The present case -control study was to investigate the relationships of plasma leptin level and anthropometric measures of adiposity with the risk of breast cancer. Questionnaire information, anthropometric measures and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei, between 2004 and. Plasma levels of leptin were measured by RIA. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for assessing the associations. Overall, higher leptin concentrations were significantly associated with an increased risk of breast cancer (OR (95% CI) for top vs bottom tertile of leptin was 1.63 (1.07 -2.49), P trend ¼ 0.009). Waist circumference was a significant anthropometric factor for breast cancer in both pre-and postmenopausal women. Furthermore, the associations of leptin with breast cancer risk remained after adjustment for obesity indices. These results suggest that leptin may have an independent role in breast tumorigenesis. Regardless of the impact of circulating leptin, more research is needed to elucidate molecular mechanisms and local leptin levels that are critical for the development of breast cancers. British Journal of Cancer (2009) Epidemiologic evidence suggested that obesity is associated with an increased risk of breast cancer in women, primarily in postmenopausal population (Calle and Thun, 2004). However, the molecular mechanisms underlying the obesity -breast cancer link are not fully clear. One important factor contributing to obesity -breast carcinogenesis might be an excess exposure of mammary epithelium to various bioactive substances produced by the adipose tissue (adipokines). Indeed, adipose tissue is a source of oestrogens, insulin and insulin-like growth factors, all of which are believed to be involved in mammary tumorigenesis (Schäffler et al, 2007). The most prominent adipokine is leptin, which is best known as a regulator of food intake and energy balance in the hypothalamus (Auwerx and Staels, 1998). Interestingly, leptin is also implicated in the regulation of reproductive hormones and function . Notably, leptin consistently stimulates the proliferation of benign and malignant epithelial breast cells in vitro as measured by DNA synthesis and upregulation of downstream regulators of cellular proliferation (Dieudonne et al, 2002;Hu et al, 2002). Thus, the intriguing possibility exists that leptin could be directly related to breast carcinogenesis by underlying the effects of obesity on cancer development. We have undertaken a case -control study to test this hypothesis. MATERIALS AND METHODS Case and control selectionThis case -control study was conducted at the Tri-Service General Hospital, Taipei, Taiwan, from January 2004 to November 2006. To account for the notions that type 2 diabetes and metabolic syndrome (MS) have been associated with increased serum leptin levels and elevated risk of breast cancer (Vona-D...

Adipocytokine resistin is a member of the newly discovered family of cysteine-rich protein. Recent data suggest that macrophages are a major source of human resistin. Given the obesity-breast cancer link and convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and breast cancer risk in humans. We conducted a hospital-based case-control study to evaluate whether plasma resistin levels were associated with breast cancer risk in women. We also examined the modification effect of estrogen exposures on the resistin-breast cancer link. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 380 incident cases with breast cancer and 760 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2008. Plasma levels of resistin were measured by enzyme immunoassay. Cumulative exposure to estrogens were estimated according to the age at menarche and age at enrollment for premenopausal women and age at menarche and age at menopause for postmenopausal women. Cases with breast cancer had significantly elevated resistin concentrations as compared with control subjects. Compared with those in the lowest quartile, the adjusted odds ratios of breast cancer for women in the second, third, and highest quartiles were 1.48 [95% confidence interval (CI) = 0.65-3.38], 1.76 (95% CI = 1.00-4.73), and 2.08 (95% CI = 1.04-3.85), respectively. Furthermore, the biological gradient of breast cancer risk by plasma resistin levels remained after adjustment for measures of adiposity. The dose-dependent relationship of resistin levels with breast cancer risk was notably pronounced among women with excess exposure to estrogens. Adipocytokine resistin may have an adiposity-independent role in breast carcinogenesis. Mechanistic studies to fully elucidate the mechanisms underlying resistin's effects should be pursued in future investigations.

BackgroundB vitamins, including vitamin B6, are coenzymes that are important for DNA integrity and stability. Deficiencies in B vitamins may promote tumor carcinogenesis.MethodsWe examined the association of dietary vitamin B6 intake with overall breast cancer risk and breast cancers stratified by hormone receptor status. This case-control study included 391 breast cancer cases and 782 control subjects enrolled at the Tri-Service General Hospital in Taipei, Taiwan. Energy-adjusted intake of vitamin B6 was derived from a food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.ResultsAs compared with women in the lowest tertile, the multivariate-adjusted ORs for breast cancer among women in the second and highest tertiles of vitamin B6 intake were 0.78 (95% CI, 0.64–2.52) and 0.64 (0.26–0.92), respectively. In addition, higher vitamin B6 intake was associated with a significantly lower risk of developing ER-negative breast tumors.ConclusionsOur findings suggest that higher intake of vitamin B6 is associated with a reduction in breast cancer risk, particularly ER-negative tumors.

Peroxisome proliferator-activated receptor γ (PPARγ) has been linked with possible antineoplastic effects in colorectal carcinogenesis. However, data for the possible link between PPARγ and breast cancer risk are sparse. We assessed the association of three polymorphisms in PPARγ (rs10865710 [C-681T], rs1805192 [Pro12Ala], and rs3856806 [C1431T]) with the risk of breast cancer in an ethnic Chinese female population in Taiwan. In addition, interactions with estrogen exposures were also explored. Genotypes for the PPARγ polymorphisms were determined on 291 incident breast cancer cases and 589 matched controls by fluorogenic 5'-nuclease assay. The at-risk haplotypes were defined according to the three polymorphisms in the following order: C-681T, Pro12Ala, and C1431T, which include CCT, GGT, and GGC. In addition, a critical period of estrogen exposure was estimated by the interval between age at menarche and age at first full-term pregnancy. Overall, there was no evidence of a significant impact of individual polymorphisms of PPARγ on breast cancer risk. However, the haplotype analysis revealed that women harboring at-risk haplotypes showed a significant 67% increase in breast cancer risk [adjusted odds ratio (OR) 1.67; 95% confidence interval (CI) 1.11-2.52]. Furthermore, there was a significant joint effect of estrogen exposure-related factors and at-risk haplotypes of PPARγ on breast cancer risk (adjusted OR 4.04; 95% CI 1.89-8.65), particularly in premenopausal women. The present study implicates a role for PPARγ in breast cancer risk. Mechanistic studies to fully elucidate the mechanisms underlying PPARγ's effects should be pursued in future investigations.

The role of atopic dermatitis (AD) in the development of colorectal cancer (CRC) has been a matter of scientific debate with mixed results. We conducted a nationwide cohort study to assess the association between AD and risk of CRC. Drawing on Taiwan's National Health Insurance Research Database, 46,703 patients with AD (the AD cohort) and 186,812 sex, age, and index year-matched patients without AD (the non-AD cohort) were identified in the period between 2000 and 2008. Follow-up time was calculated from the date of entry in the cohort until the occurrence of a first CRC diagnosis, death, or the end of the observation period (December 31, 2013), whichever occurred first. Hazards ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Fine-Gray competing risk model were used to estimate the association between AD and CRC risk. After multivariable adjustment, AD was associated with an increased risk of CRC (adjusted HR, 1.26; 95% CI, 1.14–1.40). Of note, a significant positive association between AD and CRC risk was evident in both men and women and in all age groups. In summary, this population-based cohort study revealed that AD was associated with an increased risk of CRC in an Asian population. It will be of interest for cohort studies with prediagnostic specimens to evaluate the potential relationship between AD and CRC using biomarkers for allergy status.