Hidemi Ito

Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium

Aims/hypothesisThe aims of the study were to evaluate the association between type 2 diabetes and the risk of death from any cancer and specific cancers in East and South Asians.MethodsPooled analyses were conducted of 19 prospective population-based cohorts included in the Asia Cohort Consortium, comprising data from 658,611 East Asians and 112,686 South Asians. HRs were used to compare individuals with diabetes at baseline with those without diabetes for the risk of death from any cancer and from site-specific cancers, including cancers of the oesophagus, stomach, colorectum, colon, rectum, liver, bile duct, pancreas, lung, breast, endometrium, cervix, ovary, prostate, bladder, kidney and thyroid, as well as lymphoma and leukaemia.ResultsDuring a mean follow-up of 12.7xa0years, 37,343 cancer deaths (36,667 in East Asians and 676 in South Asians) were identified. Baseline diabetes status was statistically significantly associated with an increased risk of death from any cancer (HR 1.26; 95% CI 1.21, 1.31). Significant positive associations with diabetes were observed for cancers of the colorectum (HR 1.41; 95% CI 1.26, 1.57), liver (HR 2.05; 95% CI 1.77, 2.38), bile duct (HR 1.41; 95% CI 1.04, 1.92), gallbladder (HR 1.33; 95% CI 1.10, 1.61), pancreas (HR 1.53; 95% CI 1.32, 1.77), breast (HR 1.72; 95% CI 1.34, 2.19), endometrium (HR 2.73; 95% CI 1.53, 4.85), ovary (HR 1.60; 95% CI 1.06, 2.42), prostate (HR 1.41; 95% CI 1.09, 1.82), kidney (HR 1.84; 95% CI 1.28, 2.64) and thyroid (HR 1.99; 95% CI 1.03, 3.86), as well as lymphoma (HR 1.39; 95% CI 1.04, 1.86). Diabetes was not statistically significantly associated with the risk of death from leukaemia and cancers of the bladder, cervix, oesophagus, stomach and lung.Conclusions/interpretationDiabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality.

Declining trends in prevalence of Helicobacter pylori infection by birth-year in a Japanese population.

Gastric cancer incidence and mortality have been decreasing in Japan. These decreases are likely due to a decrease in prevalence of Helicobacter pylori infection. Our aim was to characterize the trends in prevalence of H. pylori infection focused on birth‐year. We carried out a cross‐sectional study that included 4285 subjects who were born from 1926 to 1989. We defined H. pylori infection by the serum H. pylori antibody titer. Individuals having H. pylori infection and those with negative H. pylori antibody titer and positive pepsinogen test were defined as high‐risk individuals for gastric cancer. We estimated the birth‐year percent change (BPC) of the prevalence by Joinpoint regression analysis. The prevalence of H. pylori infection among the subjects born from 1927 to 1949 decreased from 54.0% to 42.0% with a BPC of −1.2%. It was followed by a rapid decline in those born between 1949 (42.0%) and 1961 (24.0%) with a BPC of −4.5%, which was followed by those born between 1961 (24.0%) and 1988 (14.0%) with a BPC of −2.1%. The proportion of high‐risk individuals for gastric cancer among the subjects born from 1927 to 1942 decreased from 62.0% to 55.0% with a BPC of −0.8%. A subsequent rapid declining trend was observed in those born between 1942 (55.0%) and 1972 (18.0%) with a BPC of −3.6%, and then it became stable. These remarkable declining trends in the prevalence of H. pylori infection by birth‐year would be useful to predict the future trend in gastric cancer incidence in Japan.

Aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) polymorphisms exacerbate bladder cancer risk associated with alcohol drinking: Gene-environment interaction

Although a range of chemical exposures (cigarette smoking and occupational exposure) are recognized risk factors for the development of bladder cancer (BCa), many epidemiological studies have demonstrated that alcohol drinking is not associated with BCa risk. Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms impact the accumulation of acetaldehyde, resulting in an increased risk of various cancers. To date, however, no studies evaluating the association between BCa risk and alcohol drinking have considered these polymorphisms. Here, we conducted a matched case-control study to investigate whether ALDH2 and ADH1B polymorphisms influence BCa risk associated with alcohol drinking. Cases were 74 BCa patients and controls were 740 first-visit outpatients without cancer at Aichi Cancer Center Hospital between January 2001 and December 2005. Odds ratio (OR), 95% confidence interval (CI) and gene-environment interaction were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results showed that ALDH2 Glu/Lys was associated with a significantly increased risk of BCa compared with Glu/Glu (OR 2.03, 95% CI 1.14-3.62, P = 0.017). In contrast, ALDH2 Glu/Lys showed no increase in risk among the stratum of never drinkers compared with Glu/Glu, indicating a gene-environment interaction. ADH1B His/Arg had an OR of 1.98 (1.20-3.24, P = 0.007) compared with His/His. ADH1B Arg+ showed a similar OR and 95% CI. Individuals with ALDH2 Glu/Lys and ADH1B Arg+ had the highest risk of BCa compared with ALDH2 Glu/Glu and ADH1B His/His [OR 4.00 (1.81-8.87), P = 0.001].

