BCL-2 (-938C>A), BAX (-248G>A), and HER2 Ile655Val Polymorphisms and Breast Cancer Risk in Indian Population

Breast cancer is the most common carcinoma in women worldwide. The present case-control study was aimed to examine the association of BCL-2 (-938C> A), BAX (-248G > A), and HER2 (I655V i.e. A > G) polymorphisms with breast cancer risk in Indian population. This study enrolled 117 breast cancer cases and 104 controls. BCL-2 (-938C > A), BAX (-248G > A), and HER2 Ile655Val polymorphisms were screened by PCR-RFLP method. There was no significance difference in the allelic and genotype frequency of the BCL-2 (-938C > A) and BAX (-248G > A) polymorphisms between cases and controls. In relation to HER2 Ile655Val polymorphism, the statistical analysis of observed genotypic frequencies showed significant association ( p -0.0059). Compared to Ile/Ile (A/A) genotype, frequency of Ile/Val (A/G) genotype was significantly higher among cases than in control group and observed to increase the breast cancer risk (OR, 2.43; 95%CI, 1.32–4.46; p -0.004). The frequency of Val (G) allele was significantly higher in cases as compared to controls (6.83% vs 2.88%, resp.). Compared to Ile (A) allele, significant increase in the risk of breast cancer was observed with Val (G) allele (OR, 2.21; 95% CI, 1.35–3.63; p -0.0016). We observed significant association between HER2 Ile655Val polymorphism and breast cancer risk under the dominant (OR = 2.52; 95% CI: 1.41–4.51; p -0.001) and codominant (OR, 2.24; 95% CI: 1.23–4.09; p-0.008) model. In our study, BCL-2 (-938C > A) and BAX (-248G > A) polymorphism were not found to be associated with breast cancer risk. This present study for the first time shows significant association of HER2 Ile655Val polymorphism with risk of breast cancer in Indian population. Therefore, we suggest that each population need to evaluate its own genetic profile for breast cancer risk that may be helpful for better understanding the racial and geographic differences reported for breast cancer incidence and mortality.

Download Full-text

Microsatellite polymorphism in the EGFR, NOTCH4 and E2F4 genes and their association with breast cancer risk

The International Journal of Biological Markers ◽

10.5301/jbm.2012.9583 ◽

2012 ◽

Vol 27 (3) ◽

pp. 219-226 ◽

Cited By ~ 1

Author(s):

Ana González-Hernández ◽

Luis Alberto Henríquez-Hernández ◽

Antonio Cabrera De León ◽

M. del Cristo Rodríguez-Pérez ◽

Adolfo Murias-Rosales ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Cancer Risk ◽

General Population ◽

Cancer Risk ◽

Control Sample ◽

Control Group ◽

Polymorphic Microsatellites ◽

Human Genes ◽

Allelic Distribution

Background The sequences of many human genes that encode proteins involved in cancer contain polymorphic microsatellites. Variations in microsatellite length may constitute risk factors in several human diseases, a possibility that has been little explored in breast cancer. Among the genes that contain polymorphic microsatellites are EGFR, NOTCH4 and E2F4. The length of some of these microsatellites has been associated with breast cancer risk. Purpose and methods To determine whether the length of the microsatellites (CA)n in EGFR, (CTG)n in NOTCH4 and (AGC)n in E2F4 was associated with breast cancer risk, we genotyped these 3 microsatellites in 212 women with breast cancer and a control group of 308 women from the general population who did not have this disease. Results and conclusions The allelic distribution observed for the 3 microsatellites matched that found in other white populations, with the exception of some (AGC)n alleles in E2F4, which have not been described previously. The length of (CA)n in EGFR and (CTG)n in NOTCH4 was not associated with breast cancer (OR=0.99; 95% CI 0.59–1.37; p=0.619 and OR=1.08; 95% CI 0.71–1.65; p=0.725, respectively). Short alleles (<13 repeats) of (AGC)n in E2F4 were less frequent in women with cancer than in the control sample.

