Interaction between cytochrome P450 gene polymorphisms and serum organochlorine TEQ levels in the risk of endometriosis

Exposure to dioxins and polychlorinated biphenyls (PCBs) has been suggested as a possible etiologic factor for endometriosis, but the association remains highly controversial. To assess whether cytochrome P450 (CYP) gene polymorphisms modulate the effect of dioxins and/or PCBs in endometriosis risk, we conducted a case-control study among infertile Japanese women. A total of 138 eligible women aged 20-45 were diagnosed laparoscopically and classified into three subgroups: control (no endometriosis), early endometriosis (stages I-II) and advanced endometriosis (stages III-IV). Neither CYP1A1 Ile462Val and CYP1B1 Leu432Val polymorphisms (genotypes with versus genotypes without the minor allele) nor serum dioxin and PCB toxic equivalency (TEQ) levels (low versus high) were independently associated with either early or advanced endometriosis risk. However, genotypes with the CYP1A1 462Val allele showed a statistically significant reduced risk of advanced endometriosis in combination with high serum dioxin TEQ levels (adjusted odds ratio = 0.13, 95% confidence interval: 0.02-0.76) (P for interaction = 0.08). Although no association was found between serum PCB TEQ level and advanced endometriosis in any stratum of CYP1B1 Leu432Val polymorphism, a statistically significant interaction was found (P for interaction = 0.05). CYP1A1 and CYP1B1 polymorphisms may modify the relation between environmental exposure to organochlorine and advanced endometriosis risk.     

Prospective study showing that dietary vitamin C reduced the risk of age-related cataracts in a middle-aged Japanese population

Background In Western countries, many epidemiological studies have demonstrated that specific dietary nutrients are associated with the risk of developing age-related cataracts. These reports have suggested that dietary antioxidant vitamins, in particular vitamin C, can play a role in preventing the onset or progression of age-related visual impairment. However, few prospective studies have examined this relationship in a general Asian population. Therefore, in this study, we investigated whether dietary vitamin C was associated with a lower incidence of age-related cataracts by performing a 5-year prospective population-based analysis using data from a cohort of over 30,000 Japanese residents recruited to the Japan Public Health Center-based Prospective Study (JPHC Study) cohort I. Aim of the study We carried out a prospective analysis of the association between vitamin C intake and age-related cataracts among middle-aged Japanese, to study the effects of dietary antioxidants in an Asian population. Methods This 5-year population-based study included 16,415 men and 18,771 women (aged 45–64 years), who were recruited onto the JPHC Study and had not reported cataracts in baseline surveys. Vitamin C was calculated from the nutrient intake assessed by self-administered food-frequency questionnaires (FFQ). Self-reported questionnaires were used to assess two endpoints: diagnosis or extraction of cataracts. Results At follow-up, 216 men and 551 women reported new diagnoses, and 110 men and 187 women reported extractions of cataracts. For both endpoints, a higher vitamin C intake was associated with a reduced incidence of cataracts in both sexes. After adjusting for potential confounding factors, the multivariate odds ratios (ORs) for men and women in the highest quintiles of energy-adjusted vitamin C intake, relative to the lowest quintiles, were 0.65 (95% CI, 0.42–0.97) and 0.59 (95% CI, 0.43–0.89) for cataract diagnoses, and 0.70 (95% CI, 0.44–1.20) and 0.64 (95% CI, 0.41–0.94) for cataract extractions, respectively. Conclusions Dietary vitamin C intake might lower the risk of age-related cataracts among middle-aged Japanese. Study Group Members: Members of the Japan Public Health Center-based Prospective Study Group are: S. Tsugane, M. Inoue, T. Sobue, T. Hanaoka, National Cancer Center, Tokyo; J. Ogata, S. Baba, T. Mannami, A. Okayama, National Cardiovascular Center, Suita; K. Miyakawa, F. Saito, A. Koizumi, Y. Sano, I. Hashimoto, Iwate Prefectural Ninohe Public Health Center, Ninohe; Y. Miyajima, N. Suzuki, S. Nagasawa, Y. Furusugi, Akita Prefectural Yokote Public Health Center, Yokote; H. Sanada, Y. Hatayama, F. Kobayashi, H. Uchino, Y. Shirai, T. Kondo, R. Sasaki, Y. Watanabe, Y. Miyagawa, Nagano Prefectural Saku Public Health Center, Saku; Y. Kishimoto, E. Takara, T. Fukuyama, M. Kinjo, M. Irei, H. Sakiyama, Okinawa Prefectural Chubu Public Health Center, Okinawa; K. Imoto, H. Yazawa, T. Seo, A. Seiko, F. Ito, F. Shoji, Katsushika Public Health Center, Tokyo; A. Murata, K. Minato, K. Motegi, T. Fujieda, Ibaraki Prefectural Mito Public Health Center, Mito; K. Matsui, T. Abe, M. Katagiri, M. Suzuki, Niigata Prefectural Kashiwazki and Nagaoka Public Health Center, Kashiwazaki and Nagaoka; M. Doi, A. Terao, Y. Ishikawa, Kochi Prefectural Chuo-higashi Public Health Center, Tosayamada; H. Sueta, H. Doi, M. Urata, N. Okamoto, F. Ide, Nagasaki Prefectural Kamigoto Public Health Center, Arikawa; H. Sakiyama, N. Onga, H. Takaesu, Okinawa Prefectural Miyako Public Health Center, Hirara; F. Horii, I. Asano, H. Yamaguchi, K. Aoki, S. Maruyama, M. Ichii, Osaka Prefectural Suita Public Health Center, Suita; S. Matsushima, S. Natsukawa, Saku General Hospital, Usuda; M. Akabane, Tokyo University of Agriculture, Tokyo; M. Konishi, K. Okada, Ehime University, Matsuyama; H. Iso, Y. Honda, Tsukuba University, Tsukuba; H. Sugimura, Hamamatsu University, Hamamatsu; Y. Tsubono, Tohoku University, Sendai; M. Kabuto, National Institute for Environmental Studies, Tsukuba; S. Tominaga, Aichi Cancer Center Research Institute, Nagoya; M. Iida, W. Ajiki, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka; S. Sato, Osaka Medical Center for Health Science and Promotion, Osaka; N. Yasuda, Kochi Medical School, Nankoku; S. Kono, Kyushu University, Fukuoka; K. Suzuki, Research Institute for Brain and Blood Vessels Akita, Akita; Y. Takashima, Kyorin University, Mitaka; E. Maruyama, Kobe University, Kobe; the late M. Yamaguchi, Y. Matsumura, S. Sasaki, S. Watanabe, National Institute of Health and Nutrition, Tokyo; and T. Kadowaki, Tokyo University, Tokyo.     

