Associations of erythrocyte ω‐3 fatty acids with biomarkers of ω‐3 fatty acids and inflammation in breast tissue

There is increasing evidence that chronic inflammation is associated with increased breast cancer risk. Long‐chain omega‐3 polyunsaturated fatty acids (LCω‐3PUFA) may reduce circulating biomarkers of inflammation; however associations of blood LCω‐3PUFA with breast tissue LCω‐3PUFA and breast tissue biomarkers of inflammation are not well understood. We conducted a cross‐sectional analysis of breast tissue and blood samples from n = 85 women with no history of breast cancer, who underwent breast reduction surgery. Fatty acids of erythrocytes and undissected breast tissues were analyzed by gas chromatography; C‐reactive protein (CRP), interleukin (IL)–6 and IL‐8 in plasma and tissue were measured by ELISA. Multivariable‐adjusted regression models were used to estimate associations between erythrocyte LCω‐3PUFA and breast tissue biomarkers. Women in the highest erythrocyte LCω‐3PUFA tertile had LCω‐3PUFA concentrations in the breast 73% (95% CI: 31–128%; p trend < 0.0001) higher than women in the lowest tertile. Associations for each individual LCω‐3PUFA were similar in magnitude. No significant association was found for the shorter ω‐3 PUFA, α‐linolenic acid. Although compatible with no association, women in the highest tertile of erythrocyte eicosapentaenoic acid had a nonsignificant 32% (95% CI: ?23 to 62%) reduced breast tissue CRP. No correlation was observed between erythrocyte ω‐3 PUFA and tissue IL‐6 or IL‐8 concentrations. Our findings provide evidence that erythrocyte ω‐3 fatty acids are valid measures of breast tissue concentrations, and limited evidence that inverse associations from prospective epidemiologic studies of blood LCω‐3PUFA and breast cancer risk may be partly explained by reductions in breast tissue inflammation; however, these findings require replication.     

Stem cells from adipose tissue and breast cancer: hype,risks and hope

Several recent papers have generated new hope about the use of white adipose tissue (WAT)-derived progenitor cells for soft tissue reconstruction in a variety of diseases including breast cancer (BC), a procedure that is increasingly used worldwide. We revised the available literature about WAT cells and BC. In the BC field, we believe that the hype for the exciting results in terms of WAT progenitor cell engraftment and tissue augmentation should be tempered when considering the recent and abundant preclinical studies, indicating that WAT progenitors may promote BC growth and metastasis. White adipose tissue progenitors can contribute to tumour vessels, pericytes and adipocytes, and were found to stimulate local and metastatic BC progression in several murine models. Moreover, there are clinical retrospective data showing a significant increase in the local recurrence frequency in patients with intraepithelial neoplasia who received a lipofilling procedure for breast reconstruction compared with controls. Retrospective and prospective clinical trials are warranted to investigate in depth the safety of this procedure in BC. Preclinical models should be used to find mechanisms able to inhibit the tumour-promoting activity of WAT progenitors while sparing their tissue reconstruction potential.     

Opposing associations of serum n-3 and n-6 polyunsaturated fatty acids with colorectal adenoma risk: an endoscopy-based case-control study

Several human and animal studies have shown that n-3 polyunsaturated fatty acids (PUFA) might be associated with a decreased risk, whereas other studies showed that n-6 PUFA may be associated with an increased risk of colorectal cancer. However, results from these studies are not consistent. We evaluated the associations between serum n-3 and n-6 PUFA levels and colorectal adenoma risk in an endoscopy-based case-control study, conducted in The Netherlands between 1997 and 2002. We included 363 cases of colorectal adenomas and 498 adenoma-free controls. Serum fatty acids were measured in cholesteryl esters. Logistic regression models were used to calculate odds ratios (OR), which were adjusted for age, gender and alcohol intake. Total serum n-3 PUFA levels were inversely associated with colorectal adenoma risk, the OR comparing the third tertile with the first tertile was 0.67 [95% confidence interval (CI) 0.46-0.96, p for trend = 0.03]. Serum eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) and the n-3/n-6 ratio were inversely associated with colorectal adenoma risk, but these were not statistically significant. In contrast, the risk of colorectal adenomas was increased by total n-6 PUFA with an OR of 1.68 (95% CI, 1.17-2.42, p for trend = 0.006) and by linoleic acid (LA; C18:2n-6) with an OR of 1.65 (95% CI, 1.15-2.38, p for trend = 0.007). This is the first observational study that simultaneously finds an inverse association of serum n-3 PUFA and a positive association of n-6 PUFA with colorectal adenoma risk.     

Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway

The effect of fish oils and their active omega-3 fatty acid constituents, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were investigated on breast cancer growth. In in vivo experiments, mice were fed diets that were rich in either omega-3 (fish oil) or omega-6 (corn oil) fatty acids. Three weeks after implantation of MDA-MB-231 breast cancer cells, the tumor volume and weight were significantly lower (p < 0.05) for mice fed the omega-3 diets compared to those fed the omega-6 diets. Dietary fish oil also caused a 40% (p < 0.05) increase in neutral sphingomyelinase (N-SMYase) activity in the tumors. The tumor tissues from fish oil-fed animals expressed elevated p21 (waf1/cip1) mRNA, whereas tumor tissues from corn oil-fed animals exhibited undetectable levels of p21 expression. In in vitro experiments, at concentrations as low as 25 muM, DHA and EPA inhibited the growth of cultured MDA-MB-231 cells in a dose-dependent manner by 20-25% (p < 0.05). N-SMYase activity was also increased by 30-40% (p < 0.05) in the DHA- or EPA-treated cells in which an increase in ceramide formation was observed. DHA and EPA were both observed to enhance membrane bleb formation and also to induce the expression of p21. Omega-3 fatty acids-induced bleb formation and p21 expression were inhibited by the N-SMYase inhibitor GW4869, which also inhibited apoptosis by approximately 40% (p < 0.05). The results suggest that inhibition of breast cancer growth in nude mice by dietary fish oil and inhibition of breast cancer cell growth in culture by treatment with DHA and EPA is mediated by activation of N-SMYase.     

Longchain serum fatty acids and risk of thyroid cancer: A population-based case-control study in Norway

Epidemiologic studies have shown an association between seafood consumption and risk of thyroid cancer. Fish meals increase the serum concentrations of the longchain fatty acids, eicosapentaenoic acid (205,n-3) (EPA) and docosahexaenoic acid (226,n-3) (DHA), for days. The hypothesis that serum concentrations of fatty acids may be associated with thyroid cancer risk therefore was tested in a population-based case-control study with 74 cases and 221 matched controls. Seventy-three cases with sera in the Norwegian serum bank (JANUS) were identified in the Norwegian Cancer Registry and matched with three controls, also in JANUS, on age, gender, place of residence, and time of blood sampling. Each case was matched with two controls. Serum concentrations of 11 longchain fatty acids were determined blindly by gas chromatography for all subjects. Controls were divided into three groups with increasing serum fatty acid concentrations, and odds ratios between cases and controls were estimated relative to the group with lowest serum level by univariate and multivariate analyses. The main finding was a significant inverse relation between the sum of arachidonic acid (204,n-6) (AA) and DHA serum concentrations and thyroid cancer risk. The significance of this association was weakened when the analyses were restricted to the papillary type of thyroid carcinoma. It was of the same order of magnitude whether the period between blood sampling and diagnosis was greater than eight years, or eight or less years. High EPA/AA ratio, indicating consumption of fish fat, was not associated significantly with increased thyroid-cancer risk. These data indicate that the association between seafood ingestion and increased thyroid-cancer risk may not be caused by the marine fatty acids.     

Essential fatty acid consumption and risk of breast cancer

Summary Animal and ecological studies of essential fatty acids suggest that omega-3 fatty acids found in fish oils and omega-6 fatty acids found in vegetable oils may be playing a role in the etiology of breast cancer. Essential fatty acids may modulate breast cancer risk by interacting with prostaglandins, which have immunosuppressive and platelet aggregative capabilities. The fatty acid composition of adipose tissue reflects the dietary consumption of essential fatty acids over a period of years. Biochemical techniques have been used in epidemiological studies to accurately estimate fatty acid consumption. However, analytical epidemiology studies that have used biochemical measurements of adipose tissue fatty acid composition, have not supported a relationship between consumption of these essential fatty acids and breast cancer risk.     