Download Full-text

Cabbage and Sauerkraut Consumption in Adolescence and Adulthood and Breast Cancer Risk among US-Resident Polish Migrant Women

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182010795 ◽

2021 ◽

Vol 18 (20) ◽

pp. 10795

Author(s):

Dorothy Rybaczyk Pathak ◽

Aryeh D. Stein ◽

Jian-Ping He ◽

Mary M. Noel ◽

Larry Hembroff ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Vegetable Intake ◽

Conditional Logistic Regression ◽

The United States ◽

Population Based ◽

Cook County ◽

Migrant Women ◽

Incidence And Mortality

Background: Breast cancer (BC) incidence and mortality are lower in Poland than in the United States (US). However, Polish-born migrant women to US approach the higher BC mortality rates of US women. We evaluated the association between consumption of cabbage/sauerkraut foods and BC risk in Polish-born migrants to US. Methods: We conducted a case–control study of BC among Polish-born migrants in Cook County and the Detroit Metropolitan Area. Cases (n = 131) were 20–79 years old with histological/cytological confirmation of invasive BC. Population-based controls (n = 284) were frequency matched to cases on age and residence. Food frequency questionnaires assessed diet during adulthood and age 12–13 years. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated with conditional logistic regression. Consumption of total, raw/short-cooked, and long-cooked cabbage/sauerkraut foods was categorized as low, medium, or high (frequency of servings/week). Results: Higher consumption of total and raw/short-cooked cabbage/sauerkraut foods, during both adolescence and adulthood, was associated with a significantly lower BC risk. Consumption of long-cooked cabbage/sauerkraut foods was low and not significantly associated with risk. The multivariate OR for total cabbage/sauerkraut consumption, high vs. low (> 4 vs. ≤ 2 servings/week) during adolescence was 0.36 (95% CI = 0.18–0.71, ptrend < 0.01) and 0.50 (95% CI = 0.23–1.06, ptrend = 0.08) during adulthood. For raw/short-cooked cabbage/sauerkraut (>3 vs. ≤1.5 servings/week), the ORs were 0.35 (95% CI = 0.16–0.72, ptrend < 0.01) during adolescence and 0.37 (95% CI = 0.17–0.78, ptrend < 0.01) during adulthood. For joint adolescent/adult consumption of raw/short-cooked cabbage/sauerkraut foods, (high, high) vs. (low, low), the OR was 0.23 (95% CI = 0.07–0.65). The significant association for high adolescent consumption of raw/short-cooked cabbage/sauerkraut foods and reduced BC risk was consistent across all levels of consumption in adulthood. Conclusion: Greater consumption of total and raw/short-cooked cabbage/sauerkraut foods either during adolescence or adulthood was associated with significantly reduced BC risk among Polish migrant women. These findings contribute to the growing literature suggesting a protective effect of a potentially modifiable factor, cruciferous vegetable intake, on breast cancer risk.

Download Full-text

Aromatase and breast cancer susceptibility.

Endocrine Related Cancer ◽

10.1677/erc.0.0060165 ◽

1999 ◽

pp. 165-173 ◽

Cited By ~ 108

Author(s):

