Lumen Loss at 1 Year After Bare Nitinol Stent Implantation in the Superficial Femoral Artery.

PURPOSE: To investigate lumen loss (LL) at 1 year after bare nitinol stent (BNS) implantation for de novo superficial femoral artery (SFA) lesions. MATERIALS AND METHODS: The subjects were 701 consecutive patients (mean age 74±9 years; 492 men) with 817 de novo SFA lesions treated with BNS implantation between January 2004 and September 2015. The mean lesion length was 141±88 mm and the mean vessel diameter was 5.4±0.9 mm. The endpoint was LL at 1 year after BNS implantation. Secondary outcomes were restenosis and target lesion revascularization (TLR) estimated using the Kaplan-Meier method; estimates are reported with the 95% confidence interval (CI). LL was defined as the minimum lumen diameter immediately after BNS implantation minus that at 1 year measured by angiographic quantitative vessel analysis. The distribution of LL in the overall population was estimated using an accelerated failure time model. RESULTS: Mean LL at 1 year was estimated to be 1.74±1.28 mm (95% CI 1.63 to 1.84). Current smoking was positively associated with LL (p=0.015), whereas lack of cilostazol use was correlated with an increase in LL (p=0.001). Reference vessel diameter and lesion length did not have any significant association with LL at 1 year. The 1-year cumulative estimate of restenosis was 25% (95% CI 22% to 28%); the corresponding value for TLR was 18% (95% CI 15% to 21%). CONCLUSION: Mean LL progressed by at least 1.6 mm up to 1 year after BNS implantation. The risk factors for increased LL were current smoker and lack of cilostazol use.

Structural and Functional Basis for LILRB Immune Checkpoint Receptor Recognition of HLA-G Isoforms.

Human leukocyte Ig-like receptors (LILR) LILRB1 and LILRB2 are immune checkpoint receptors that regulate a wide range of physiological responses by binding to diverse ligands, including HLA-G. HLA-G is exclusively expressed in the placenta, some immunoregulatory cells, and tumors and has several unique isoforms. However, the recognition of HLA-G isoforms by LILRs is poorly understood. In this study, we characterized LILR binding to the ß2-microglobulin (ß2m)-free HLA-G1 isoform, which is synthesized by placental trophoblast cells and tends to dimerize and multimerize. The multimerized ß2m-free HLA-G1 dimer lacked detectable affinity for LILRB1, but bound strongly to LILRB2. We also determined the crystal structure of the LILRB1 and HLA-G1 complex, which adopted the typical structure of a classical HLA class I complex. LILRB1 exhibits flexible binding modes with the α3 domain, but maintains tight contacts with ß2m, thus accounting for ß2m-dependent binding. Notably, both LILRB1 and B2 are oriented at suitable angles to permit efficient signaling upon complex formation with HLA-G1 dimers. These structural and functional features of ligand recognition by LILRs provide novel insights into their important roles in the biological regulations.

Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction.

BACKGROUND: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. RESULTS: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). CONCLUSIONS: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

Preparation and Evaluation of Stomatitis Film Using Xyloglucan Containing Loperamide.

Stomatitis induced by radiation therapy or cancer chemotherapy is a factor in sleep disorders and/or eating disorders, markedly decreasing patient quality of life. In recent years, disintegrating oral films that are easy to handle have been developed; therefore, we focused on the formulation of these films. We prepared an adhesive film for the oral cavity using xyloglucan (Xylo), which is a water-soluble macromolecule. We used loperamide, which has been reported to relieve pain caused by stomatitis effectively, as a model drug in this study. Films were prepared from Xylo solutions (3% (w/w)) and hypromellose (HPMC) solutions (1% (w/w)). Xylo and HPMC solutions were mixed at ratios of 1 : 1, 2 : 1, or 3 : 1 for each film, and films 2×2 cm weighing 3 g were prepared and dried at 37°C for 24 h. Physicochemical properties such as strength, adhesiveness, disintegration behavior, and dissolution of loperamide from films were evaluated. Films prepared from Xylo solution alone had sufficient strength and mucosal adhesion. On the other hand, films prepared from a mixture of Xylo and HPMC were inferior to those made from Xylo, but showed sufficient strength and mucosal adhesion and were flexible and easy to handle. The films prepared in this study are useful as adhesion films in the oral cavity.