Genetic polymorphism of IGF-I predicts recurrence in patients with gastric cancer who have undergone curative gastrectomy

BACKGROUNDnTo our knowledge, no reports have evaluated the effects of genetic polymorphisms of insulin-like growth factor-I (IGF-I) on clinical outcomes of gastric cancer patients.nnnMETHODSnWe retrospectively analyzed the impact of IGF-I polymorphisms on recurrence-free survival (RFS) in 430 patients with gastric cancer who underwent curative gastrectomy between 2001 and 2005 in our institution.nnnRESULTSnAmong the 430 gastric cancer patients, 345 were pathological stage I or II, while 85 were stage III or IV. The median 5-year RFS rate was 85.3% (95% confidence interval [CI] 81.4-88.5). In a multivariate Cox model (adjusted for age, gender, histology, pathological stage, adjuvant chemotherapy, and history of diabetes), two IGF-I polymorphisms, rs1520220 and rs2195239, were significantly associated with RFS (hazard ratio [HR] 0.60, 95% CI 0.40-0.91; and HR 0.60, 95% CI 0.41-0.89, respectively, in a per-allele model). When stratified by stage (I-II versus III-IV), rs1520220 in particular was associated with RFS in patients with stage III-IV disease, with a P-value for interaction of 0.01.nnnCONCLUSIONSnOur findings indicate that genetic polymorphisms of IGF-I may have a substantial effect on recurrence for gastric cancer patients who have undergone curative gastrectomy. This information may help identify population subgroups that could benefit from IGF-I-targeting agents.BACKGROUNDnTo our knowledge, no reports have evaluated the effects of genetic polymorphisms of insulin-like growth factor-I (IGF-I) on clinical outcomes of gastric cancer patients.nnnMETHODSnWe retrospectively analyzed the impact of IGF-I polymorphisms on recurrence-free survival (RFS) in 430 patients with gastric cancer who underwent curative gastrectomy between 2001 and 2005 in our institution.nnnRESULTSnAmong the 430 gastric cancer patients, 345 were pathological stage I or II, while 85 were stage III or IV. The median 5-year RFS rate was 85.3% (95% confidence interval [CI] 81.4-88.5). In a multivariate Cox model (adjusted for age, gender, histology, pathological stage, adjuvant chemotherapy, and history of diabetes), two IGF-I polymorphisms, rs1520220 and rs2195239, were significantly associated with RFS (hazard ratio [HR] 0.60, 95% CI 0.40-0.91; and HR 0.60, 95% CI 0.41-0.89, respectively, in a per-allele model). When stratified by stage (I-II versus III-IV), rs1520220 in particular was associated with RFS in patients with stage III-IV disease, with a P-value for interaction of 0.01.nnnCONCLUSIONSnOur findings indicate that genetic polymorphisms of IGF-I may have a substantial effect on recurrence for gastric cancer patients who have undergone curative gastrectomy. This information may help identify population subgroups that could benefit from IGF-I-targeting agents.

Coffee drinking and colorectal cancer risk: an evaluation based on a systematic review and meta-analysis among the Japanese population

OBJECTIVEnIt remains unclear whether coffee drinking is associated with colorectal cancer risk. We performed a systematic review and meta-analysis of epidemiologic studies on this issue among the Japanese population.nnnMETHODSnOriginal data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. Meta-analysis was performed by using the random effects model to estimate the summary relative risk with 95% confidence interval according to the study design. The final judgment was made based on a consensus of the research group members with consideration for both epidemiological evidence and biological plausibility.nnnRESULTSnWe identified five cohort studies and nine case-control studies. Of these, one cohort study reported a strong inverse association (in women only), whereas three case-control studies reported a strong inverse association with colon or rectal cancer. In meta-analysis, high consumption of coffee was not appreciably associated with colorectal cancer risk among cohort studies, whereas it was associated with significantly lower risk of colorectal or colon cancer among case-control studies. The summary relative risk/odds ratio (95% confidence interval) for the highest versus lowest categories of coffee consumption was 0.95 (0.77-1.17) and 0.78 (0.65-0.95) for cohort and case-control studies, respectively.nnnCONCLUSIONSnThe evidence is insufficient to support that coffee drinking increases or decreases the risk of colorectal cancer among the Japanese population.

