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.     

Perceived risk of breast cancer among Latinas attending community clinics: risk comprehension and relationship with mammography adherence

Objective  To describe breast cancer risk perceptions, determine risk comprehension, and evaluate mammography adherence among Latinas. Methods  Latina women age ≥35, primarily from Central and South America, were recruited from community-based clinics to complete in-person interviews (n = 450). Risk comprehension was calculated as the difference between numeric perceived risk and Gail risk score. Based on recommended guidelines from the year data were collected (2002), mammography adherence was defined as having a mammogram every one to two years for women ≥40 years of age. Results  Breast cancer risk comprehension was low, as 81% of women overestimated their risk and only 6.9% of women were high risk based on Gail risk scores. Greater cancer worry and younger age were significantly associated with greater perceived risk and risk overestimation. Of women age eligible for mammography (n = 328), 29.0% were non-adherent to screening guidelines. Adherence was associated with older age, (OR = 2.99, 95% CI = 1.76–5.09), having insurance (OR = 1.81, 95% CI = 1.03–3.17), greater acculturation (OR = 1.18, 95% CI = 1.02–1.36), and higher breast cancer knowledge (OR = 2.03, 95% CI = 1.21–3.40). Conclusions  While most Latinas over-estimated their breast cancer risk, older age, having insurance, being more acculturated, and having greater knowledge were associated with greater screening adherence in this Latino population. Perceived risk, risk comprehension, and cancer worry were not associated with adherence. In Latinas, screening interventions should emphasize knowledge and target education efforts at younger, uninsured, and less acculturated mammography-eligible women. Supported by Grants U01CA86114, U01CA114593, K05CA96940 (JM), and K07CA131172 (KG) from the National Cancer Institute.     

Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White women

Purpose Lymphedema of the arm is a potential complication of breast cancer therapy. This study examines pre-disposing factors that may operate in conjunction with treatment-related factors in the development of arm lymphedema in a large cohort of White and Black breast cancer survivors. Methods 494 women (271 White and 223 Black) with in situ to Stage III-A primary breast cancer completed a baseline interview within 18 months of diagnosis. Information on lymphedema was collected during a follow-up interview, conducted on average 50 months after diagnosis. Self-reported data were used to classify women with or without lymphedema. Multivariable logistic regression models were developed to identify risk factors for arm lymphedema. Results Arm lymphedema was associated with younger age at diagnosis (odds ratio, OR per year of age = 0.96; 95% confidence interval, CI = 0.93–0.99), positive history of hypertension (OR = 2.31; 95% CI = 1.38–3.88), obesity (OR for body mass index, BMI≥30 = 2.48; 95% CI = 1.05–5.84) and having had surgery where 10 or more lymph nodes were excised (OR = 2.16; 95% CI = 1.12–4.17). While Black women had higher prevalence of arm lymphedema than White women (28% vs. 21%), race was not associated with lymphedema risk in models adjusted for multiple factors (adjusted OR = 1.01; 95% CI = 0.63–1.63). Conclusion Risk of arm lymphedema did not differ significantly for Black and White women. Risk factors identified in this study offer opportunities for interventions (weight loss, control of blood pressure, use of sentinel node biopsy where possible) for reducing incidence of lymphedema or controlling the symptoms associated with this condition.     

Current evidence on the relationship between HRAS1 polymorphism and breast cancer risk: a meta-analysis

Several molecular epidemiological studies were conducted in recent years to evaluate the association between NQO1 Pro187Ser polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on 3177 cases with breast cancer and 4038 controls from seven published case–control studies showed that the 187Ser allele was not associated with a significantly increased risk of breast cancer (Ser versus Pro: P = 0.33, OR = 1.08, 95% CI = 0.92–1.28; Ser/Ser versus Pro/Pro: P = 0.58, OR = 1.16, 95% CI = 0.68–2.00; Ser/Ser versus Pro/Ser + Pro/Pro: P = 0.62, OR = 1.14, 95% CI = 0.68–1.90; Ser/Ser + Pro/Ser versus Pro/Pro: P = 0.30, OR = 1.07, 95% CI = 0.94–1.22). In the stratified analysis by ethnicity, we found that the Pro187Ser polymorphism was associated with increased breast cancer risk in Caucasians in the additive genetic model and dominant genetic model (P = 0.03, OR = 1.13, 95% CI = 1.01–1.26; P = 0.03, OR = 1.15, 95% CI = 1.01–1.30, respectively), whereas no significant in Asians (P = 0.44, OR = 0.94, 95% CI = 0.80–1.10) and postmenopausal women (P = 0.99, OR = 1.00, 95% CI = 0.84–1.19). The results suggest that NQO1 Pro187Ser polymorphism may contribute to breast cancer development in Caucasians.     