Eribulin-based neoadjuvant chemotherapy for triple-negative breast cancer patients stratified by homologous recombination deficiency status: a multicenter randomized phase II clinical trial

Breast Cancer Research and Treatment - To investigate clinical usefulness of eribulin-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Patients in group A...     

Long-term antihypertensive drug use and risk of cancer: The Japan Public Health Center-based prospective study

Antihypertensive drugs have been reported as both promotors and suppressors of cancers and this relationship has been known for several decades. We examined a large-scale prospective cohort study in Japan to assess the relationship between long-term antihypertensive drug use, for 10 y, and carcinogenesis. We divided participants into 4 categories according to the period of antihypertensive drug use, and calculated the hazard ratios (HRs), 95% confidence intervals (CIs), and P trends using the Cox proportional hazard model. In all cancers, there was a significant difference in the medication period and the adjusted HR, as well as a significant difference in the P trend. Furthermore, more than 10 y use of antihypertensive drugs significantly increased the adjusted HR in colorectal cancer (multivariable HR: 1.18, 95% CI: 1.01-1.37 in the >10 y use group; P for trend = .033) and renal cancer (multivariable HR: 3.76, 95% CI: 2.32-6.10 in the 5-10 y use group; multivariable HR: 2.14, 95% CI: 1.29-3.56 in the >10 y use group; P for trend < .001). The highest adjusted HR in renal cancer among antihypertensive drug users was observed in the analysis performed on patients in which the outcomes were calculated from 3 y after the 10-y follow-up survey and by sex. A large-scale cohort study in Japan suggested that long-term use of antihypertensive drugs may be associated with an increased incidence of colorectal and renal cancer.     

Ultrasonographically assessed carotid atherosclerosis in Japanese type 2 diabetic patients: Role of nonesterified fatty acids