Cigarette smoking and the risk of head and neck cancer in the Japanese population: a systematic review and meta-analysis

OBJECTIVEnAlthough cigarette smoking is a well-established risk factor for head and neck cancer, the impact of smoking on head and neck cancer might vary among geographic areas. To date, however, no systematic review of cigarette smoking and head and neck cancer in the Japanese population has yet appeared.nnnMETHODSnWe conducted a systematic review of previous epidemiological studies for cigarette smoking and head and neck cancer among Japanese. Evaluation of associations was based on the strength of evidence (convincing, probable, possible or insufficient) and the magnitude of association (strong, moderate, weak or no association), together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. A meta-analysis was conducted to obtain summary estimates for the overall magnitude of association.nnnRESULTSnWe identified five cohort studies and 12 case-control studies. Four of five cohort studies and 11 of 12 case-control studies showed a strong positive association between cigarette smoking and head and neck cancer. Nine of 12 studies indicated a dose-response relationship between cigarette smoking and the risk of head and neck cancer. Meta-analysis of 12 studies indicated that the summary relative risk for ever smokers relative to never smokers was 2.43 (95% confidence interval: 2.09-2.83). Summary relative risks for current and former smokers relative to never smokers were 2.68 (2.08-3.44) and 1.49 (1.05-2.11), respectively.nnnCONCLUSIONSnCigarette smoking is a convincing risk factor for head and neck cancer in the Japanese population.

Coffee consumption and the risk of colorectal cancer by anatomical subsite in Japan: Results from the HERPACC studies

Consumption of coffee, a popular beverage worldwide, has been associated with lower colorectal cancer (CRC) risk. Although CRC exhibits different biological characteristics by anatomical subsite, the possibly heterogeneous impact of coffee on CRC by anatomical subsite has remained unclear. Here, we conducted two case‐control studies to examine the association between coffee consumption and CRC risk as well as risk by anatomic subsite among Japanese using data from the Hospital‐based Epidemiological Research Program at Aichi Cancer Center I and II (HERPACC‐I and II). Subjects were enrolled in HERPACC‐I between 1988 and 2000 and in HERPACC‐II between 2001 and 2005. Coffee consumption was measured with a self‐administered questionnaire. A conditional logistic regression model was used to calculate odds ratios (ORs) of CRC with coffee consumption, adjusted for potential confounders of age, smoking, alcohol drinking, red meat intake, BMI, exercise, family history of CRC, and diabetes mellitus history. We estimated summary ORs by pooling study‐specific ORs with a fixed effects model. In total, 2,696 CRC cases and 13,480 non‐cancer outpatients as controls were included. Overall, compared to non‐drinkers, ORs of less than 1 cup/day, 1–2 cups/day and 3 or more cups/day for CRC were 0.88 (95% CI: 0.77–1.00), 0.90 (95% CI: 0.80–1.01) and 0.78 (95% CI: 0.65–0.92), respectively (trend‐pu2009=u20090.009). Subsite‐specific analysis revealed a significant inverse linear trend between coffee consumption and distal colon cancer (p‐trendu2009=u20090.048), and a tendency toward a lower risk of rectal cancer (p‐trendu2009=u20090.068). These findings suggest that coffee consumption might impact the prevention of CRC, especially distal colon cancer.

Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five‐year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1‐PRSS2‐rs10273639 and an increased risk of developing PDAC (ORhomozygousu2009=u20091.19, 95% CI 1.02–1.38, pu2009=u20090.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1‐PRSS2‐rs10273639 (ORheterozygousu2009=u20090.51, 95% CI 0.39–0.67, pu2009=u20091.10 × 10−6) and MORC4‐rs 12837024 (ORhomozygousu2009=u20092.07 (1.55–2.77, ptrendu2009=u20090.7 × 10−11). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Coffee drinking and colorectal cancer and its subsites: A pooled analysis of 8 cohort studies in Japan: Coffee and colorectal cancer in Japanese

Coffee is a rich source of bioactive compounds that have potential anticarcinogenic effects. However, it remains unclear whether coffee drinking is associated with colorectal cancer. Also, despite different etiological factors involved in gut physiology, few studies have investigated this association by anatomical site of the lesion. To address these issues, this study examined the association between coffee drinking and colorectal cancer in a pooled analysis from 8 cohort studies conducted in Japan. Among 320,322 participants followed up for 4,503,274 person‐years, 6,711 incident colorectal cancer cases were identified. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using the random effects model. Coffee drinking was not materially associated with colorectal cancer risk in men or women (pooled HR 0.92, 95% CI 0.82–1.03 in men and pooled HR 0.90, 95% CI 0.76–1.07 in women). Analysis by subsite showed a lower risk of colon cancer among female drinkers of ≥3 cups coffee/day (pooled HR 0.80, 95% CI 0.64–0.99). There was no such association in men. Coffee drinking was not associated with risk of rectal cancer in men or women. Results were virtually the same among never smokers except for an increased risk of rectal cancer associated with frequent coffee consumption. Coffee drinking may be associated with lower risk of colon cancer in Japanese women.

Rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk

NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 Gu2009>u2009C, located in a microRNA binding site in the 3′-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (ORu2009=u20091.214, 95% CIu2009=u20090.936–1.574, Pu2009=u20090.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2u2009>u20090.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (ORu2009=u20091.014, 95% CIu2009=u20090.969–1.060, Pu2009=u20090.556) nor in Asian women (ORu2009=u20090.998, 95% CIu2009=u20090.905–1.100, Pu2009=u20090.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.