk. We conducted a case–cohort study with 10,536 subcohort subjects and 3,541 newly diagnosed cancer cases derived from 32,949 eligible participants aged 40–69 years within the Japan Public Health Center-based Prospective Study. With 29 known type 2 diabetes susceptibility variants, we used an inverse variance-weighted method to estimate hazard ratios for the associations of diabetes with risks of total and site-specific cancers. The hazard ratios of cancer per doubling of the probability of diabetes were 1.03 (95% confidence interval [CI], 0.92–1.15) overall, 1.08 (95% CI: 0.73–1.59) for the pancreas, 0.80 (95% CI: 0.57–1.14) for the liver and 0.90 (95% CI: 0.74–1.10) for the colorectum. Additional analyses, using publicly available large-scale genome-wide association study data on colorectal cancer in Japan, resulted in a narrower CI (hazard ratio: 1.00; 95% CI: 0.93–1.07). In this prospective Mendelian randomization study with a large number of incident cancer cases, we found no strong evidence to support associations between diabetes and overall and site-specific cancer risks. Our findings suggest that there is little evidence to support the genetic role of type 2 diabetes in cancer development in the Japanese population.     

Prospective study of body size throughout the life‐course and the incidence of endometrial cancer among premenopausal and postmenopausal women

Although adult obesity is known to increase endometrial cancer risk, evidence for childhood obesity is limited. We prospectively examined the association between body fatness throughout life and endometrial cancer risk. 47,289 participants in the Nurses' Health Study (NHS) and 105,386 of the Nurses' Health Study II (NHS II) recalled their body fatness at ages 5, 10 and 20 using a pictogram. Childhood and adolescent body fatness were derived as the average at ages 5 and 10 and ages 10 and 20, respectively. We obtained adult weight from concurrent questionnaires. We calculated hazard ratios (HR) of endometrial cancer using Cox proportional hazards models. During follow‐up, 757 incident cases of endometrial cancer were diagnosed. Body fatness in childhood, at age 10, in adolescence and at age 20 were positively associated with endometrial cancer risk (HR for ≥ Level 5 versus ≤ Level 2 in adolescence: 1.83 (95% CI 1.41–2.37). After adjusting for most recent BMI, none of the associations persisted. Weight change since age 18 was positively associated with endometrial cancer risk [HR for ≥ 25 kg gain versus stable: 2.54 (95% CI 1.80–3.59). Adult BMI was strongly associated with endometrial cancer risk [HR BMI ≥ 35 kg/m² versus BMI ≤ 25 kg/m²: 4.13 (95% CI 3.29–5.16)]. In postmenopausal women, the association with BMI was significantly stronger among non‐users of hormone therapy. In conclusion, obesity throughout life is positively associated with endometrial cancer risk, with adult obesity one of the strongest risk factors. Maintaining a healthy weight throughout life remains important.     

Associations of early life and adulthood adiposity with risk of epithelial ovarian cancer

BackgroundFew studies have evaluated the association between early life adiposity and ovarian cancer risk. Adiposity during different periods of life may be differentially associated with the risk.Patients and methodsWe prospectively followed 133 526 women in the Nurses' Health Study (NHS; 1980–2012) and NHSII (1989–2013). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident ovarian cancer (N = 788) according to validated measures for early life adiposity [body mass index (BMI) at age 10 imputed from somatotype and recalled BMI at age 18) as well as BMI change between age 10 and 18 and after age 18 (current weight assessed on every biennial questionnaire since baseline).ResultsAfter mutual adjustment for BMI at age 10, BMI at age 18 and current BMI, the HR (95% CI) for ovarian cancer risk per 5 kg/m² was 0.84 (0.74–0.96) for BMI at age 10 (P-trend = 0.01), 1.17 (1.03–1.33) for BMI at age 18 (P-trend = 0.02), and 1.06 (0.99–1.14) for current BMI (P-trend = 0.08). However, the inverse association with BMI at age 10 was attenuated after adjusting for BMI change between age 10 and 18 and BMI change after age 18 (HR per 5 kg/m²: 1.04; 95% CI 0.91–1.20; P-trend = 0.55). By contrast, BMI change between age 10 and 18 was strongly positively associated with ovarian cancer risk (HR per 5 kg/m² increase: 1.24; 95% CI 1.11–1.39; P-trend = 0.0002), whereas BMI change since age 18 was only slightly associated with risk (HR per 5 kg/m² increase: 1.06; 95% CI 0.99–1.14; P-trend = 0.10). These associations were in general stronger for premenopausal cases or non-serous tumors.ConclusionEarly life changes in adiposity were more strongly associated with ovarian cancer risk than adulthood changes. The specific mechanisms underlying the associations with adiposity changes during early life warrant further investigation.