Genetic Polymorphisms of Paraoxonase 1 (PON1) Gene: Association Between L55M or Q192R with Breast Cancer Risk and Clinico-Pathological Parameters

The aim of the present study was to evaluate the association between the paraoxonase 1 (PON1) L55M and Q192R polymorphisms and breast cancer risk as well as clinico-pathological characteristics of the patients. Genotyping of these polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy. The genotype (P = 0.023) and allele (P = 0.008) frequencies of L55M polymorphism were significantly different between the breast cancer cases and normal individuals. However, the distribution of genotype (P = 0.333) and allele (P = 0.163) frequencies of Q192R polymorphism showed lack of statistical significance. Women who were MM homozygotes (OR = 2.229; 95% CI, 1.219–4.075) and carriers of M allele genotype (OR = 1.429; 95% CI, 1.035–1.974) or M allele (OR = 1.397; 95% CI, 1.093–1.785) were associated with increased risk of breast cancer. However, women who were heterozygous (OR = 0.793; 95% CI, 0.567–1.110) or homozygous (OR = 0.746; 95% CI, 0.407–1.370) for R allele or carriers of R allele (OR = 0.838; 95%, 0.654–1.074) were not associated with breast cancer risk. The M allele genotype was significantly associated with estrogen receptor negativity (P = 0.046) and nodal involvement (P = 0.004) but R allele genotype was not associated with any of the clinico-pathological characteristics. In conclusion, our findings suggest that the polymorphic variant of L55M polymorphism could be a useful genetic marker for tumor prognosis and to identify women who might be at greater risk of developing breast cancer in a hospital-based Malaysian population.     

Gene expression profile testing for breast cancer and the use of chemotherapy, serious adverse effects, and costs of care

As gene expression profile (GEP) testing for breast cancer may provide additional prognostic information to guide the use of adjuvant chemotherapy, we examined the association between GEP testing and use of chemotherapy, serious chemotherapy-related adverse effects, and total charges during the 12 months following diagnosis. Medical record review was conducted for women age 30–64 years, with incident, non-metastatic, invasive breast cancer diagnosed 2006–2008 in a large, national health plan. Of 534 patients, 25.8% received GEP testing, 68.2% received chemotherapy, and 10.5% experienced a serious chemotherapy-related adverse effect. GEP testing was most commonly used in women at moderate clinical risk of recurrence (52.0 vs. 25.0% of low-risk women and 5.5% of high-risk). Controlling for the propensity to receive GEP testing, women who had GEP were less likely to receive chemotherapy (propensity adjusted odds ratio, 95% confidence interval 0.62, 0.39–0.99). Use of GEP was associated with more chemotherapy use among women at low risk based on clinical characteristics (OR = 42.19; CI 2.50–711.82), but less use among women with a high risk based on clinical characteristics (OR = 0.12; CI 0.03–0.47). Use of GEP was not associated with chemotherapy for the moderate risk group. There was no significant relationship between GEP use and either serious chemotherapy-associated adverse effects or total charges. While GEP testing was associated with an overall decrease in adjuvant chemotherapy, we did not find differences in serious chemotherapy-associated adverse events or charges during the 12 months following diagnosis.     