Polymorphisms in base excision repair genes are associated with endometrial cancer risk among postmenopausal Japanese women.

OBJECTIVES: Polymorphisms in base excision repair (BER) genes are associated with risk for several types of cancers but have not been studied with respect to endometrial cancer among Japanese women. Therefore, we conducted a case-control study to explore the association between polymorphisms in BER genes and the risk for endometrial cancer. METHODS/MATERIALS: This study included a total of 91 postmenopausal subjects with endometrial cancer and 261 controls without cancer who visited the Aichi Cancer Center between 2001 and 2005. We focused on single nucleotide polymorphisms within coding regions of 5 BER genes (OGG1, MUTYH, XRCC1, APEX1, and PARP1). To assess lifestyle in the etiology of endometrial cancer, we used a self-administered questionnaire. Associations were evaluated using multivariate unconditional logistic regression models. We also assessed whether there were intergenic associations or an interaction with obesity. RESULTS: We observed a significant association between endometrial cancer risk and XRCC1 rs1799782 (C > T, Arg194Trp) and XRCC1 rs25487 (G > A, Arg399Gln). We uncovered a significant association between obesity (body mass index, ≥ 25) and rs25487. The XRCC1 polymorphisms were in complete linkage disequilibrium, and the XRCC1 haplotype TG associated significantly with endometrial cancer risk. The interaction between the CA haplotype and body mass index was marginally significant, whereas interaction between haplotype in XRCC1 and rs1136410 (PARP1) was not significant. CONCLUSIONS: We found a significant association between endometrial cancer risk and XRCC1 polymorphisms and haplotype TG in postmenopausal Japanese women.

Alcohol and dietary folate intake and the risk of breast cancer: a case-control study in Japan.

Owing to its interaction with alcohol, folate has been suggested to be a potential factor for many types of cancer. The impact of these factors on the risk of breast cancer among Asian populations has not been fully examined, however, particularly with respect to receptor status. We carried out a case-control study in premenopausal and postmenopausal Japanese women, including 1754 breast cancer patients and 3508 noncancer controls. We determined the association between self-reported alcohol drinking, dietary folate intake, and the risk of breast cancer. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic models adjusted for potential confounders. Alcohol consumption was associated with the risk of breast cancer, with the OR for a drinker consuming 23 g or more per day relative to a nondrinker of 1.39 (95% CI: 1.07-1.80). A significant inverse association was observed between folate intake and overall risk of breast cancer, with an OR of 0.79 (95% CI: 0.68-0.93; Ptrend=0.004) for the highest tertile relative to the lowest. The OR of a drinker consuming 23 g or more per day relative to a nondrinker with a low folate intake was 1.58 (95% CI: 1.06-2.33). However, a significantly increased risk was not observed in tertile 2 and tertile 3 folate in taker with any amount of alcohol consumption. Higher folate intake decreases the risk of breast cancer among Japanese, whereas alcohol intake increases the risk. These two factors interact with each other, and the excess risk of breast cancer with alcohol consumption might be attenuated by increasing the intake of folate. In addition, the effects of folate/alcohol may vary according to the tumor subtype.

Differential impact of body mass index and its change on the risk of breast cancer by molecular subtype: A case-control study in Japanese women.