Breast cancer risk and erythrocyte compositions of n-3 highly unsaturated fatty acids in Japanese

Dietary intake of fish rich in n-3 highly unsaturated fatty acids (HUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been proposed to decrease cancer risk. In contrast to results from laboratory studies, however, protective effects for breast cancer have proved equivocal in epidemiological studies. In the present case-control study, we examined associations between breast cancer risk and fatty acid compositions in erythrocyte membranes as biomarkers for those intakes. Dietary information and blood samples were collected from 103 incident breast cancer cases and 309 non-cancer controls (matched by age and season) and erythrocyte fatty acids were measured using accelerated solvent extraction and gas-liquid chromatography. Dietary intake of n-3 HUFAs demonstrated a negative association with risk (the highest to the lowest tertile, odds ratio (OR), 0.51; 95% confidence interval (CI), 0.27-0.98; p(trend)<0.05), but there was no association with those of saturated fatty acids (SFAs) and meat. Moreover, risk was inversely associated with erythrocyte compositions of EPA (OR, 0.27; 95% CI, 0.14-0.53; p(trend)<0.0001), DHA (OR, 0.06; 95% CI, 0.02-0.16; p(trend)<0.0001) and n-3 HUFAs (OR, 0.11; 95% CI, 0.05-0.24; p(trend)<0.0001), and positively with that of SFAs (OR, 12.29; 95% CI, 4.94-30.57; p(trend)<0.0001) and the ratio of SFAs/n-3 HUFAs (OR, 14.65; 95% CI, 5.67-37.82; p(trend)<0.0001). In conclusion, we showed that erythrocyte compositions of specific fatty acids derived from fish intake, as biomarkers, are associated with lower risk of breast cancer, but further studies are needed to investigate mechanisms linked to the etiology.     

Erythrocyte membrane fatty acids and breast cancer risk: a prospective analysis in the nurses' health study II

The roles of specific fatty acids in breast cancer etiology are unclear, particularly among premenopausal women. We examined 34 individual fatty acids, measured in blood erythrocytes collected between 1996 and 1999, and breast cancer risk in a nested case‐control study of primarily premenopausal women in the Nurses' Health Study II. Breast cancer cases diagnosed after blood collection and before June 2010 (n = 794) were matched to controls and conditional logistic regression was used to estimate OR's (95% CI's) for associations of fatty acids with breast cancer; unconditional logistic regression was used for stratified analyses. Fatty acids were not significantly associated with breast cancer risk overall; however, heterogeneity by body mass index (BMI) was observed. Among overweight/obese women (BMI ≥ 25), several odd‐chain saturated (SFA, e.g. 17:0, OR_Q4vsQ1(95% CI) =1.85 (1.18 – 2.88), p_trend=0.006 p_int<0.001), trans (TFA, e.g. 18:1, OR_Q4vsQ1(95% CI) =2.33 (1.45 – 3.77), p_trend<0.001, p_int=0.007) and dairy‐derived fatty acids (SFA 15:0 + 17:0 + TFA 16:1n‐7t; OR_Q4vsQ1(95% CI) =1.83(1.16 – 2.89), p_trend=0.005, p_int<0.001) were positively associated, and n‐3 polyunsaturated fatty acids (n‐3 PUFA, e.g. alpha‐linolenic acid; OR_Q4vsQ1(95% CI) =0.57 (0.36 – 0.89), p_trend=0.017, p_int=0.03) were inversely associated with breast cancer. Total SFA were inversely associated with breast cancer among women with BMI < 25 (OR_Q4vsQ1(95% CI) =0.68 (0.46 – 0.98), p_trend=0.05, p_int=0.01). Thus, while specific fatty acids were not associated with breast cancer overall, our findings suggest positive associations of several SFA, TFA and dairy‐derived fatty acids and inverse associations of n‐3 PUFA with breast cancer among overweight/obese women. Given these fatty acids are influenced by diet, and therefore are potentially modifiable, further investigation of these associations among overweight/obese women is warranted.     

Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case-control study

Experimental studies suggest that the risk of prostate cancer is reduced with the intake of long-chain n-3 polyunsaturated fatty acids derived from marine foods, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, few human studies have been conducted due to difficulties in assessing the dietary intake of these fatty acids. The authors examined the relationship between prostate cancer risk and EPA and DHA in erythrocyte biomarkers in a population-based case-control study in Auckland, New Zealand during 1996-1997 involving 317 prostate cancer cases and 480 age-matched community controls. Reduced prostate cancer risk was associated with high erythrocyte phosphatidylcholine levels of EPA (multivariate relative risk = 0.59; 95% confidence interval 0.37-0.95, upper vs lowest quartile) and DHA (multivariate relative risk = 0.62; 95% confidence interval 0.39-0.98, upper vs lowest quartile). These analyses support evidence from in vitro experiments for a reduced risk of prostate cancer associated with dietary fish oils, possibly acting via inhibition of arachidonic acid-derived eicosanoid biosynthesis.     

Intake of n-3 and n-6 polyunsaturated fatty acids and development of colorectal cancer by subsite: Japan Public Health Center-based prospective study

To date, epidemiologic studies investigating intake of n-3 and n-6 polyunsaturated fatty acids and risk of colorectal cancer are limited, and results remain inconsistent. This is the first prospective study to show the association by subsite (proximal colon, distal colon, rectum). To clarify the role of n-3 and n-6 polyunsaturated fatty acids intake in colon carcinogenesis, we conducted a large, population-based prospective study, characterized by high fish consumption and a wide range of n-3 polyunsaturated fatty acids intakes. Subjects were followed from response to a lifestyle questionnaire in 1995-1999 through 2006. During 827,833 person-years of follow-up (average 9.3 years), we identified 1,268 new colorectal cancer cases (521 colon and 253 rectal for men; 350 colon and 144 rectal for women). Compared to the lowest quintile, the relative risk and 95% confidence interval of developing cancer among the fifth quintile of marine n-3 polyunsaturated fatty acids intake were 0.60 and 0.31-1.14, respectively (p for trend = 0.04) in the colon in women and 0.35 and 0.14-0.88 (p for trend = 0.05) and 1.82 and 0.79-4.20 (p for trend = 0.16) in the proximal and distal colon, respectively, in men. For rectal cancer, the dose response for marine n-3 polyunsaturated fatty acids s was unclear; rather, we observed U-shaped associations in men and women. We found no evidence that n-6 polyunsaturated fatty acids increases or the n-3/n-6 ratio decreases the risk of colorectal cancer. Our results suggest that intake of marine n-3 polyunsaturated fatty acids may be inversely related to the risk of cancer in the proximal site of the large bowel.     

Serum enterolactone concentration is not associated with breast cancer risk in a nested case-control study

The lignan enterolactone produced by the intestinal microflora from dietary precursors has been hypothesized to protect against hormone-dependent cancers. We conducted a nested case-control study to examine the relationship between serum enterolactone concentration and risk of breast cancer. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum collected at 4 independent cross-sectional population surveys from 206 women with breast cancer diagnosed during follow-up (mean 8.0 years) and from 215 controls frequency-matched to cases by study cohort, 5-year age group and study area. Mean serum enterolactone concentration (nmol/l) did not significantly differ between case and control subjects [25.2 (SD 22.2) vs. 24.0 (SD 21.3), respectively]. Odds ratios for breast cancer risk estimated by conditional logistic regression for increasing concentration of enterolactone in quartiles were 1.00 (referent), 1.67 (95% CI 0.95-2.95), 1.71 (95% CI 0.96-3.06) and 1.30 (95% CI 0.73-2.31), and p for trend was 0.48. Our findings do not support the hypothesis that high serum enterolactone concentration is associated with reduced risk of breast cancer.     

n-3 polyunsaturated fatty acid intake and cancer risk in Italy and Switzerland

Data from a series of case-control studies, conducted in Italy and Switzerland between 1991 and 2001, have been analyzed to evaluate the role of n-3 polyunsaturated fatty acid (PUFA) intake in the etiology of cancer of oral cavity and pharynx (736 cases, 1772 controls), esophagus (395 cases, 1066 controls), large bowel (1394 colon, 886 rectum, 4765 controls), breast (2900 cases, 3122 controls) and ovary (1031 cases, 2411 controls). Controls were patients admitted to hospital for acute, non-neoplastic conditions, unrelated to modifications in diet. The multivariate odds ratios (OR) for the highest quintile of n-3 PUFAs compared to the lowest one were 0.5 for oral and pharyngeal cancer, 0.5 for oesophageal cancer, 0.7 for colon cancer, 0.8 for rectal and breast cancer and 0.6 for ovarian cancer; the estimates and the trends in risk were significant for all cancer sites, excluding rectal and breast cancer. The estimates for an increase in n-3 PUFAs of 1 g/week were 0.70 for oral and pharyngeal cancer, 0.71 for oesophageal, 0.88 for colon, 0.91 for rectal, 0.90 for breast and 0.85 for ovarian cancer. All the estimates were statistically significant, excluding that for rectal cancer, and consistent across strata of age and gender. These results suggest that n-3 PUFAs decrease the risk of several cancers.     