State vocational services and employment in cancer survivors

Background  This study investigated the association of state vocational rehabilitation services in the USA and work outcomes of cancer survivors who were unemployed prior to receipt of services. Methods  Administrative data obtained during fiscal year 2005 from the Rehabilitation Services Administration (RSA) database consisting of 1,201 closed cases with the diagnosis of cancer formed the sample of this study. All cancer survivors were unemployed at the time of application. Data on demographic characteristics, employment and vocational service variables were extracted and analyzed in relation to employment outcome data. Multivariate logistic regression was used to examine the relationship among services provided and work outcomes accounting for demographic characteristics of the participants. Results  Cancer survivors represented 0.4% of the total population that received vocational services in the state-federal vocational rehabilitation program. Of the unemployed cancer survivors who received services, 903 (57%) achieved successful employment while 670 (43%) were not employed following receipt of services. Gender (women; OR = 0.77, 95% CI = 0.61–0.97), lower educational levels (OR = 0.52, 95% CI = 0.33–0.81), provision of cash or medical benefits (e.g., Social Security Disability Insurance benefits; OR = 0.64, 95% CI = 0.50–0.82) were all associated with a greater likelihood of being unemployed at the end of vocational services. Counseling (OR = 1.33, 95% CI = 1.02–1.73), miscellaneous training (OR = 1.61, 95% CI = 1.06–2.44), rehabilitation technology services (OR = 1.22, 95% CI = 0.72–2.08), job placement services (OR = 2.37, 95% CI = 1.72–3.27), job search assistance (OR = 1.43; 95% CI = 1.02–2.01) maintenance services (OR = 1.92, 95% CI = 1.29–2.86), and other services (OR = 1.43, 95% CI = 1.07–1.90) were found to be significantly associated with increased odds for employment. Conclusion  Vocational rehabilitation services were found to be associated with employment status. Future studies investigating the specific effects of certain vocational services for unemployed cancer survivors who qualify for these services are warranted. Implications for cancer survivors  Cancer survivors who are seeking employment or experiencing problems maintaining employment who can qualify should be encouraged to pursue services from state vocational rehabilitation agencies. Medical providers should also become familiar with services offered by state vocational rehabilitation agencies and consider the use of these services..     

Health Literacy and Breast Cancer Screening among Mexican American Women in South Texas

Breast cancer is the main cause of cancer deaths for Hispanic women. This study analyzes the role of functional health literacy on mammography screening behavior and adherence of Hispanic women. Survey data from 722 Mexican American women age 40 and over residing in the Lower Rio Grande Valley of Texas in 2008 were used to estimate logistic regression models to assess the role of functional health literacy on mammography screening behavior and adherence. About 51% of survey respondents had a functional health literacy level deemed as inadequate or marginally functional. After adjusting for other factors, women with adequate health literacy levels were more likely to report to have ever had a mammogram (odds ratio [OR] = 2.92; 95% confidence interval [CI] = 1.62–5.28), to have had a mammogram within the last 2 years (OR = 1.70; 95% CI = 1.14–2.53) or to have had one within the last year (OR = 2.30; 95% CI = 1.54–3.43), compared to women with inadequate or marginally adequate functional health literacy levels. Inadequate/marginal functional health literacy is strongly associated with lower mammography screening. Large improvements in breast cancer control in this population may come from either basic advances in health literacy or by tailored approaches to help women with low literacy navigate local health care systems.     

Breast self-examination in long-term breast cancer survivors

Introduction  For many breast cancer survivors, continued surveillance will be necessary to increase the possibility of finding a new diagnosis in an early stage. One such surveillance approach, breast self-examination, has not been studied specifically in breast cancer survivors. The current study was designed to assess the practice of BSE in a sample of long-term breast cancer survivors, and to examine the personal, emotional, cognitive, and health-care provider factors that may contribute to its performance. Methods  Three hundred forty-five breast cancer survivors (34% response rate, 345/1,001) diagnosed with in situ-stage II breast cancer between 1997–2004 at a community hospital provided answers to a mailed, self-report questionnaire. Results  Seventy-six percent of respondents reported that they had performed a BSE in the last 30-days. Forty percent reported performing BSE once/month, 39% more than once/month, and 21% less than once/month since their diagnosis. Most of the women (90%) reported that a doctor or nurse told them to perform a BSE once/month since their diagnosis, although only 69% had actually been shown how to perform a BSE. Consistently, the perception of increased barriers to BSE performance was associated with performance of BSE less than once/month (OR = 1.4, 95% CI 1.2, 1.6; OR = 0.8, 95% CI 0.8, 0.9). In addition, depending on the model, age (OR = 1.1, 95% CI 1.0, 1.2), perceived effectiveness of cancer treatments (OR = 0.7, 95% CI 0.5, 0.9), and perceived benefits of BSE (OR = 0.8, 95% CI 0.7, 0.9) also was associated with differences in BSE performance. Conclusion  The current study suggests that breast cancer survivors between 4 and 11 years from diagnosis practice BSE, although their perception of the barriers to conducting BSE influences the frequency of this behavior. Further examination is needed to understand why some survivors perceive greater barriers to BSE performance than others. Also needed is a prospective examination of BSE performance using behavioral measures in relation to self-report. Implications for cancer survivors  Increased attention should be paid to this particular screening behavior performed by a majority of breast cancer survivors by both researchers and health-care providers alike. Whether survivors perform the behavior correctly and the impact it has on their emotional and cognitive well-being should be further explored. Supported in part by R25T CA87972     