Diabetes and risk of pancreatic cancer: a pooled analysis of three large case–control studies

Racial differences in diabetes-associated pancreatic cancer (PC) and the interaction of diabetes with other risk factors are not well established. We determined the association between diabetes and risk of PC in 2,192 cases and 5,113 controls in three large case–control studies conducted at the National Cancer Institute, the University of California San Francisco, and the M.D. Anderson Cancer Center. In multivariable analyses, diabetes was associated with a 1.8-fold risk of PC [95% confidence interval (CI) = 1.5–2.1]. Risk estimates decreased with increasing years with diabetes (≤2 years OR = 2.9, 95% CI = 2.1–3.9; 3–5 years OR = 1.9, 95% CI = 1.3–2.6; 6–10 years OR = 1.6, 95% CI = 1.2–2.3; 11–15 years OR = 1.3, 95% CI = 0.9–2.0; > 15 years OR = 1.4, 95% CI = 1.0–2.0 (p for trend < 0.0001). Among diabetics, risk was higher in insulin ever users compared with nonusers (OR = 2.2, 95% CI = 1.6–3.7) and was restricted to insulin use of ≤3 years (OR = 2.4). Insulin use of >10 years was associated with a reduced risk of pancreatic cancer (OR = 0.5, 95% CI = 0.3–0.9; p for trend < 0.0001). Hispanic men and Asians had a higher risk of diabetes-associated PC than did whites and blacks, but the differences were not statistically significant. No significant interaction between diabetes and cigarette smoking, alcohol consumption and body mass index was observed. Although reverse causation may explain the association between diabetes diagnosed in close temporal proximity to PC, our results show that long-term diabetes, even though risk diminishes over time, remains a risk factor for PC independent of obesity and smoking.     

Risk of pancreatic cancer by alcohol dose,duration, and pattern of consumption,including binge drinking: a population-based study

Alcohol consumption is postulated to be a risk factor for pancreatic cancer (PCA), but clarification of degree of risk related to consumption characteristics is lacking. We examined the association between alcohol consumption and PCA in a population-based case–control study (532 cases, 1,701 controls) in the San Francisco Bay Area. Population-based controls were frequency-matched by sex, age within 5-year categories and county of residence to cases identified by the cancer registry’s rapid case ascertainment. Detailed alcohol consumption data, including binge drinking (≥5 drinks/day), were collected during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed using adjusted unconditional logistic regression. Depending on dose, duration, and pattern of drinking, ORs were increased 1.5- to 6-fold among men but not women. In men, ORs increased with increasing overall alcohol consumption (22–35 drinks/week OR = 2.2, 95% CI = 1.1–4.0; ≥35 drinks/week OR = 2.6, 95% CI = 1.3–5.1, p-trend = 0.04). Most notable were effects with a history of binge drinking (OR = 3.5, 95% CI = 1.6–7.5) including increased number of drinks per day (p-trend = 0.002), and increased years of binge drinking (p-trend = 0.0006). In fully adjusted models that included smoking and other confounders, ORs for binge drinking in men were somewhat higher than in age-adjusted models. Results from our detailed analyses provide support for heavy alcohol consumption (including binge drinking) as a risk factor for PCA in men.     