Dietary and other risk factors in women having fibrocystic breast conditions with and without concurrent breast cancer: a nested case-control study in Shanghai, China

Risk of breast cancer is increased in women with proliferative benign breast conditions. Most of these conditions, however, do not progress to breast cancer. The purpose of our study was to identify factors possibly associated with this progression. Women with proliferative fibrocystic breast conditions alone (214), and women with proliferative fibrocystic breast conditions and concurrent breast cancer (130), were compared to each other, and each of these groups of women were also compared to 1,070 controls; and 176 women with non-proliferative benign breast conditions alone, and 155 also with breast cancer, were similarly compared. All study subjects were selected from a cohort of women enrolled in a trial of breast self-examination in Shanghai. Women were interviewed to ascertain information on suspected risk factors for breast cancer and dietary habits. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Increased risks of both proliferative fibrocystic breast conditions alone, and with breast cancer, were associated with low parity, a prior benign breast lump and breast cancer in a first-degree relative. Decreasing trends in the risk of both conditions with increasing intake of fruits and vegetables were observed. No factors were significantly associated with risk of breast cancer relative to risk of proliferative changes. Similar, but in some instances weaker, associations were observed for non-proliferative fibrocystic conditions with and without breast cancer. The possible risk or protective factors that were observed in our study most likely alter the risk of breast cancer at an early stage in the carcinogenic process, and probably do not alter risk of progression from proliferative fibrocystic breast conditions to breast cancer.     

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.     

Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study

Laboratory and epidemiological data have linked vitamin D to breast cancer prevention. Beside dietary intake, endogenous production of vitamin D substantially contributes to a subject's vitamin D status. Most studies, however, have assessed dietary intake only. Although differential effects of vitamin D on premenopausal and postmenopausal breast cancer have been discussed, this is the first study to investigate the association of plasma 25-hydroxyvitamin D [25(OH)D], as indicator of the overall vitamin D status, with breast cancer risk with restriction to premenopausal women only. We used data of a population-based case-control study comprising 289 cases and 595 matched controls. Information on sociodemographic and breast cancer risk factors was collected by questionnaire and plasma 25(OH)D was measured by enzyme immunoassay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. We observed a significant inverse association between breast cancer risk and plasma 25(OH)D concentrations. Compared with the lowest category (<30 nmol/L), the ORs (95% CI) for the upper categories (30-45, 45-60, >or=60 nmol/L) were 0.68 (0.43-1.07), 0.59 (0.37-0.94) and 0.45 (0.29-0.70), respectively (p(trend) = 0.0006). The association was shown to be nonlinear (p(nonlinearity) = 0.06) in fractional polynomial analysis with a stronger effect in women at low plasma 25(OH)D levels, providing some evidence of a threshold effect (at circa 50 nmol/L). The association was stronger in progesterone receptor negative tumors, with suggestive evidence of effect heterogeneity (p(heterogeneity) = 0.05, case-only model). Our findings support a protective effect of vitamin D for premenopausal breast cancer.     

Lifelong vegetarianism and risk of breast cancer: a population-based case-control study among South Asian migrant women living in England