Joint effects of body size,energy intake,and physical activity on breast cancer risk

To evaluate the joint effect of body size, energy intake, and physical activity on breast cancer risk, we analyzed information on body weight history, energy intake, anthropometric measurements, and physical activity patterns in a population based case–control study. Included in this analysis were 3,458 incidence breast cancer cases and 3,474 age-frequency matched controls from the Shanghai Breast Cancer Study. High weight, height, body mass index, waist-to-hip ratio, and weight gain showed stronger associations with breast cancer risk in postmenopausal women than premenopausal women. High total physical activity was inversely associated with postmenopausal breast cancer risk (p for trend = 0.026) and premenopausal breast cancer (p for trend = 0.059). The odds ratios for women with a high waist-to-hip ratio (≥0.84) and low total physical activity (≤10.9 MET-h/day) had the highest risk for breast cancer (OR = 2.7, 95% CI: 1.4–4.9 for postmenopausal women, OR = 2.1, 95% CI: 1.5–3.1 for premenopausal women) compared to their counterpart with low waist-to-hip ratio (<0.76) and high total physical activity (>20.5 MET-h/day). We did not find a statistically significant multiplicative interaction between body size, caloric intake and total physical activity on breast cancer risk.     

Effects of life event stress and social support on the odds of a ≥2 cm breast cancer

Objective  To examine the contribution of life event and social support factors to diagnosis with a ≥2 cm breast cancer. Methods  We studied 1,459 Australian women aged 40–69 diagnosed in 2002–2003 with a first primary invasive breast cancer 1.1 cm or larger. We measured stressful life events, perceived stress levels, and social support in the year before diagnosis and collected information on other potential risk factors and confounders. Results  The odds of a ≥2 cm breast cancer relative to a 1.1–1.9 cm breast cancer were reduced in women who reported tension or change in an intimate relationship in the year before diagnosis (OR = 0.71 95% CI 0.54–0.92; p = 0.009); the reduction was greatest in women living with a partner (OR = 0.64 95% CI 0.47–0.88; p = 0.006) and was largely unaffected by adjustment for other variables independently associated with a ≥2 cm breast cancer in our study. There was no evidence that the total number or severity of all studied life events influenced cancer size. Low partner support increased the odds of a ≥2 cm cancer but only in women not living with a partner. Conclusion  Intimate relationship stress may reduce risk of a ≥2 cm breast cancer. Suppression by stress of estrogen synthesis and metabolism is a possible mechanism.     

Methionine synthase A2756G polymorphism and breast cancer risk: a meta-analysis involving 18,953 subjects

The A2756G polymorphism in the methionine synthase (MTR) gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Eleven published case–control studies, including 8,438 breast cancer cases and 10,515 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, no significant associations between the MTR A2756G polymorphism and breast cancer risk were found for GG versus AA (OR = 0.98, 95% CI: 0.84–1.15), AG versus AA (OR = 0.95, 95% CI: 0.89–1.01), GG/AG versus AA (OR = 0.95, 95% CI = 0.89–1.01), and GG versus AG/AA (OR = 1.00, 95% CI: 0.86–1.17). However, in the stratified analysis, significantly decreased breast cancer risks were found among Europeans (AG versus AA, OR = 0.90, 95% CI = 0.83–0.98; GG/AG versus AA, OR = 0.90, 95% CI = 0.82–0.97) and studies with population-based controls (AG versus AA, OR = 0.93, 95% CI = 0.86–1.00; GG/AG versus AA, OR = 0.93, 95% CI = 0.86–1.00). When stratifying by the menopausal status, no significant result was observed in all genetic models. Taken together, the results suggest that the MTR A2756G polymorphism may contribute to susceptibility to breast cancer among Europeans.     