N M Probst-Hensch ◽

S A Ingles ◽

A T Diep ◽

R W Haile ◽

F Z Stanczyk ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Incidence ◽

Breast Cancer Incidence ◽

Latina Women ◽

Repeat Polymorphism ◽

Cyp19 Gene ◽

Functional Relevance

Based on experimental and epidemiological evidence it is hypothesized that estrogen increases breast cancer risk by increasing mitotic activity in breast epithelial cells. Aromatase is crucial to the biosynthesis of estrogens and may therefore play a role in breast cancer development. Supporting data for an etiological role of aromatase in breast tumor biology are several-fold. First, the association between weight and postmenopausal breast cancer risk may be mediated by aromatase. Secondly, a pilot study found a higher aromatase expression in normal breast adipose tissue from breast cancer cases as opposed to healthy women. Thirdly, experimental data in animals suggest that aromatase activity predisposes mammary tissue to preneoplastic and neoplastic changes. In a multiethnic cohort study conducted in Los Angeles and on Hawaii we investigated (i) whether the plasma estrone to androstenedione (E1/A) ratio in different ethnic groups was associated with ethnic differences in breast cancer incidence, and (ii) whether genetic variation in the CYP19 gene encoding the P450 aromatase protein was associated with breast cancer risk. The age- and weight-adjusted ethnic specific E1/A ratios x 100 among women without oophorectomy were 7.92 in African-Americans, 8.22 in Japanese, 10.73 in Latinas and 9.29 in non-Latina Whites (P=0.09). The high E1/A ratio in Latina women was not associated with a high breast cancer incidence; in fact Latina women had the lowest breast cancer incidence in the cohort observed so far. We found no consistent association of an intronic (TTTA)n repeat polymorphism with breast cancer risk in different ethnic groups. This polymorphism was not associated with differences in the plasma E1/A ratio in a way that would predict its functional relevance. We describe a newly identified TTC deletion in intron 5 of the CYP19 gene that is associated with the (TTTA)n repeat polymorphism. Neither this polymorphism, nor a polymorphism at codon 264 in exon VII of the CYP19 gene, was associated with breast cancer. We did not identify any genetic variation in exon VIII in 54 African-American subjects. We identified rare genetic variants of unknown functional relevance in the promoter 1.4 of the CYP19 gene in 3 out of 24 Latina women. Further investigation into the role of aromatase in breast cancer etiology is important, given that the potential use of aromatase inhibitors as breast cancer chemopreventives depends on these results.

Download Full-text

Could Recent Decreases in Breast Cancer Incidence Really Be Due to Lower HRT Use? Trends in Attributable Risk for Modifiable Breast Cancer Risk Factors in Canadian Women

Can J Public Health ◽

10.1007/bf03404862 ◽

2010 ◽

Vol 101 (5) ◽

pp. 405-409 ◽

Cited By ~ 18

Author(s):

C. Ineke Neutel ◽

Howard Morrison

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Incidence ◽

Breast Cancer Incidence ◽

Attributable Risk ◽

Cancer Risk Factors ◽

Breast Cancer Risk Factors

Download Full-text

Sleep duration and breast cancer incidence: results from the Million Women Study and meta-analysis of published prospective studies

SLEEP ◽

10.1093/sleep/zsaa166 ◽

2020 ◽

Author(s):

Angel T Y Wong ◽

Alicia K Heath ◽

Tammy Y N Tong ◽

Gillian K Reeves ◽

Sarah Floud ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Sleep Duration ◽

Cancer Incidence ◽

Prospective Studies ◽

Average Duration ◽

Meta Analysis ◽

Breast Cancer Incidence ◽

Weighted Average

Abstract Study Objectives To investigate the association between sleep duration and breast cancer incidence, we examined the association in a large UK prospective study and conducted a meta-analysis of prospective studies. Methods In the Million Women Study, usual sleep duration over a 24-h period was collected in 2001 for 713,150 participants without prior cancer, heart problems, stroke, or diabetes (mean age = 60 years). Follow-up for breast cancer was by record linkage to national cancer registry data for 14.3 years on average from the 3-year resurvey. Cox regression models yielded multivariable-adjusted breast cancer relative risks (RR) and 95% confidence intervals (CIs) for sleep duration categories. Published prospective studies of sleep duration and breast cancer risk were included in a meta-analysis, which estimated the inverse-variance weighted average of study-specific log RRs for short and for long versus average duration sleep. Results After excluding the first 5 years to minimize reverse causation bias in the Million Women Study, 24,476 women developed breast cancer. Compared with 7–8 h of sleep, the RRs for <6, 6, 9, and >9 h of sleep were 1.01 (95% CI, 0.95–1.07), 0.99 (0.96–1.03), 1.01 (0.96–1.06), and 1.03 (0.95–1.12), respectively. In a meta-analysis of 14 prospective studies plus the Million Women Study, including 65,410 breast cancer cases, neither short (RR < 7 h = 0.99 [0.98–1.01]) nor long (RR > 8 h = 1.01 [0.98–1.04]) versus average duration sleep was associated with breast cancer risk. Conclusions The totality of the prospective evidence does not support an association between sleep duration and breast cancer risk.

