scholarly journals The Menstrual Cycle Related Hormone Variations and Breast Cancer Risk: A Novel Theory

2020 ◽  
pp. 1-6
Author(s):  
Liang Xiaohui ◽  
Liang Xiaohui ◽  
Nicholas Taylor ◽  
Vixey Fang ◽  
Xiao Zhang

Background: The cumulative and excessive exposures to estrogen contributing to increased risk of breast cancer may be misleading. Methods: We proposed a novel theory to highlight that exposure to unstable estrogen levels may play a critical role in determining breast cancer risk among females as the change of endocrine environment may pose a risky environment to breast tissues for carcinogenesis. Particularly, we considered the menstrual cycle related estrogen variation (MCREV) as the primary hazard to breast cancer among females. Results: To describe MCREV, its intensity was defined as the difference between the highest and the lowest levels of estrogen within a menstrual cycle; its timing was defined as age at menarche and age at pregnancies (i.e. timing of cessation of exposure to this hazard); and its frequency and duration can both be defined as the total number of menstrual cycles, which is influenced by many factors including age of menarche, age of menopause, average length of one menstrual cycle, and durations and number of pregnancies and breastfeeding. Conclusions: The proposed MCREV theory may identify women at high-risk of breast cancer at an earlier age. The development of breast cancer might be weakened if suitable techniques to reduce the MCREV become clinically available. This novel theory opens a new door in breast cancer prevention and management.

2018 ◽  
Author(s):  
Siddhartha P. Kar ◽  
Irene L. Andrulis ◽  
Hermann Brenner ◽  
Stephen Burgess ◽  
Jenny Chang-Claude ◽  
...  

AbstractObservational studies suggest that higher birth weight (BW) is associated with increased risk of breast cancer in adult life. We conducted a two-sample Mendelian randomisation (MR) study to assess whether this association is causal. Sixty independent single nucleotide polymorphisms (SNPs) known to be associated at P < 5 × 10-8 with BW were used to construct (1) a 41-SNP instrumental variable (IV) for univariable MR after removing SNPs with pleiotropic associations with other breast cancer risk factors and (2) a 49-SNP IV for multivariable MR after filtering SNPs for data availability. BW predicted by the 41-SNP IV was not associated with overall breast cancer risk in inverse-variance weighted (IVW) univariable MR analysis of genetic association data from 122,977 breast cancer cases and 105,974 controls (odds ratio = 0.86 per 500 g higher BW; 95% confidence interval: 0.73—1.01). Sensitivity analyses using four alternative methods and three alternative IVs, including an IV with 59 of the 60 BW-associated SNPs, yielded similar results. Multivariable MR adjusting for the effects of the 49-SNP IV on birth length, adult height, adult body mass index, age at menarche, and age at menopause using IVW and MR-Egger methods provided estimates consistent with univariable analyses. Results were also similar when all analyses were repeated after restricting to estrogen receptor-positive or -negative breast cancer cases. Point estimates of the odds ratios from most analyses performed indicated an inverse relationship between genetically-predicted BW and breast cancer. Thus, there is little evidence from MR to suggest that the previously observed association between higher BW and increased risk of breast cancer in adult life is causal.


2020 ◽  
Author(s):  
Vasudha Sambyal ◽  
Kamlesh Guleria ◽  
Ruhi Kapahi ◽  
Mridu Manjari ◽  
Meena Sudan ◽  
...  

Abstract Background: Angiogenesis is a complex and coordinated process regulated by different growth factors and is one of the hallmark features of cancer. VEGF is one of the most important endothelial cell mitogen and has a critical role in normal physiological and tumor angiogenesis. The objective of this study was to investigate the potential association of haplotypes of six VEGF polymorphisms with breast cancer risk in North-West Indians. Methods: Samples of 250 breast cancer patients and 250 age and gender matched controls were genotyped for VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms. Haplotypes were generated to determine the better contribution of VEGF polymorphisms to breast cancer risk. Results: Haplotypes CDTCCC (OR = 0.56, 95%CI, 0.38-0.81; p = 0.003) and CDTGCC (OR = 0.63, 95%CI, 0.44-0.92; p = 0.018) of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with decreased risk of breast cancer. CDTCCC haplotype was also significantly associated with reduced risk of breast cancer in pre and post menopausal as well as both obese and non obese patients. Haplotype CDTGCC was marginally associated (p = 0.07) with reduced risk of breast cancer in non-obese patients as compared with non-obese controls where as haplotype AICGTC was marginally associated (p = 0.09) with reduced risk of breast cancer in obese patients when compared with non-obese patients. The CDTGCC haplotype was significantly associated with increased risk of breast cancer in premenopausal obese patients (OR = 1.98, 95%CI, 1.10-3.56; p = 0.02). Conclusions: Our data indicated that CDTCCC and CDTGCC haplotypes of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with breast cancer risk in North-West Indians. Further studies on multiethnic groups with larger sample size are required to confirm our results.