<Emphasis Type="Italic">HER2</Emphasis> codon 655 polymorphism and breast cancer risk: a meta-analysis

To evaluate the association between HER2 codon 655 polymorphism and breast cancer risk in this meta-analysis. A comprehensive search was performed to identify all case–control studies investigating such association. Statistical analyses were conducted with software MIX 1.54. Twenty eligible reports, including 10,642 cases/11,259 controls, were identified. In overall analysis, the Val allele frequency in cases was significantly higher than that in controls (OR = 1.0921, 95% CI: 1.0013–1.191, P = 0.0466), while no associations were found in both recessive and dominant models. In subgroup analysis, HER2 codon 655 polymorphism was weakly associated with breast cancer risk in recessive (OR = 2.4624, 95% CI: 1.0619–5.7104, P = 0.0357), dominant (OR = 1.2781, 95% CI: 1.0353–1.5779, P = 0.0225), and co-dominant genetic models (OR = 1.2947, 95% CI: 1.0682–1.5693, P = 0.0085) in Asian population, respectively. Meanwhile, the susceptibility to breast cancer in people aged ≤45 was significantly increased in both recessive (OR = 2.2408; 95% CI: 1.2876–3.8998, P = 0.0043), and dominant models (OR = 1.2902, 95% CI: 1.1035–1.5085, P = 0.0014). No significant associations were observed in Caucasian, European, and Family history subgroups. So our analyses suggest HER2 codon 655 Val allele is weakly associated with an increased risk of breast cancer, and SNP at HER2 codon 655 could be considered as a susceptibility biomarker for breast cancer for Asian females or women age 45 years or younger. Weiyang Tao and Chunyang Wang contribute equally to this work.     

Relationship between diabetes and risk of second primary contralateral breast cancer

Breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer (CBC) compared to the risk of breast cancer among women in the general population. While data regarding the relationship between diabetes and breast cancer incidence are inconsistent, diabetes is more clearly linked to an elevated risk of all-cause mortality among breast cancer survivors. However, no prior studies have assessed its impact on CBC risk. We assessed the relationship between diabetes, and CBC risk in a population-based nested case–control study consisting of women 40–79 years of age diagnosed with a first primary ER-positive invasive breast cancer. It included 322 women who developed a second primary CBC and 616-matched control women diagnosed only with a first breast cancer. We used conditional logistic regression to quantify associations between diabetes and CBC risk. Compared to women without a history of diabetes, diabetics had a 2.2-fold [95% confidence interval (CI) 1.3–3.6] increased risk of CBC. This risk was more pronounced among women diagnosed with their first breast cancer before age 60 years (odds ratio, OR = 11.5, 95% CI 2.4–54.5), compared to those diagnosed at age 60 years or older (OR = 1.5, 95% CI 0.8–2.7, P for interaction = 0.011). Diabetics diagnosed with breast cancer appear to have an elevated risk of CBC. This is the first study to report this relationship, but if confirmed efforts to insure that diabetic breast cancer survivors are carefully screened for second breast cancers may be warranted.     

P53 codon 72 polymorphism contributes to breast cancer risk: a meta-analysis based on 39 case–control studies

P53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies revealing conflicting results on the role of p53 codon 72 polymorphism (G>C) on breast cancer risk led us to perform a meta-analysis to investigate this relationship. Thirty-nine published studies, including 26,041 breast cancer cases and 29,679 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results suggested that the variant genotypes were associated with a significantly reduced breast cancer risk (GC vs. GG: OR = 0.91, 95% CI: 0.83–1.00; CC/GC vs. GG: OR = 0.90, 95% CI: 0.82–0.99). In the stratified analyses, significantly decreased risks were also found among European populations (GC vs. GG: OR = 0.89, 95% CI: 0.80–0.99; CC/GC vs. GG: OR = 0.88, 95% CI: 0.80–0.98) and studies with population-based controls (GC vs. GG: OR = 0.88, 95% CI: 0.78–0.98; CC/GC vs. GG: OR = 0.87, 95% CI: 0.78–0.97). The results suggested that p53 codon 72 polymorphism may contribute to susceptibility to breast cancer, especially in Europeans. Additional well-designed large studies were required to validate this association in different populations.     