The aim of the present study was to evaluate the association of carotid atherosclerosis (intimal-medial thickness [IMT] in plaque-free segments and carotid stenosis in plaque segments) with serum nonesterified fatty acids (NEFA) in diabetic and nondiabetic patients. Fifty-one nonobese nonhypertensive Japanese type 2 diabetic patients aged 38 to 83 years (60.0 +/- 1.5 years, mean +/- SEM) and 23 age-matched (60.4 +/- 2.2 years, P =.439; range, 36 to 74 years) and sex-matched nondiabetic subjects were examined. The duration of diabetes was 9.6 +/- 1.0 years. Body mass index (BMI), blood pressure (systolic pressure, diastolic pressure), glycosylated hemoglobin (HbA(1c)), and fasting concentrations of plasma glucose, serum lipids (triglycerides, total, and high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol) and serum NEFA were measured. Using high-resolution B-mode ultrasound scan, we measured IMT in plaque-free segments of bilateral common carotid arteries, and the mean of IMT in 2 vessels was used for the analysis. Furthermore, we calculated the degree of stenosis in plaque segments of bilateral common carotid arteries. The degree of carotid stenosis was expressed as a percentage ratio between the area of plaque and that of the lumen using the formula (Lumen Area - Residual Lumen) x 100. Both the areas were automatically measured by the system on a frozen transverse scanning plane at the site of maximal narrowing. When 2 or more plaques were present in the vessel, only that causing the greatest degree of stenosis was considered for analysis. Univariate regression analyses showed that mean IMT in plaque-free segments was positively correlated with age (r =.498, P =.0004) and NEFA (r =.354, P =.0188) in type 2 diabetic patients. The degree of stenosis was positively correlated to age (r =.422, P =.0028), duration of diabetes (r =.313, P =.0268) and NEFA (r =.540, P =.0003) in diabetic patients. Other variables, including BMI and lipid profile, were not associated both with mean IMT in plaque-free segments and the degree of stenosis in plaque segments in our diabetic patients. Multiple regression analyses showed that mean IMT in plaque-free segments was independently associated with age (P =.0003, F = 15.2), which explained 26.1% of the variability of IMT in our diabetic patients. The degree of stenosis was independently predicted by NEFA (P =.0047, F = 8.9), which explained 17.2% of the variability of the carotid stenosis in our diabetic patients. In contrast, mean IMT in plaque-free segments was positively correlated to age in nondiabetic subjects (r =.450, P =.0347). There was, however, no relationship between the degree of stenosis and the variables, including age and NEFA, in nondiabetic subjects. These results indicate that the factors contributing to IMT in plaque-free segments and the degree of carotid stenosis in plaque segments are different in nonobese nonhypertensive Japanese type 2 diabetic patients. IMT in plaque-free segments was independently associated with age both in nondiabetic and diabetic subjects, whereas the serum NEFA level independently predicted the degree of stenosis in plaque segments in our diabetic patients, while not in nondiabetic subjects. Thus, NEFA is considered to be one of the new risk factors responsible for the progression of carotid atherosclerosis in nonobese nonhypertensive Japanese type 2 diabetic patients.     

Fish,n − 3 polyunsaturated fatty acids and n − 6 polyunsaturated fatty acids intake and breast cancer risk: The Japan Public Health Center‐based prospective study

Limited and inconsistent studies exist on the association between the intake of fish, n ? 3 polyunsaturated fatty acids (PUFA) and n ? 6 PUFA and breast cancer. Fish and n ? 3 PUFA support various body functions and are thought to reduce the carcinogenesis risk while n ? 6 PUFA may have a positive association with cancer risk. We examined the association between intake of fish, n ? 3 PUFA [including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha‐linolenic acid (ALA)] and n ? 6 PUFA and breast cancer with subanalyses on estrogen (ER) and progesterone receptor (PR) status. We investigated 38,234 Japanese women aged 45–74 years from the Japan Public Health Center‐based prospective study (JPHC study), and during 14.1 years of follow‐up time, 556 breast cancer cases were newly diagnosed. Breast cancer risk was not associated with the intake of total fish, n ? 3 PUFA and n ? 6 PUFA when analyzed in totality through multivariable Cox proportional hazards regression models with age as the time scale. Intake of total n ? 6 was positively associated with the development of ER+PR+ tumors [multivariable‐adjusted HR _Q4 vs. _Q1 = 2.94 (95% CI: 1.26–6.89; p_trend = 0.02)]. Intake of EPA was associated with a decreased breast cancer risk for ER+PR+ tumors [multivariable‐adjusted HR _Q2 vs. _Q1 = 0.47 (95% CI: 0.25–0.89; p_trend =0.47)]. While the overall association between the intake of total fish, n ? 3 PUFA and n ? 6 PUFA and breast cancer risk is null, for ER+PR+ tumors, a positive association was seen between n ? 6 intake and breast cancer, and a marginally significant inverse association was observed for EPA intake.     

Association between plasma 25-hydroxyvitamin D and colorectal adenoma according to dietary calcium intake and vitamin D receptor polymorphism

The anticarcinogenic potential of vitamin D might be mediated by not only calcium metabolism but also other mechanisms initiated by vitamin D receptor (VDR). The authors measured plasma 25-hydroxyvitamin D in healthy volunteer examinees who underwent total colonoscopy in Tokyo, Japan, 2004-2005, and evaluated its influence on colorectal adenoma, both alone and in interaction with VDR polymorphisms, which correspond to the FokI and TaqI restriction sites. The main analysis of plasma 25-hydroxyvitamin D included 737 cases and 703 controls. Compared with the lowest quintile of plasma 25-hydroxyvitamin D, only the highest was related to a significantly decreased odds ratio of colorectal adenoma (odds ratio = 0.64, 95% confidence interval: 0.45, 0.92). In contrast, all but the lowest quintile of dietary calcium intake presented similarly reduced odds ratios (odds ratio for the highest = 0.67, 95% confidence interval: 0.47, 0.95). Of note, the association between plasma 25-hydroxyvitamin D levels and colorectal adenoma was modified by the TaqI polymorphism of the VDR gene (P(interaction) = 0.03) but not by dietary calcium intake (P(interaction) = 0.93). These observations highlight the importance of vitamin D in colorectal tumorigenesis. Vitamin D might protect against colorectal neoplasia, mainly through mechanisms other than the indirect mechanism via calcium metabolism.