2020 ◽  
Author(s):  
Vasudha Sambyal ◽  
Kamlesh Guleria ◽  
Ruhi Kapahi ◽  
Mridu Manjari ◽  
Meena Sudan ◽  
...  

Abstract Background: Angiogenesis is a complex and coordinated process regulated by different growth factors and is one of the hallmark features of cancer. VEGF is one of the most important endothelial cell mitogen and has a critical role in normal physiological and tumor angiogenesis. The objective of this study was to investigate the potential association of haplotypes of six VEGF polymorphisms with breast cancer risk in North-West Indians. Methods: Samples of 250 breast cancer patients and 250 age and gender matched controls were genotyped for VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms. Haplotypes were generated to determine the better contribution of VEGF polymorphisms to breast cancer risk. Results: Haplotypes CDTCCC (OR = 0.56, 95%CI, 0.38-0.81; p = 0.003) and CDTGCC (OR = 0.63, 95%CI, 0.44-0.92; p = 0.018) of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with decreased risk of breast cancer. CDTCCC haplotype was also significantly associated with reduced risk of breast cancer in pre and post menopausal as well as both obese and non obese patients. Haplotype CDTGCC was marginally associated (p = 0.07) with reduced risk of breast cancer in non-obese patients as compared with non-obese controls where as haplotype AICGTC was marginally associated (p = 0.09) with reduced risk of breast cancer in obese patients when compared with non-obese patients. The CDTGCC haplotype was significantly associated with increased risk of breast cancer in premenopausal obese patients (OR = 1.98, 95%CI, 1.10-3.56; p = 0.02). Conclusions: Our data indicated that CDTCCC and CDTGCC haplotypes of VEGF -2578C/A, -2549I/D, -460T/C, +405C/G, -7C/T and +936C/T polymorphisms were significantly associated with breast cancer risk in North-West Indians. Further studies on multiethnic groups with larger sample size are required to confirm our results.


2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
Jonathan D. Herman ◽  
Sarah M. Herman

4 Background: A woman’s understanding of her breast cancer risk is an important precursor for care. A valid estimate allows for greater opportunity to consider early detection modalities and chemopreventive medications. The USPSTF recently encouraged women who have an increased risk of developing a first breast cancer and a low risk of side effects to take tamoxifen or raloxifen. The objective of this study is to compare patients' perceived breast cancer risk with their calculated risk and then parse those findings by ethnicity. Methods: Anonymous, IRB approved, pre-piloted questionnaires were filled out by women at 21 mammography centers on Long Island. The survey included questions about patient demographics, patient’s estimates of their own breast cancer risk and personal risk factors. Results: 9,873 respondents qualified for inclusion in our analysis. Women were asked to quantify their breast cancer risk by age 90. Overall, 707 (9.4%) were in line with their risks, 3,359 (44.7%) underestimated risk and 3,454 (45.9%) overestimated their risk. When parsed by ethnicity, of the 781 African Americans, 8.7% were in line, 57.6% underestimated risk, and 33.7% overestimated risk. Of the 245 Asians, 10.2% were in line, 58.8% underestimated risk, and 31% overestimated risk. Of the 427 Hispanics, 8.9% were in line, 50.4% underestimated risk, and 40.8% overestimated risk. Of the 6850 Caucasians, only 10.2% were in line, 38.6% underestimated risk, and 51.3% overestimated risk. Conclusions: Most women lack accurate knowledge of their own breast cancer risk – 90.6% overall. When parsed by ethnicity, while there was a statistical difference between groups, the difference was not important because overall understanding was very low. Caucasian women tended to overestimate their risk compared with other ethnic groups, possibly resulting in unnecessary anxiety. African American and Hispanics tended to underestimate risk compared with Caucasians, possibly resulting in underutilization of available resources. Patients must have a better understanding of their personal risk. Study findings should help refocus educational efforts because increased knowledge of breast cancer risk will enable providers to tailor an individual’s medical treatment plan.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Vasudha Sambyal ◽  
Kamlesh Guleria ◽  
Ruhi Kapahi ◽  
Mridu Manjari ◽  
Meena Sudan ◽  
...  