The association between IGF1 CA repeat polymorphisms and breast cancer risk: a meta-analysis

IGF-I CA repeat polymorphisms have been reported to influence the risk for breast cancer in many studies; however, the results still remains controversial and ambiguous. Therefore, to determine more precise estimations for the relationship, a meta-analysis was performed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association. A total of 9 studies including 5641 cases and 10471 controls were involved in this meta-analysis. All studies investigated the association between (CA)19 repeat polymorphism and breast cancer risk. Of those, four studies investigated the association between (CA)20 repeat polymorphism and breast cancer risk (2585 cases and 2847 controls), and three studies were for (CA)17 repeat polymorphism (2122 cases and 2225 controls). The overall odds ratio (OR) for the (CA)19 versus non-(CA)19 allele was 1.002 (95% CI 0.972–1.033). There was no suggestion of an overall effect either in recessive or dominant modeling of (CA)19 allele effects (dominant model: OR = 1.000 95% CI 0.872–1.147; recessive model: OR = 0.959 95% CI 0.888–1.036). The comparison of (CA)19 homozygosity versus non-(CA)19 homozygosity also showed no differential susceptibility to breast cancer (OR = 0.974, 95% CI 0.838–1.132). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found among premenopausal or postmenopausal women. When stratified by ethnicity, no significant association was found in all genetic models. Furthermore, there was no evidence that two other alleles associated with the risk of breast cancer (CA17 vs. non-CA17: OR = 1.165 95% CI 0.634–2.141; CA20 vs. non-CA20: OR = 1.019 95% CI 0.909–1.143). In conclusion, the current meta-analysis suggests that three IGF-I (CA) repeat polymorphisms had no association to breast cancer risk.     

Reproductive factors associated with breast cancer risk in northern Iran

Breast cancer is a common malignancy for women in most parts of the world and the incidence in Iranian women is growing. The patients are relatively younger than their western counterparts. The aim of study was to investigate the roles of reproductive factors for breast cancer in Babol. In a case–control study in Babol, we recruited a total of 100 new patients with histologically confirmed breast cancer and 200 age-matched controls selected from outpatient clinics. Demographic and reproductive factors were ascertained by in-person interview using a constructed questionnaire. Several potential confounding factors were adjusted using multiple logistic model. The adjusted odds ratio showed that having higher age at first pregnancy and abortion were associated with increased breast cancer risk (the adjusted OR = 4.1, 95% CI: 1.3–13.2 and 2.93, 95% CI: 1.64–5.24, respectively). By increasing parity, the risk had reduced significantly; among women with parity ≥5, the adjusted OR was 0.09 (95% CI 0.01–0.7) compared with nulliparous women, and also for each additional parity, the risk reduced by 50% (OR = 0.50, 95% CI: 0.34–0.71). The duration of breast feeding was inversely associated with breast cancer risk, while after additional adjustment for parity, no longer the protective effect of breast feeding was observed. Nulliparity, late age at first birth and abortion were the most important reproductive factors associated with breast cancer risk; therefore, it is recommended to women with these risk factors to perform breast cancer screening tests earlier.     

Correlation of major histocompatibility complex class I related A (MICA) polymorphism with the risk of developing breast cancer

In the present study, we examined the association of different alleles of MICA gene with the risk of breast cancer development in Iranian population. Our data showed a significant relationship between longer alleles, alleles with 9- and 6-GCT repeat of MICA gene, and a higher risk of developing breast cancer according to the age of onset. The data indicated a 6-fold increase for developing breast cancer in patients carrying the allele with 6-GCT repeat after age 50 (OR = 5.8333, 95% CI: 1.2976–26/2236, P = 0.0172). In addition, patients carrying longer alleles in their genotype (6/6, 6/9, and 9/9 genotypes) were found significantly at higher risk of developing breast cancer than control individuals (OR = 5.6, P = 0.0038, 95% CI: 1.6578–18.9166). In contrast, alleles with short GCT repeat of 4 and 5.1 showed to play a role in reducing the risk of breast cancer (OR = 0.79, P = 0.3643 and 95% CI: 0.4743–1.3157). Women with allele 4 were found twofold more protected against breast cancer (OR = 0.4597, 95% CI: 0.2164–0.9765, P = 0.0401). The results suggested that women with genotypes with 9- and 6-GCT repeat alleles of MICA gene could be considered more potent to develop breast cancer especially at higher age.     