UNLABELLED: Body mass index (BMI) is an independent risk factor for luminal-type breast cancer in Western populations. However, it is unclear whether the impact of BMI differs according to breast cancer subtype in Japanese populations. We conducted a case-control study with 715 cases and 1430 age- and menopausal status-matched controls to evaluate the associations of BMI and its change (from age 20 years to the current age) with breast cancer risk. We applied conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Tumor subtypes were divided into four subtypes, namely the luminal, luminal/HER2, HER2-rich, and triple-negative subtypes. Current BMI and BMI change were positively associated with postmenopausal breast cancer risk. On stratified analysis by tumor subtype, we observed associations between current BMI and BMI change and postmenopausal breast cancer risk for the luminal subtype, with OR for each 1 kg/m(2) increase in current BMI of 1.14 (95% CI: 1.07 - 1.20) and the corresponding OR of BMI change of 1.16 (1.09 - 1.23) (each P(trend) < 0.001). Additionally, we found the same tendency for the triple-negative subtype, with the OR for a 1 kg/m(2) increase in current BMI of 1.21 (1.05 - 1.39) and that for BMI change of 1.18 (1.02 - 1.36) (P(trend) was 0.008 and 0.024, respectively). In premenopausal women, a suggestive inverse association was observed between BMI change and breast cancer risk for the luminal subtype only, with OR of BMI change of 0.93 (0.87 - 1.00, P(trend) = 0.054). No association was seen between BMI at age 20 years and risk of any tumor subtype. In conclusion, BMI and its change are associated with the risk of both luminal and triple-negative breast cancer among postmenopausal Japanese women. These findings suggest the etiological heterogeneity of breast cancer among tumor subtypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-1-39) contains supplementary material, which is available to authorized users.

A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population.

Genome-wide association studies (GWASs) have identified genetic variants associated with breast cancer. Most GWASs to date have been conducted in women of European descent, however, and the contribution of these variants as predictors in Japanese women is unknown. Here, we analyzed 23 genetic variants identified in previous GWASs and conducted a case-control study with 697 case subjects and 1,394 age- and menopausal status-matched controls. We fit conditional regression models with genetic variants and conventional risk factors. In addition, we created a polygenetic risk score, using those variants with a statistically significant association with breast cancer risk, and also evaluated the contribution of these genetic predictors using the c statistic. Eleven single-nucleotide polymorphisms (SNPs) revealed significant associations with breast cancer risk. A dose-dependent association was observed between the risk of breast cancer and the genetic risk score, which was an aggregate measure of alleles in seven selected variants, namely FGFR2-rs2981579, TOX3/TNRC9-rs3803662, C6orf97-rs2046210, 8q24-rs13281615, SLC4A7-rs4973768, LSP1-rs38137198, and CASP8-rs10931936. Compared to women with scores of 3 or less, odds ratios (ORs) for women with scores of 4-5, 6-7, 8-9, and 10 or more were 1.33 (95% confidence interval, 1.00-1.80), 1.71 (1.26-2.30), 3.01 (1.97-4.58), and 8.69 (2.75-27.5), respectively (P (trend) = 1.9 × 10(-9)). The c statistic for a model including the genetic risk score in addition to the conventional risk factors was 0.6933, versus 0.6652 with the conventional risk factors only (P = 1.3 × 10(-4)). Population-attributable fraction of the risk score was 33.0%. In conclusion, we identified a genetic risk predictor of breast cancer in a Japanese population. Risk models which include a genetic risk score are possibly useful in distinguishing women at high risk of breast cancer from those at low risk, particularly in the context of targeted prevention.

Weight gain during adulthood and body weight at age 20 are associated with the risk of endometrial cancer in Japanese women.

BACKGROUND: Current obesity is an established risk factor for endometrial cancer; however, the roles of weight gain during adulthood and obesity in early adulthood on endometrial cancer have not been elucidated. Here, we conducted a case-control study comprising 222 histologically diagnosed incident endometrial cancer cases and 2162 age- and menstrual-status matched non-cancer controls. METHODS: Information on current body weight, weight and height at age 20 years, and lifestyle/environmental factors was obtained from a self-administered questionnaire. Subjects were classified into 3 groups according to change in body mass index (BMI, kg/m(2)) from age 20 years to enrollment (≤0 [reference], 0-3, and >3 kg/m(2)). The effects of adult BMI change and obesity in early adulthood were evaluated using an unconditional logistic regression model adjusted for potential confounders. RESULTS: A high BMI at age 20 (BMI ≥25, BMI <25 as reference) was significantly positively associated with endometrial cancer risk (P = 0.005), as was a BMI increase during adulthood (0-3 BMI change, multivariate odds ratio [OR] = 1.28, 95% confidence interval [CI] = 0.88-1.87; >3 BMI change, OR = 2.02, 95% CI = 1.38-2.96; P-trend < 0.001). Parity and BMI at age 20 appeared to modify the effect of weight gain on cancer risk, albeit without statistical significance. This positive association of weight gain with risk was observed only for endometrioid adenocarcinoma. CONCLUSIONS: The results show that endometrial cancer is positively associated with obesity at age 20 and weight gain during adulthood among Japanese women.