 Abstract Background Angiogenesis is a complex and coordinated process regulated by different growth factors and is one of the hallmark features of cancer. VEGF is one of the most important endothelial cell mitogen and has a critical role in normal physiological and tumor angiogenesis. The objective of this study was to investigate the potential association of haplotypes of six VEGF polymorphisms with breast cancer risk in North-West Indians. Methods Samples of 250 breast cancer patients and 250 age and sex matched controls were genotyped for VEGF −2578C/A, −2549I/D, −460T/C, +405C/G, −7C/T and +936C/T polymorphisms. Haplotypes were generated to determine the better contribution of VEGF polymorphisms to breast cancer risk. Results Haplotypes CDTCCC (OR = 0.56, 95%CI, 0.38–0.81; p = 0.003) and CDTGCC (OR = 0.63, 95%CI, 0.44–0.92; p = 0.018) of VEGF −2578C/A, −2549I/D, −460T/C, +405C/G, −7C/T and +936C/T polymorphisms were significantly associated with decreased risk of breast cancer. CDTCCC haplotype was also significantly associated with reduced risk of breast cancer in pre and post menopausal as well as both obese and non obese patients. Haplotype CDTGCC was marginally associated (p = 0.07) with reduced risk of breast cancer in non-obese patients as compared with non-obese controls where as haplotype AICGTC was marginally associated (p = 0.09) with reduced risk of breast cancer in obese patients when compared with non-obese patients. The CDTGCC haplotype was significantly associated with increased risk of breast cancer in premenopausal obese patients (OR = 1.98, 95%CI, 1.10–3.56; p = 0.02). Conclusions Our data indicated that CDTCCC and CDTGCC haplotypes of VEGF −2578C/A, −2549I/D, −460T/C, +405C/G, −7C/T and +936C/T polymorphisms were significantly associated with breast cancer risk in North-West Indians. Further studies on multiethnic groups with larger sample size are required to confirm our results.


2018 ◽  
Vol 64 (1) ◽  
pp. 95-101
Author(s):  
Nazira Aldasheva ◽  
Vyacheslav Kipen ◽  
Zhaynagul Isakova ◽  
Sergey Melnov ◽  
Raisa Smolyakova ◽  
...  

Basing on Multifactor Dimensionality Reduction method we showed that polymorphic variants p.Q399R (rs25487, XRCC1) and p.P72R (rs1042522, TP53) correlated with increased risk of breast cancer for women from the Kyrgyz Republic and the Republic of Belarus. Cohort for investigation included patients with clinically verified breast cancer: 117 women from the Kyrgyz Republic (nationality - Kyrgyz) and 169 - of the Republic of Belarus (nationality - Belarusians). Group for comparison included (healthy patients without history of cancer pathology at the time of blood sampling) 102 patients from the Kyrgyz Republic, 185 - from the Republic of Belarus. Respectively genotyping of polymorphic variants p.Q399R (rs25487, XRCC1) and p.P72R (rs1042522, TP53) was done by PCR-RFLP. Analysis of the intergenic interactions conducted with MDR 3.0.2 software. Both ethnic groups showed an increase of breast cancer risk in the presence of alleles for SNPs Gln p.Q399R (XRCC1) in the heterozygous state: for the group “Kyrgyz” - OR=2,78 (95% CI=[1,60-4,82]), p=0,001; for the group “Belarusians” - OR=1,85 (95% СІ=[1Д1-2,82], p=0,004. Carriers with combination of alleles Gln (p.Q399R, XRCC1) and Pro (p.P72R, TP53) showed statistically significance increases of breast cancer risk as for patients from the Kyrgyz Republic (OR=2,89, 95% CI=[1,33-6,31]), so as for patients from the Republic of Belarus (OR=3,01, 95% CI=[0,79-11,56]).