Breastfeeding reduces breast cancer risk: a case–control study in Tunisia

In this report, we examined the relationship between mother’s breastfeeding history and her risk of breast cancer, in a case–control study in Tunisia between 2006 and 2009. About 400 breast cancer cases and 400 controls were included. Cases and controls were interviewed using a standardized structured questionnaire to obtain information on breastfeeding and other risk factors. Mean duration of breastfeeding per child was significantly associated with a reduced risk of breast cancer for women who breastfed for >24 months per child. The OR was 0.46 (95% CI, 0.28–0.76) when compared those who breastfed for <6 months. The test for trend was significant (p = 0.01). A significantly reduced risk of breast cancer was found for those whose lifetime duration of breastfeeding was 73–108 months (OR = 0.65, 95% CI, 0.36–1.18) and for those who breastfed for ≥109 months (OR = 0.42, 95% CI, 0.20–0.84). Stratification by menopausal status showed a reduced risk of breast cancer associated with a longer duration of breastfeeding for both pre- and postmenopausal women. The risk reduction was more consistent for lifetime duration of breastfeeding, the test for trend being significant for both pre- (p = 0.03) and postmenopausal (p = 0.01) women. These results support an inverse association between breastfeeding and breast cancer risk.     

Incomplete pregnancy and risk of ovarian cancer: results from two Australian case–control studies and systematic review

Although full-term pregnancies reduce the risk of ovarian cancer, it has not been conclusively established whether incomplete pregnancies also influence risk. We investigated the relationship between a history of incomplete pregnancy and incident epithelial ovarian cancer among over 4,500 women who participated in two large Australian population-based case–control studies in 1990–1993 and 2002–2005. They provided responses to detailed questions about their reproductive histories and other personal factors. Summary odds ratios (OR) and confidence intervals (CI) derived for each study using the same covariates were aggregated. We found no significant associations between the number of incomplete pregnancies and ovarian cancer, for parous (OR = 0.98, 95% CI: 0.89, 1.08) or nulliparous (OR = 1.06, 95% CI: 0.75, 1.48) women, nor for the number of spontaneous or induced abortions and ovarian cancer for parous women (OR = 0.95, 95% CI 0.82, 1.09; OR = 1.08, 95% CI: 0.86, 1.36) or nulliparous women (OR = 1.2, 95% CI: 0.6, 2.4; OR = 0.8, 95% CI: 0.47, 1.38), respectively. A systematic review of 37 previous studies of the topic confirmed our findings that a history of incomplete pregnancy does not influence a woman’s risk of epithelial ovarian cancer.     

Lack of association between the hOGG1 Ser326Cys polymorphism and breast cancer risk: evidence from 11 case–control studies

The functional Ser326Cys polymorphism in the human 8-oxogunaine DNA glycosylase (hOGG1) gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Eleven published case–control studies, including 6,804 breast cancer cases and 6,725 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, no significant associations between the hOGG1 Ser326Cys polymorphism and breast cancer risk were found for Cys/Cys versus Ser/Ser (OR = 1.07, 95% CI: 0.94–1.20), Ser/Cys versus Ser/Ser (OR = 0.99, 95% CI: 0.91–1.07), Cys/Cys + Ser/Cys versus Ser/Ser (OR = 1.00, 95% CI = 0.93–1.08), and Cys/Cys versus Ser/Cys + Ser/Ser (OR = 1.07, 95% CI: 0.97–1.18). In the stratified analysis by ethnicity, source of controls, and menopausal status, significant associations were still not observed in all genetic models. Taken together, the results suggest that the hOGG1 Ser326Cys polymorphism is not associated with breast cancer risk.     