Interaction between CYP19A1 polymorphisms and body mass index in the risk of endometrial cancer in postmenopausal Japanese women.

Extra-ovarian sex hormone production plays an important role in endometrial cancer in postmenopausal women. Aromatase, which is encoded by CYP19A1, is a key enzyme in estrogen biosynthesis after menopause. To examine the association between polymorphisms in CYP19A1 and endometrial cancer risk among postmenopausal Japanese women, we conducted a hospital-based case control study in 48 patients with histologically diagnosed incident endometrial cancer and 253 non-cancer control subjects. Information on lifestyle factors was obtained from a self-administered questionnaire. Twenty-five tag SNPs (single nucleotide polymorphisms) of CYP19A1 were examined by TaqMan methods and haplotype blocks were identified by LD analysis. Associations were assessed by an unconditional logistic regression model adjusted for potential confounders. We found no significant association between CYP19A1 genotypes and haplotypes and endometrial cancer risk. However, among women with a BMI (body mass index) >23, significantly positive associations were observed for rs2899473, rs1865803, rs16964220, rs2008691, rs17647707, rs17647719, rs1902586, rs936306, and rs1004982, while negative associations were seen for rs1902585, rs752760 and rs2445768. These showed significant interactions with BMI. Further, of the six haplotype blocks identified, the haplotype CTT of block 1, GATA of block 5 and CA of block 6 showed statistically significant interactions with BMI. These results suggest that CYP19A1 polymorphisms might play an important role in the etiology of endometrial cancer, and that the effect of these polymorphisms might be influenced by BMI.

HLA-A alleles and the risk of cervical squamous cell carcinoma in Japanese women.

BACKGROUND: We conducted a case-control study to examine the relationship between human leukocyte antigen-A (HLA-A) allele polymorphism and the pathogenesis of cervical neoplasia among Japanese women. METHODS: A total of 119 patients with invasive cervical squamous cell carcinoma were compared to 119 age- and menopausal status-matched non-cancer controls. Blood samples were taken from all cases and controls and lifestyle information was collected by means of a self-administered questionnaire. The estimated impact of HLA-A alleles on cervical cancer risk was evaluated by unconditional logistic regression models. RESULTS: The frequency of HLA-A(*)0206 among cases was significantly lower than among controls (P = 0.006). There was an inverse association between A(*)0206 and cervical cancer risk (odds ratio [OR] = 0.31, 95% confidence interval [95% CI] = 0.15 to 0.65, P = 0.002), and a positive association for HLA-A(*)2402 (OR = 1.76, 95% CI = 1.00 to 3.09, P = 0.048). After correction for multiple comparisons, A(*)0206 was significantly associated with reduced cervical cancer risk (corrected P = 0.036). Furthermore, the inverse association between A(*)0206 and cervical cancer risk was independent of smoking status (never smoker: OR = 0.37, 95% CI = 0.15 to 0.90; ever smoker: OR = 0.23, 95% CI = 0.06 to 0.89). CONCLUSIONS: There was an inverse association between HLA-A(*)0206 and cervical cancer risk among Japanese women, which suggests that HLA-A polymorphism influences cervical cancer risk. Further investigation in other populations is thus warranted.

Association between vitamin D and calcium intake and breast cancer risk according to menopausal status and receptor status in Japan.

Although several studies have investigated the possible association between elevated vitamin D and calcium intake and low breast cancer risk, findings have been inconsistent. We conducted a case-control study to clarify the association between vitamin D and calcium intake and breast cancer risk among pre- and post- menopausal women in Japan. We also investigated whether these effects were modified by tumor receptor status, specifically estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor-2 (HER2) status. We examined 1803 breast cancer patients and 3606 age- and menopausal status-matched noncancer controls. Among cases, 713 were assessed for ER, PR, and HER2 status. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional or unconditional logistic models adjusted for potential confounders. A significant inverse association was observed between vitamin D and calcium intake and breast cancer risk among all subjects, with top quartile ORs of 0.76 (95% CI, 0.63-0.90; trend P = 0.001) and 0.83 (95% CI, 0.69-0.99; trend P = 0.038), respectively. In analyses stratified by menopausal status, a significant association between risk and vitamin D was observed only among premenopausal women (trend P < 0.001), whereas that between risk and calcium intake was seen only among postmenopausal women (trend P = 0.022). Heterogeneity by menopausal status for these associations was statistically significant. This association was modified by tumor receptor status. These findings suggest that the protective effects of vitamin D and calcium intake against breast cancer risk may differ by menopausal status and receptor status.

Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women.

In postmenopausal women, extraovarian sex hormone production plays an important role in hormone-related diseases, such as breast and endometrial cancers. Aromatase, an enzyme encoded by CYP19A1, is a key enzyme involved in estrogen biosynthesis. The impact of CYP19A1 polymorphisms on serum sex hormone levels in the Japanese population has never been investigated. This study enrolled 100 postmenopausal Japanese women found to be without cancer. Twenty-five CYP19A1 loci were identified, and measurements were conducted on serum levels of sex hormones; lifestyle data were collected, namely estrone (E1), estradiol (E2), testosterone and sex hormone-binding globulin (SHBG). We conducted a cross-sectional analysis to evaluate the impact of CYP19A1 haplotype on serum sex hormone levels. We found that subjects with BMI>or=25 kg/m(2) showed a significant difference in circulating testosterone levels (0.29+/-0.19, P=0.050). Neither age nor the amount of physical exercise or drinking habits showed any effect on hormone levels. We identified seven haplotype blocks in CYP19A1 by LD analysis. Estrone levels differed in rs12148604 (SNP 1) and rs11632903 (SNP14). No significant locus for estradiol was observed. SHBG levels were associated with rs4441215 (SNP11). Testosterone levels were strongly associated with rs752760 (SNP24) and rs2445768 (SNP25) and weakly associated with SNP 1, SNP11 and SNP14 as well. We found that polymorphisms in CYP19A1 influence sex hormone levels in Japanese postmenopausal women.

Effect of soybean on breast cancer according to receptor status: a case-control study in Japan.

The possible association of high soy food consumption with low incidence of breast cancer in Asian countries has been widely investigated, but findings from epidemiologic studies have been inconsistent. Breast cancers defined by receptor status, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) may have distinct etiologic factors. Here, we conducted a case-control study to clarify associations between intake of soybean products and breast cancer risk according to receptor status. A total of 678 breast cancer cases and 3,390 age- and menopausal status-matched noncancer controls were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders. On analysis according to receptor status, we observed a significantly reduced risk of ER-positive (ER+) (top tertile OR = 0.74; 95% CI, 0.58-0.94; trend p = 0.01) and HER2-negative (HER2-) tumors (top tertile OR = 0.78; 95% CI, 0.61-0.99; trend p = 0.04). Further, when the 3 receptors were jointly examined, a reduced risk was observed only in patients with ER+/PR+/HER2- tumor (top tertile OR = 0.73; 95% CI, 0.54-0.97; trend p = 0.03). These findings indicate that the protective effect of soy against breast cancer risk differs by receptor status.

Soy consumption reduces the risk of non-small-cell lung cancers with epidermal growth factor receptor mutations among Japanese.

Epidermal growth factor receptor (EGFR) mutations play substantial roles in genesis and proliferation of non-small-cell lung cancers (NSCLCs). We recently found that reproductive factors have a substantial impact on risk of development of NSCLCs featuring such EGFR mutations. Therefore, we explored the influence of dietary habits on NSCLC risk with reference to the EGFR mutational status. We conducted a case-control study using 353 patients with NSCLCs (122 EGFR mutated and 231 EGFR wild-type) and 1765 age-sex matched non-cancer control subjects. Dietary exposure was based on a semiquantitative food frequency questionnaire and impact of major food items, like meats, seafoods, vegetables and soybean products was assessed by multivariate logistic regression. Soybean products demonstrated a protective association with EGFR mutated, but not EGFR wild-type NSCLCs, with multivariate-adjusted odds ratios and 95% confidence intervals for the 2nd and 3rd tertile of soybean product consumption of 0.79 (0.50-1.27) and 0.56 (0.34-0.93) relative to those in the lowest tertile (trend P = 0.023). In conclusion, soy consumption may exert a protective association against the development of NSCLCs with EGFR mutations, providing possible insights into mechanisms of their genesis.