IGFBP3 A-202C polymorphism and breast cancer susceptibility: a meta-analysis involving 33,557 cases and 45,254 controls

Published data on the association between insulin-like growth factor binding protein 3 (IGFBP3) A-202C polymorphism 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 27 studies including 33,557 cases and 45,254 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with IGFBP3 C allele when all studies were pooled into the meta-analysis (CC vs. AA: OR = 1.06, 95% CI = 1.02–1.11; dominant model: OR = 1.04, 95% CI = 1.00–1.07). In the subgroup analysis by ethnicity, significantly increased risk was found for Caucasians (AC vs. AA: OR = 1.04, 95% CI = 1.00–1.08; CC vs. AA: OR = 1.05, 95% CI = 1.01–1.10; dominant model: OR = 1.04, 95% CI = 1.00–1.08) and Asians (CC vs. AA: OR = 1.35, 95% CI = 1.02–1.78; recessive model: OR = 1.38, 95% CI = 1.05–1.82). When stratified by study design, statistically significantly elevated risk was found among population-based studies (CC vs. AA: OR = 1.06, 95% CI = 1.01–1.11; dominant model: OR = 1.03, 95% CI = 1.00–1.07). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found among premenopausal or postmenopausal women. In conclusion, this meta-analysis suggests that the IGFBP3 C allele is a low-penetrant risk factor for developing breast cancer.     

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..     

Physical activity, sedentary behavior, and the risk of colon and rectal cancer in the NIH-AARP Diet and Health Study

Objective  In order to prospectively investigate physical activity at varying intensities and sedentary behavior in relation to colorectal cancer. Methods  We considered 488,720 participants of the NIH-AARP Diet and Health Study who were aged 50–71 years at baseline in 1995–1996. Through 31 December, 2003, we identified 3,240 and 1,482 colorectal cancers among men and women, respectively. We estimated multivariable relative risks (RR) and 95% confidence intervals (CI) of colorectal cancer using Cox regression. Results  Engaging in exercise/sports five or more times per week compared to never or rarely exercising was associated with a reduced risk of colon cancer among men (p = 0.001; RR = 0.79, 95% CI = 0.68–0.91) and a suggestive decrease in risk among women (p = 0.376; RR = 0.85, 95% CI = 0.70–1.04). Engaging in exercise/sports was also associated with a decreased risk of rectal cancer in men (P = 0.074; RR comparing extreme categories = 0.76, 95% CI = 0.61–0.94). In men, we observed inverse relations of both low intensity (p = 0.017; RR = 0.81, 95% CI = 0.65–1.00 for ≥7 h/week) and moderate to vigorous intensity activity (p = 0.037; RR = 0.82, 95% CI = 0.67–0.99 for ≥7 h/week) to colon cancer risk. In contrast, sedentary behavior (time spent watching television/videos) was positively associated with colon cancer (p < 0.001; RR = 1.61, 95% CI = 1.14–2.27 for ≥9 h/day) among men. Similar, but less pronounced relations were observed in women. Conclusion  Engaging in physical activity of any intensity is associated with reductions in colon and rectal cancer risk. Conversely, time spent sedentary is associated with increased colon cancer risk.     

The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis

It was reported that the functional polymorphism Ser326Cys in the human 8-oxoguanine DNA glycosylase gene was associated with breast cancer risk; however, the published studies have inconsistent conclusions. To elucidate the effect of hOGG1 Ser326Cys on the susceptibility to breast cancer, all available studies were collected in this meta-analysis. We extracted the data from 10 case–control studies that were published in the PubMed database from 2003 to 2008 using the search phrases “human 8-oxoguanine DNA glycosylase, hOGG1, OGG1, OGG, polymorphism, genetic variation, and breast cancer.” This meta-analysis included 4,963 breast cancer cases and 4,776 control subjects. The results showed that individuals who carrying the hOGG1 326Cys allele in the additive model did not have significantly increased risk of breast cancer compared with those carrying the 326Ser allele (P = 0.47, OR = 1.02; 95% CI = 0.96–1.09); similarly, no significant association between the hOGG1 326Cys allele and breast cancer risk was found either in the recessive genetic model (P = 0.34, OR = 1.06; 95% CI = 0.94–1.18) for Cys/Cys versus Ser/Cys + Ser/Ser, or dominant genetic model (P = 0.78, OR = 1.01; 95% CI = 0.93–1.11) for Cys/Cys + Ser/Cys versus Ser/Ser. In the stratified analysis, the meta-analysis showed the association between hOGG1 326Cys allele in the additive model and breast cancer was significant in European subjects (P = 0.04, OR = 0.71; 95% CI = 0.51–0.98), and dominant genetic model (P = 0.004, OR = 0.44; 95% CI = 0.25–0.77). However, the association was not significant between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (Asians and Americans). The meta-analysis suggested that the hOGG1 326Cys allele plays a significant protective effect to breast cancer in European women.     