To investigate the role of lifelong vegetarianism on the aetiology of female breast cancer, we conducted a population-based case-control study among South Asian migrant women from the Indian subcontinent resident in England. A total of 240 South Asian breast cancer cases were identified from 2 cancer registries during 1995-1999. For each case, 2 age-matched South Asian controls were randomly selected from the age-sex register of the case practice. Lifelong vegetarians had a slight reduction, although not statistically significant, in the odds of breast cancer relative to lifelong meat-eaters, which persisted after adjustment for socio-demographic and reproductive variables [odds ratio (OR)=0.77; 95% confidence interval (CI)=0.50-1.18]. Analysis by food group revealed no linear trend in the odds of breast cancer with increasing consumption of meat (p=0.10) but the odds were higher for women in the top 75%. In contrast, there were strong inverse trends in the odds of breast cancer with increasing intake of vegetables (p=0.005), pulses (p=0.007) and fibre [non-starch polysaccharides, NSP (p=0.02)], with women in the highest 25% of intake of these foods having about 50% of the odds of those in the lowest ones. Adjustment for intake of vegetables and pulses reverted the odds of breast cancer in lifelong vegetarians relative to lifelong meat-eaters (OR=1.04; 95% CI=0.65-1.68) and attenuated the quartile-specific estimates for meat intake, whereas the inverse trends in the odds of breast cancer with intake of vegetables and pulses remained after adjustment for type of diet or meat intake. These findings suggest that lifelong vegetarianism may be associated with a reduction in the risk of breast cancer through its association with a higher intake of vegetables and pulses. Although it is not possible to exclude the possibility that lifelong meat abstention may also play a role, the findings provide evidence that a diet rich in vegetables and pulses, such as those typically found in South Asian diets, may be protective against this cancer.     

Vitamin E concentration in breast adipose tissue of breast cancer patients (Kuopio, Finland)

Previous data on animals and humans suggest that vitamin E may be a protective factor against cancer. A low dietary vitamin E intake has been suggested to increase the risk of breast cancer. We examined the dietary intake and the concentration of vitamin E in breast adipose tissue of women in Kuopio, Finland, diagnosed between 1990 and 1992 with benign breast disease (n=34) and with breast cancer (n=32). In postmenopausal women, lower dietary intake (P=0.006) and a smaller concentration of vitamin E in breast adipose tissue (P=0.024) were observed in breast cancer patients than in subjects with benign breast disease. Partial correlation showed that the vitamin E concentration in the breast adipose tissue correlated positively with the dietary intake of vitamin E (r=0.25, P=0.023), indicating that the vitamin E concentration in breast adipose tissue reflects the dietary intake of vitamin E.Drs Zhu and Uusitupa are with the Department of Clinical Nutrition, University of Kuopio, Finland, Dr Parviainen is with the Laboratory of Helsinki University, Central Hospital, Helsinki, Finland. Drs Männistö and Pietinen are with the Department of Nutrition, National Public Health Institute, Helsinki, Finland Dr Eskelinen is with the Department of Surgery, and Dr Syrjänen is with the Department of Pathology, University of Kuopio. Address correspondence to Professor Uusitupa, Department of Clinical Nutrition, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. This study was supported by research grants from the Finnish Cancer Society, and by EVO funding for the Breast Cancer Project of Kuopio Cancer Research Center from the Kuopio University Hospital, Finland.     

三阴性乳腺癌中SOCS3及IL-6的表达

目的:探讨三阴性乳腺癌组织中细胞因子信号转导抑制因子-3（SOCS3）以及白细胞介素-6（IL-6）表达情况及其临床意义。方法:收集2012年6月至2014年12月行手术切除并且经病例诊断为三阴性乳腺癌的石蜡包埋组织标本67例、癌旁乳腺组织标本23例以及乳腺纤维瘤标本40例,采用免疫组织化学方法检测各标本中SOCS3以及IL-6的表达情况,此外收集67例三阴性乳腺癌患者临床资料,比较SOCS3以及IL-6的表达与其临床病理特征之间的关系。结果:SOCS3以及IL-6在三种组织中的阳性率具有显著性差异（P＜0.05）,SOCS3阳性率在癌旁乳腺组织中最高,而在三阴性乳腺癌组织中最低,IL-6阳性在三阴性乳腺癌率组织中最高,而在癌旁乳腺组织中最低;经Spearman等级相关性分析,SOCS3与IL-6的表达呈显著负相关关系（r=-0.641,P＜0.05）;SOCS3的阳性表达与三阴性乳腺癌患者的淋巴结转移、肿瘤大小、TNM分级、p53以及Ki-67有关（P＜0.05）;IL-6的阳性表达与三阴性乳腺癌患者的淋巴结转移、肿瘤大小、p53以及Ki-67有关（P＜0.05）。结论:在三阴性乳腺癌当中,SOCS3与IL-6表达呈显著负相关关系,并且SOCS3及IL-6与三阴性乳腺癌的发展过程有关,提示SOCS3以及IL-6可作为潜在的靶向治疗因子进行深入研究。