No association between a progesterone receptor gene promoter polymorphism (+331G>A) and breast cancer risk in Caucasian women: evidence from a literature-based meta-analysis

Sex steroid hormones and their receptors such as estrogen receptor (ER) and progesterone receptor (PgR) have been widely studied for their roles in the etiology of breast cancer. To date, many studies have evaluated the association between a functional polymorphism in the PgR gene promoter (+331G>A, rs10895068) and breast cancer risk; however, the result is still ambiguous and inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was performed in this study. By searching relevant literature, a total of 10 studies containing 13,702 cases and 14,726 controls (28,428 subjects in total) were identified and meta-analyzed. All the study subjects were Caucasian women. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the codominant model, dominant model, and recessive model. Overall, no significant association between +331G>A polymorphism and breast cancer susceptibility was observed for AA versus GG (OR = 0.940, 95% CI: 0.566–1.562), GA versus GG (OR = 1.061, 95% CI: 0.888–1.267), AA + GA versus GG (OR = 1.074, 95% CI: 0.956–1.207), and AA versus GA + GG (OR = 0.951, 95% CI: 0.586–1.544). Sensitivity analysis was performed by limiting the meta-analysis to those studies fulfilling Hardy–Weinberg equilibrium, and the results were not materially altered in any genetic model. In conclusion, the present meta-analysis strongly suggests that +331G>A in the PgR gene is not associated with breast cancer risk.     

Soy intake in association with menopausal symptoms during the first 6 and 36 months after breast cancer diagnosis

It has been suggested that soy food and its components may relieve menopausal symptoms (MPS) including hot flashes, night sweats, and vaginal dryness in healthy women. However, little is known about the effect of soy food intake on MPS in women with breast cancer. We examined associations of occurrence of MPS with soy food intake in 4,842 Chinese women aged 20–75 years who had non-metastatic breast cancer and had not used hormone replacement therapy. MPS were assessed at 6 and 36 months after cancer diagnosis using a standardized questionnaire, and associations with soy food intake were evaluated in multivariate regression analyses. Daily soy food intake was assessed at 6 months postdiagnosis and over the first 36 months postdiagnosis using a validated food frequency questionnaire. The prevalence of MPS was 56% at 6 months and 63% at 36 months postdiagnosis with the hotflash being the most common MPS (~44–55%). Hot flashes occurred mainly in premenopausal breast cancer patients who were in the highest quartile of isoflavone intake at 6 months postdiagnosis (OR = 1.20, 95% CI: 0.98–1.59) compared with the lowest quartile. This association was stronger at 36 months postdiagnosis (OR = 1.59, 95% CI: 1.02–2.48). We found no significant associations for any MPS, night sweats, or vaginal dryness. Neither tamoxifen use nor BMI modified the association between MPS and isoflavone intake. There was no evidence that soy food consumption reduced MPS among breast cancer patients. High soy intake may increase the prevalence of hotflashes among premenopausal patients. Our study suggests that soy acts as an estrogen antagonist in breast cancer patients.     

Current evidences on XPC polymorphisms and breast cancer susceptibility: a meta-analysis

Published data on the association between three polymorphisms (Lys939Gln, Ala499Val, and PAT±) of Xeroderma Pigmentosum group C (XPC) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 11 studies including 5,090 cases and 5,214 controls were involved in this meta-analysis. For XPC Lys939Gln polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR = 1.00, 95% CI 0.92–1.10; Gln/Gln vs. Lys/Lys: OR = 0.96, 95% CI 0.84–1.09; dominant model: OR = 0.99, 95% CI 0.91–1.08; and recessive model: OR = 0.97, 95% CI 0.86–1.09). In the subgroup analysis by ethnicity or study design, still no obvious associations were found. For XPC Ala499Val polymorphism, also no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Val/Ala vs. Ala/Ala: OR = 0.91, 95% CI 0.79–1.05; Val/Val vs. Ala/Ala: OR = 1.07, 95% CI 0.80–1.44; dominant model: OR = 0.93, 95% CI 0.81–1.06; and recessive model: OR = 1.11, 95% CI 0.84–1.48). For XPC PAT± polymorphism, obvious associations were found for recessive model when all studies were pooled into the meta-analysis (OR = 1.41, 95% CI 1.05–1.89). In conclusion, this meta-analysis suggests that the XPC PAT± polymorphism allele may be a low-penetrant risk factor for developing breast cancer.