<Emphasis Type="Italic">MDM2</Emphasis> 309 T/G polymorphism is associated with colorectal cancer risk especially in Asians: a meta-analysis

The murine double minute 2 (MDM2) gene encodes an important regulator which mainly functions as an E3 ligase. The role of the MDM2 protein in the P53 pathway has been especially well-studied. In this study, our aim was to explore the relationship between MDM2 gene 309 T/G polymorphism and colorectal cancer risk. Performing both the overall meta-analysis and the subgroup meta-analysis based on ethnicity and source of controls with a total of 7 eligible studies (2,543 cases and 2,115 controls in all), we detected a significant colorectal cancer risk variation for TG versus GG (OR = 0.73, 95% CI = 0.62–0.86) in the overall analysis and another significant colorectal cancer risk variation for TG versus GG (OR = 0.70, 95% CI = 0.59–0.83) in the population-based controls’ subgroup as well. Moreover, in the subgroup analysis based on ethnicity, significant associations were observed for all genetic models in Asians (OR = 0.51, 95% CI = 0.41–0.64 for TT versus GG; OR = 0.64, 95% CI = 0.53–0.78 for TG versus GG; OR = 0.59, 95% CI = 0.49–0.71 for dominant model; OR = 0.69, 95% CI = 0.57–0.82 for recessive model), while in Caucasians there was no obvious association. In summary, according to the results of our meta-analysis, the MDM2 309 G allele probably acts as a colorectal cancer risk factor, especially in Asians.     

The association of SULT1A1 codon 213 polymorphism and breast cancer susceptibility: meta-analysis from 16 studies involving 23,445 subjects

Epidemiological studies on the association between SULT1A1 codon 213 polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was conducted in this article. Sixteen studies including 9,881 cases and 13,564 controls were collected for SULT1A1 codon 213 polymorphism by searching the databases of Medline, PubMed, Embase, and ISI Web of Knowledge. The strength of association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 21 studies were pooled into the meta-analysis, there was no evidence for significant association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility (for Arg/Arg versus Arg/His: OR = 0.999, 95% CI = 0.941–1.061; for Arg/Arg versus His/His: OR = 1.121, 95% CI = 1.013–1.242; for dominant model: OR = 1.128, 95% CI = 1.01–1.26; for recessive model: OR = 1.151, 95% CI = 0.950–1.394). In the subgroup analysis by the source of controls, significant increased risk was found for hospital-based studies (for Arg/Arg versus Arg/His: OR = 1.173, 95% CI = 1.000–1.376; for Arg/Arg versus His/His: OR = 1.600, 95% CI = 1.134–2.256; for dominant model: OR = 1.269, 95% CI = 1.134–2.256; for recessive model: OR = 1.664, 95% CI = 1.070–2.588). In summary, the meta-analysis suggests that SULT1A1 codon 213 polymorphism may be associated with the hospital-based studies. However, large number of samples and representative hospital-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.     

Birth weight and other prenatal factors and risk of breast cancer in Asian-Americans

Little is known about the role of birth weight and other prenatal factors in the etiology of breast cancer in Asian-Americans. We investigated the relation between birth weight and other prenatal factors and breast cancer risk in a population-based case–control study in Los Angeles County that included 2,259 Asian-American women with incident, histologically confirmed breast cancer and 2,019 control women, who were frequency matched to cases on age, Asian ethnicity, and neighborhood of residence. Breast cancer risk nearly doubled (odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.15–3.39) among those with high (≥4000 g) birth weight compared to those with low (<2500 g) birth weight after adjusting for age at menarche, parity, adult body mass index, and other covariates. Risk increased 8% per 500 g increase in birth weight (P trend = 0.10). We observed a significant relationship between birth weight and age at menarche in both cases and controls. Mean birth weight was higher (2948 g) for control women who had early menarche (age ≤ 11 years) compared to those who had menarche late (age ≥ 15 years) (2807 g) (P trend = 0.016); results were similar among case patients (P trend = 0.020). Older maternal age was also a risk factor; risk increased by 6% (95% CI = 1.01–1.12) per 5 years increase in maternal age with adjustment for parity and other risk factors. Our results support the hypothesis that high birth weight and older maternal age at pregnancy may have contributed to the rising breast cancer incidence in Asian-Americans.     