Download Full-text

Risk-Reducing Salpingo-Oophorectomy and Breast Cancer Risk Reduction in the Gynecologic Oncology Group Protocol-0199 (GOG-0199)

JNCI Cancer Spectrum ◽

10.1093/jncics/pkz075 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 2

Author(s):

Phuong L Mai ◽

Austin Miller ◽

Mitchell H Gail ◽

Steven Skates ◽

Karen Lu ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Incidence ◽

Breast Cancer Incidence ◽

Incidence Rates ◽

Pathogenic Variant ◽

Risk Reducing ◽

Cancer Risk Reduction

Abstract Background Risk-reducing salpingo-oophorectomy (RRSO) has been associated with approximately 50% breast cancer risk reduction among women with a pathogenic variant in BRCA1 or BRCA2 (BRCA1/2), a finding that has recently been questioned. Methods We estimated incidence rates of breast cancer and all cancers combined during 5 years of follow-up among participants selecting RRSO or ovarian cancer screening (OCS) among women with a BRCA1/2 pathogenic variant or strong breast and/or ovarian cancer family history. Ovarian or fallopian tube or peritoneal cancer incidence rates were estimated for the OCS group. Breast cancer hazard ratios (HRs) for time-dependent RRSO were estimated using Cox regression with age time-scale (4943 and 4990 women-years in RRSO and OCS cohorts, respectively). All statistical tests were two-sided. Results The RRSO cohort included 925 participants, and 1453 participants were in the OCS cohort (381 underwent RRSO during follow-up), with 88 incident breast cancers diagnosed. Among BRCA1/2 pathogenic variant carriers, a non-statistically significant lower breast cancer incidence was observed in the RRSO compared with the OCS cohort (HR = 0.86, 95% confidence interval = 0.45 to 1.67; P = .67). No difference was observed in the overall population or among subgroups stratified by prior breast cancer history or menopausal status. Seven fallopian tube and four ovarian cancers were prospectively diagnosed in the OCS cohort, and one primary peritoneal carcinoma occurred in the RRSO cohort. Conclusions These data suggest that RRSO might be associated with reduced breast cancer incidence among women with a BRCA1/2 pathogenic variant, although the effect, if present, is small. This evolving evidence warrants a thorough discussion regarding the impact of RRSO on breast cancer risk with women considering this intervention.

Download Full-text

The Women’s Health Initiative randomized trial of calcium plus vitamin D: Effects on breast cancer and arthralgias

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.lba6 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. LBA6-LBA6 ◽

Cited By ~ 6

Author(s):