2020 ◽  
Vol 35 (6) ◽  
pp. 1253-1255
Author(s):  
Zeev Blumenfeld ◽  
Norbert Gleicher ◽  
Eli Y Adashi

Abstract Whereas longstanding dogma has purported that pregnancies protect women from breast cancer, a recent meta-analysis now mandates reconsideration since it reported an actual higher breast cancer risk for more than two decades after childbirth before the relative risk turns negative. Moreover, the risk of breast cancer appears higher for women having their first birth at an older age and with a family history and it is not reduced by breastfeeding. The process of obtaining informed consent for all fertility treatments, therefore, must make patients aware of the facts that every pregnancy, to a small degree, will increase the short-term breast cancer risk. This observation may be even more relevant in cases of surrogacy where women agree to conceive without deriving benefits of offspring from assuming the risk, thus creating a substantially different risk-benefit ratio. Consequently, it appears prudent for professional societies in the field to update recommendations regarding consent information for all fertility treatments but especially for treatments involving surrogacy.


2011 ◽  
Vol 26 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Nupur Mukherjee ◽  
Nilanjana Bhattacharya ◽  
Satyabrata Sinha ◽  
Neyaz Alam ◽  
Runu Chakravarti ◽  
...  

The adenomatous polyposis coli (APC) and mutated in colorectal cancer (MCC) genes are key regulatory genes of the Wnt/β-catenin signaling pathway, which are independently involved in maintaining low levels of β-catenin in the cell. In addition to genetic and epigenetic alterations, some genetic polymorphisms in the genes associated with the Wnt signaling pathway have been reported to be associated with an increased risk of cancer, including breast cancer. In the present study we analyzed the association of genotype and haplotype status of two single nucleotide polymorphisms (SNPs), rs2229992 and rs11283943, in the APC and MCC genes, respectively, with an increased risk of breast carcinogenesis in a breast cancer and control population from eastern India. We observed a significant association of the rs11283943 SNP with increased breast cancer risk. Two specific haplotypes involving the minor allele of rs11283943 were found to be associated with an increased breast cancer risk. Kaplan-Meier curves showed a significant association of the 2–2 genotype (genotype homozygous for the rs11283943 minor allele) with decreased survival (p=0.045) of the breast cancer patients in our study, in particular patients with early-onset BC.


2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Mandy Goldberg ◽  
Aimee A. D’Aloisio ◽  
Katie M. O’Brien ◽  
Shanshan Zhao ◽  
Dale P. Sandler

Abstract Background Earlier age at menarche is an established risk factor for breast cancer. While age at menarche has been fairly stable over the past half-century, age at breast development (thelarche) has continued to decrease. Recently, earlier age at thelarche and a longer time between thelarche and menarche (pubertal tempo) were shown to be associated with increased breast cancer risk. Our objective was to examine how breast cancer risk was associated with pubertal timing and tempo in a prospective US cohort. Methods Women ages 35–74 years without a history of breast cancer, but who had a sister previously diagnosed with breast cancer, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported their ages at thelarche and menarche. Pubertal tempo was age at menarche minus age at thelarche. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each pubertal milestone and risk of breast cancer (invasive or ductal carcinoma in situ) using Cox proportional hazards regression. We examined whether associations between age at thelarche and breast cancer risk were modified by birth cohort, race/ethnicity, weight at age 10, and extent of breast cancer family history, as characterized by a Bayesian score based on first-degree family structure. Results During follow-up (mean = 9.3 years), 3295 eligible women were diagnosed with breast cancer. Early ages at thelarche (HR = 1.23, 95% CI 1.03–1.46 for < 10 vs. 12–13 years) and menarche (HR = 1.10, 95% CI 1.01–1.20 for < 12 vs. 12–13 years) were positively associated with breast cancer risk. Pubertal tempo was not associated with breast cancer risk (HR = 0.99, 95% CI 0.97–1.02 per 1-year longer tempo). When considering early thelarche (< 10 years) and early menarche (< 12 years) jointly, women with both had a 30% greater risk of breast cancer compared with women with neither risk factor (95% CI 1.07–1.57). The association between age at thelarche and breast cancer risk did not significantly vary by birth cohort, race/ethnicity, childhood weight, or Bayesian family history score. Conclusions Earlier ages at thelarche and menarche may enhance susceptibility to breast carcinogenesis. Age at thelarche is an important risk factor to consider given secular trends towards earlier development.


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