Mei-Hsuan Wu

Anthropometric measures, plasma adiponectin, and breast cancer risk

Adiponectin is a peptide hormone secreted exclusively by adipocytes, and obesity is an established risk factor for breast cancer. We have, thus, evaluated the associations of anthropometric measures of adiposity and adiponectin with the development of breast cancer in a case-control study. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 244 incident cases with breast cancer, including 141 premenopausal and 103 postmenopausal cases, and 244 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2005. Plasma levels of adiponectin were measured by RIA. The relationship between anthropometric measures of adiposity and breast cancer risk was modified by menopausal status, with a significant increase in risk observed in postmenopausal but not premenopausal women. Moreover, a fairly robust inverse association of adiponectin with the risk was observed only in postmenopausal women (adjusted odds ratio (OR), 0.55; 95% confidence interval (CI), 0.23-0.97), but not in premenopausal women. Additionally, the plasma adiponectin levels tended to be inversely associated with estrogen receptor (ER)-positive (adjusted OR, 0.53; 95% CI, 0.27-0.98) but not ER-negative breast tumors. Furthermore, the associations of adiponectin with breast cancer risk overall and by menopausal and ER status remained after adjustment for obesity indices. These results suggest that adiponectin may have an independent role in breast carcinogenesis, particularly in the postmenopausal and ER-positive breast cancer risk.

Genetic variants of myeloperoxidase and catechol-O-methyltransferase and breast cancer risk.

This nested case–control study evaluated the role of polymorphisms in the myeloperoxidase (MPO) and catechol-O-methyltransferase (COMT) genes that modulate oxidative stress in breast cancer risk in a Chinese population. Our results demonstrate that the MPO A/A genotype was associated with a reduced risk of breast cancer (odds ratio (OR) 0.64; 95% confidence interval (CI) 0.11–3.76), whereas there was no overall association of COMT genotype with breast cancer. Of note, an elevated breast cancer risk associated with the increasing numbers of high-risk genotypes of MPO and COMT genes was observed in women with a longer duration between menarche and first full-term pregnancy.

Vitamin D Decreases Risk of Breast Cancer in Premenopausal Women of Normal Weight in Subtropical Taiwan

Background Evidence for an association between vitamin D status and breast cancer is now more convincing, but is uncertain in subtropical areas like Taiwan. This hospital-based case-control study examined the relationship of breast cancer with vitamin D intake and sunlight exposure. Methods A total of 200 incident breast cancer cases in a Taipei hospital were matched with 200 controls by date of interview and menopausal status. Information on risk factors for breast cancer was collected in face-to-face interviews and assessed with reference to vitamin D intake (foods and nutrients) and sunlight exposure. Vitamin D intake was divided into quartiles, and threshold effect was evaluated by comparing Q2–Q4 with Q1. Results After controlling for age, education, parity, hormone replacement therapy, body mass index (BMI), energy intake, menopausal status, and daily sunlight exposure, the risk of breast cancer in participants with a dietary vitamin D intake greater than 5 µg per day was significantly lower (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.24–0.97) than that of participants with an intake less than 2 µg per day. In analysis stratified by menopausal status and BMI, both dietary vitamin D and total vitamin D intakes were associated with a protective effect among premenopausal women. There was a significant linear trend for breast cancer risk and dietary vitamin D intake in premenopausal women (P = 0.02). In participants with a BMI lower than 24 kg/m2 (ie, normal weight), dietary vitamin D intake was inversely related to breast cancer risk (P for trend = 0.002), and a threshold effect was apparent (Q2–Q4 vs Q1: OR, 0.46; 95% CI, 0.23–0.90). Conclusions Vitamin D had a protective effect against breast cancer in premenopausal women of normal weight in subtropical Taiwan, especially an intake greater than 5 µg per day.

Relationships between critical period of estrogen exposure and circulating levels of insulin-like growth factor-I (IGF-I) in breast cancer: evidence from a case-control study.

Epidemiological observations suggest that insulin‐like growth factor‐I (IGF‐I), a potent mitogenic and anti‐apoptotic peptide, plays a role in the etiology of breast cancer. Estrogen, which is crucial in breast carcinogenesis, both regulates and is influenced by IGF‐I family. A case‐control study was conducted to assess the role of IGF‐I as a biomarker for breast cancer and to evaluate the potential joint effect of circulating IGF‐I and critical period of estrogen exposure, as estimated by the interval between age at menarche and age at first full‐term pregnancy on the risk of breast cancer. Questionnaire information 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 2006. Plasma levels of IGF‐I and IGFBP‐3 were measured by immunoradiometric assay. Conditional logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Our case‐control data indicate that breast cancer risk related to IGF‐I differs according to menopausal status. High circulating levels of IGF‐I increased risk of pre‐ but not postmenopausal breast cancer (top vs. bottom tertile, adjusted OR, 1.86; 95% CI, 1.01–3.44). Furthermore, elevated IGF‐I concentrations in conjunction with prolonged interval of critical period of estrogen exposure were associated with significantly increased risk of breast cancer, particularly among estrogen‐positive cases (adjusted OR, 2.42, 95% CI, 1.33–4.38). These results suggest that the joint effect of IGF‐I and estrogens may provide novel methods of breast cancer risk reduction among women.

Androgen receptor gene CAG repeats, estrogen exposure status, and breast cancer susceptibility

The length of a polymorphic CAG repeat in exon 1 of the androgen receptor (AR) is inversely correlated with AR transactivation activity. As heightened androgenic stimulation may oppose breast cell proliferation, which is mediated by AR, we examined whether AR-CAG repeat lengths are related to breast cancer susceptibility. A nested case–control study of 88 newly diagnosed cases of breast cancer between 1992 and 2000 and 334 matched controls was carried out in Taiwanese women. Risk factors were obtained through a standardized questionnaire interview and blood samples were collected and used to determine the number of AR-CAG repeats. Women with one or more long AR (CAG)n repeat alleles (>22 repeats) were not at significantly increased risk of breast cancer [odds ratio (OR), 1.52; 95% confidence interval (CI), 0.80–2.90]. Of particular interest was a significantly increased risk associated with the long-allele AR genotype that was present mostly among women with a short duration (<10 years) of early estrogen exposure, as indicated by the interval between age at menarche and age at first full-term pregnancy, as compared with short AR allele genotypes (OR, 2.70; 95% CI, 1.00–7.31), although no such significant association in women with a long duration of early estrogen exposure (OR, 0.70; 95% CI, 0.25–1.59) was detected. These data suggest that longer AR (CAG)n repeat alleles may confer an increased risk of breast cancer among particular subsets of individuals, although these findings need replication in other populations.