Reduced risk of endometrial cancer from alcohol drinking in Japanese.

The role of alcohol consumption in the etiology of endometrial cancer has not been clarified. To examine the association between alcohol consumption and endometrial cancer risk, we conducted a case-control study with 148 histologically diagnosed incident endometrial cancer cases and 1468 matched non-cancer controls. Median consumption of alcohol was only 19.3 g/week among cases who drank and 28.2 g/week among controls who drank. These values are lower than in Western countries. Relative risk was analyzed in subjects classified into four groups according to weekly alcohol consumption (non-drinkers, 1-24 g/week, 25-175 g/week, and >175 g/week). Confounder-adjusted odds ratios for those consuming alcohol at <25 g/week, 25-175 g/week, and >175 g/week compared to non-drinkers were 0.79 (95% confidence interval (CI), 0.49-1.28), 0.42 (95% CI, 0.23-0.79), and 0.47 (95% CI, 0.14-1.58), respectively. Further analysis was conducted concerning self-reported physical reaction to alcohol. Among women without flushing after drinking, a significant inverse association between risk and alcohol intake was seen (trend P = 0.001). In contrast, no protective effect of alcohol was seen among women who experience flushing after drinking. These results suggest the presence of an inverse association between alcohol drinking and endometrial cancer risk among Japanese women, and that this association is evident among those without flushing. Further investigation of these findings is warranted.

One-carbon metabolism-related gene polymorphisms and risk of breast cancer.

Environmental exposures and/or genetic background in Japanese population, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Folate plays an essential role in DNA methylation and synthesis, and thus may be involved in the development of breast cancer. Functional polymorphisms in genes encoding one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G) and thymidylate synthase (TS), influence folate metabolism, but epidemiological studies have yielded inconsistent findings. We therefore conducted a case-control study to clarify their associations with breast cancer risk. A total of 456 breast cancer cases and 912 age-matched and menopausal status-matched non-cancer controls were genotyped for the polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic models adjusted for potential confounders and gene-environment interactions between the polymorphisms and folate consumption were also evaluated. We observed an increased risk of postmenopausal breast cancer with the MTHFR 677TT genotype (OR = 1.83, 95% CI: 1.08-3.11) with a menopausal status-based analysis. In combination analysis, a significantly elevated OR was found among postmenopausal women with the MTHFR 677TT genotype and lower intake of dietary folate compared with those with 677CC genotype and adequate folate consumption (OR = 2.80, 95% CI: 1.11-7.07). In addition, interaction between the MTRR A66G polymorphism and folate intake for risk of postmenopausal breast cancer was observed (interaction P = 0.008). Our findings indicated that the MTHFR and MTRR polymorphisms were associated with individual susceptibility to breast cancer among postmenopausal women.

Dietary patterns and the risk of breast cancer in Japanese women.

Components of the Japanese diet that might contribute to the relatively low breast cancer incidence in Japanese women have not been clarified in detail. To evaluate associations between broad dietary patterns and breast cancer risk in a Japanese population, the authors conducted a case-control study using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). Factor analysis (principal components) was used to derive food patterns based on the 31 food variables and allowed designation of four major dietary patterns: prudent, fatty, Japanese and salty. In total, 1885 breast cancer cases were included and 22,333 female non-cancer patients were recruited as the control group. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined using multiple logistic regression analysis. After adjusting for potential confounders, there were no clear associations between the fatty, Japanese or salty dietary patterns and overall breast cancer risk. In contrast, an inverse association was evident for the prudent dietary. Women in the highest quartile of the prudent dietary pattern scores, had a 27% decreased risk of breast cancer compared with those in the lowest (95% CI: 0.63-0.84, p for trend < 0.0001). In addition, for women with a body mass index > or = 25, the highest quartile of the fatty factor score was associated with a 58% increment in breast cancer risk compared to the lowest quartile, with a significant linear trend (P = 0.027). The authors found the prudent dietary pattern to be negatively associated with breast cancer risk. In addition, the fatty and Japanese patterns may increase breast cancer risk among obese women.