HER2 Ile655Val polymorphism contributes to breast cancer risk: evidence from 27 case–control studies

Proto-oncogene HER2 (also known as erbB-2 or neu) plays an important role in the carcinogenesis and the prognosis of breast cancer. Many epidemiological studies have been conducted to explore the association between the HER2 Ile655Val polymorphism and breast cancer risk. However, inconsistency existed in the results. Therefore, we performed a meta-analysis of 27 published case–control studies including 11,504 cases and 12,538 controls. We assessed the strength of the association by crude odds ratios (ORs) with 95% confidence intervals (CIs) and reached a result that HER2 Ile655Val polymorphism was associated with an increased breast cancer risk in overall populations (for Ile/Val vs. Ile/Ile: OR = 1.05, 95% CI = 1.00–1.12, P = 0.07 for heterogeneity; for the dominant model Ile/Val + Val/Val vs. Ile/Ile: OR = 1.10, 95% CI = 1.01–1.20, P = 0.01 for heterogeneity). In subgroup analysis by ethnicity, we found a significant association among Africans (for Val/Val vs. Ile/Ile: OR = 8.78, 95% CI = 1.94–39.72, P = 0.35 for heterogeneity; for the recessive model Val/Val vs. Ile/Val +Ile/Ile: OR = 8.60, 95% CI = 1.92–38.48, P = 0.31 for heterogeneity) and Asians (for Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01–1.39, P = 0.41 for heterogeneity; for the dominant model Val/Val + Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01–1.38, P = 0.27 for heterogeneity). In conclusion, our meta-analysis suggests that HER2 Ile 655Val polymorphism may contribute to breast cancer risk.     

The association between two polymorphisms of eNOS and breast cancer risk: a meta-analysis

Breast cancer is one of the most common malignant tumors worldwide. Endothelial nitric oxide synthase (eNOS) plays a key role in breast cancer development. The associations between the two eNOS polymorphisms (E298D rs1799983, −786T>C rs2070744) and breast cancer risk are inconclusive. A meta-analysis was performed in this study. By searching Medline, ISI Web of Knowledge, ScienceDirect, EBSCO, CNKI, and SinoMed database, six case–control studies were collected for the eNOS E298D polymorphism (3,038 cases and 2,508 controls) and three case–control studies were eligible for the eNOS −786T>C polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between the two eNOS polymorphisms and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Overall, significantly decreased risk was observed for E298D (for EE vs. DD: OR = 0.74, 95% CI = 0.59–0.94; for ED vs. DD: OR = 0.78, 95% CI = 0.61–0.98; for dominant model: OR = 0.77, 95% CI = 0.61–0.96) and −786T > C (for TT vs. CC: OR = 0.60, 95% CI = 0.42–0.86; for dominant model: OR = 0.66, 95% CI = 0.47–0.94). In the subgroup analysis by ethnicity, significant decreased risks were found for E298D (for EE vs. DD: OR = 0.75, 95% CI = 0.56–0.99) and −786T>C (for TT vs. CC: OR = 0.53, 95% CI = 0.35–0.81; for dominant model: OR = 0.61, 95% CI = 0.41–0.91; for recessive model: OR = 0.70, 95% CI = 0.55–0.91) among Caucasians; significant decreased risks were observed for E298D (for ED vs. DD: OR = 0.12, 95% CI = 0.02–0.96; for dominant model: OR = 0.13, 95% CI = 0.02–1.00) among Asians. In conclusion, this meta-analysis suggests that both eNOS E298D and −786T>C polymorphisms are associated with reduced breast cancer risk.     

Association between <Emphasis Type="Italic">EGF</Emphasis> promoter polymorphisms and cancer risk: a meta-analysis