R. T. Chlebowski ◽

K. C. Johnson ◽

C. Kooperberg ◽

A. Hubbell ◽

D. Lane ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Postmenopausal Women ◽

Breast Cancer Incidence ◽

Secondary Outcome ◽

Baseline Serum ◽

Abnormal Mammogram ◽

Joint Symptoms

LBA6 Background: Calcium (Ca) and vitamin D (D) have been associated with reduced breast cancer and breast density in observational studies. Randomized trials have not evaluated Ca/D supplementation for breast cancer prevention. Methods: We randomized 36,282 postmenopausal women without prior breast cancer from 40 WHI centers to 1000 mg of elemental calcium as calcium carbonate and 400 IU of vitamin D3 (N = 18,176) daily or matching placebo (N = 18,106); 54% were also randomized one year previously to hormone therapy (HT) or placebo; conjugated equine estrogen (CEE) plus medroxyprogesterone acetate or CEE alone (the latter for those with prior hysterectomy). Ca/D effects on hip fracture and colorectal cancer have been reported (NEJM 2006). We report here pathologically confirmed invasive breast cancer as a secondary outcome of the Ca/D trial. Baseline serum 25(OH) D levels (in 1787 women) and serial joint symptoms (pain/stiffness and hand/feet swelling 0–3 scale, in a 6% sample) were also assessed. Results: Breast cancer incidence did not differ between Ca/D and placebo randomization groups (528 and 546 cases in Ca/D and placebo; hazard ratio 0.96; 95 percent confidence interval (CI), 0.85, 1.09). While SEER stage and abnormal mammogram frequency were similar between groups, breast cancers were smaller in the Ca/D group (1.54 cm (1.23), mean (SD) versus 1.71 (1.29), P = 0.05). Total vitamin D baseline intake was associated with lower breast cancer risk in the placebo group. Baseline vitamin D (nmol per liter) deficiency was common (≥30, sufficient (n = 266), 16 ≤ 30, insufficient (277), < 16, deficient (743)) but was not related to joint pain (seen in 72.2%, 74.0%, 74.6%, of sufficiency and deficiency groups, respectively). Joint symptoms were lower in women randomized to CEE alone (P < 0.01) but did not significantly differ by Ca/D group assignment and no significant interactions were seen between HT and Ca/D. Conclusion: Among healthy postmenopausal women, Ca/D supplementation did not reduce breast cancer risk but the cancers in those randomized to Ca/D were somewhat smaller. Exogenous estrogen use but not Ca/D supplementation influences arthralgias. [Table: see text]

Download Full-text

Metformin and breast cancer risk: A meta-analysis and critical literature review.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.27_suppl.25 ◽

2012 ◽

Vol 30 (27_suppl) ◽

pp. 25-25

Author(s):

Nananda Col ◽

Leslie Ochs ◽

Vicky Springmann ◽

Aaron K Aragaki ◽

Rowan T. Chlebowski

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Literature Review ◽

Cancer Incidence ◽

Invasive Breast Cancer ◽

Meta Analysis ◽

Breast Cancer Incidence ◽

Cochrane Library ◽

Study Quality

25 Background: Observational studies have suggested that metformin, commonly used for diabetes treatment that increases insulin sensitivity and improves glycemic control, decreases the incidence of several common cancers. However, findings regarding metformin and breast cancer incidence have been mixed. To explore this issue, a systematic literature review and meta-analysis were performed with a focus on potential biases. Methods: We conducted a comprehensive literature search for all pertinent studies addressing metformin use and breast cancer risk by searching Pub Med, Cochrane Library, Scopus (which includes Embase, ISI Web of Science) using the Mesh terms: "metformin" or "biguanides" or "diabetes mellitus, type 2/therapy" and "cancer" or "neoplasms". When multiple hazard ratios (HR) or odds ratio (OR) were reported, the most adjusted estimate was used in the base-case analysis. We pooled the adjusted HR using and performed sensitivity analyses on duration of metformin use (> or < 3 years use), study quality (assessed using the GRADE system), and initial observation year of the cohort (before vs after 1997). Results: From a total of 421 citations, 13 full-text articles were considered, and 7 independent studies were included. All were observational (4 cohort and 3 case control). Our combined OR for metformin association with invasive breast cancer of all 7 studies was 0.83 (95% CI, 0.71-0.97). Funnel plot analyses did not suggest publication bias. Stronger associations were found when analyses were limited to studies estimating the impact of longer metformin duration (OR = 0.75. 95% CI, 0.62-0.91) or among studies that began observing their cohort before 1997 (OR=0.68. 95% CI, 0.55-0.84). Stratification according to study quality did not affect the combined OR but higher quality studies had smaller CI and achieved statistical significance. Interpretation is limited by the observational nature of reports and different comparison groups. Conclusions: Our analyses support a protective effect of metformin on invasive breast cancer incidence among postmenopausal women with diabetes. Clinical trials are needed to determine whether metformin reduces breast cancer risk.

Download Full-text