EGF promoter polymorphisms are observed to modulate EGF levels and thought to have effect on susceptibility to various carcinomas but the results are inconsistent. In this meta-analysis, we assessed published studies of the association between three EGF polymorphisms and cancer risk from 21 studies with 14,609 subjects for EGF G61A, from two studies with 2,535 subjects for G-1380A and A-1744G, respectively. For EGF G61A, the contrast of homozygote (OR = 0.80, 95% CI = 0.65–0.98), allele (OR = 0.90, 95% CI = 0.81–0.99) and dominant model (OR = 0.86, 95% CI = 0.74–0.99) produced significant association among 21 studies with relatively large heterogeneity (P _{heterogeneity} < 0.001). Through the stratified analysis, heterogeneity decreased significantly. In the stratified analysis by racial descent, the significant risks were found among Asians for homozygote contrast (OR = 0.83, 95% CI = 0.69–0.99, P _{heterogeneity} = 0.506) and Americans for the contrast of homozygote (OR = 0.50, 95% CI = 0.30–0.84, P _{heterogeneity} = 0.051), allele (OR = 0.70, 95% CI = 0.51–0.96, P _{heterogeneity} = 0.008) and dominant model (OR = 0.57, 95% CI = 0.42–0.77, P _{heterogeneity} = 0.28). No significant associations were found in all Caucasians genetic models. In the subgroup analyses by cancer types, for gastric cancer and esophageal cancer significant associations were found in all genetic models without heterogeneity. Significant risk was also found in the contrast of homozygote (OR = 0.41, 95% CI = 0.20–0.81, P _{heterogeneity} = 0.184) and recessive model (OR = 0.53, 95% CI = 0.33–0.85, P _{heterogeneity} = 0.384) for hepatoma and recessive model (OR = 0.72, 95% CI = 0.53–0.99, P _{heterogeneity} = 0.474) for glioma. For EGF G-1380A and A-1744G, no significant associations were found in all genetic models. This meta-analysis suggests that the EGF G61A polymorphism most likely contributes to decreased susceptibility to cancers among Asians and Americans, and A allele may be a protective factor for gastric cancer, esophageal cancer, hepatoma and glioma. Both EGF G-1380A and A-1744G is marginally associated with cancer susceptibility.     

MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls

Published data on the association between MTHFR C677T polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR C677T polymorphism and breast cancer risk. The pooled ORs were performed with co-dominant model (CT vs. CC, TT vs. CC), dominant model (CT + TT vs. CC), and recessive model (TT vs. CC + CT), respectively. A total of 37 studies including 15,260 cases and 20,411 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TT variant genotype in homozygote comparison and dominant genetic model when all studies were pooled into the meta-analysis (TT vs. CC: OR = 1.11, 95% CI = 1.01–1.23; dominant model: OR = 1.04, 95% CI = 1.00–1.09). In the subgroup analysis by ethnicity, significantly increased risks were found for TT allele carriers among Asians (TT vs. CC: OR = 1.18, 95% CI = 1.04–1.35; recessive model: OR = 1.15, 95% CI = 1.03–1.29). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TT vs. CC: OR = 1.18, 95% CI = 1.02–1.38; recessive model: OR = 1.17, 95% CI = 1.05–1.29). In the subgroup analysis by menopausal status, statistically significantly increased risk was found among postmenopausal women (CT vs. CC: OR = 1.12, 95% CI = 1.02–1.23; dominant model: OR = 1.11, 95% CI = 1.01–1.22). In conclusion, this meta-analysis suggests that the MTHFR T allele is a low-penetrant risk factor for developing breast cancer.     

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.     

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.     

CCND1 G870A polymorphism and risk for head and neck cancer: a meta-analysis

CCND1 plays a critical role in cell cycle control and may contribute to head and neck cancer. We performed a meta-analysis of eleven case–control studies that examined the association between CCND1 G870A polymorphism and head and neck cancer risk. Overall, no significant association of this polymorphism with head and neck cancer was found (for AA vs. GG: OR = 0.96, 95% CI = 0.59–1.58, P < 0.01 for heterogeneity; for GA vs. GG: OR = 1.00, 95% CI = 0.74–1.35, P < 0.01 for heterogeneity; for the dominant model GA/AA vs. GG: OR = 0.98, 95% CI = 0.69–1.39, P < 0.01 for heterogeneity; for the recessive model AA vs. GG/GA: OR = 0.94, 95% CI = 0.66–1.33, P < 0.01 for heterogeneity). In subgroup analysis by ethnicity, we also did not find any significant association in European and Asians populations. All the results were not materially altered in any genetic model after the studies which did not fulfill Hardy–Weinberg equilibrium were excluded. In conclusion, our meta-analysis strongly suggested that the CCND1 G870A polymorphism is not associated with head and neck cancer risk.