Increased Risk of Breast Cancer Associated With CHEK2*1100delC

Purpose CHEK2*1100delC heterozygosity has been associated with increased risk of breast, prostate, and colorectal cancer in case-control studies. We tested the hypothesis that CHEK2*1100delC heterozygosity in the general population increases the risk of cancer in general, and breast, prostate, and colorectal cancer in particular. Patients and Methods We performed a prospective study of 9,231 individuals from the Danish general population, who were observed for 34 years, and we performed a case-control study including 1,101 cases of breast cancer and 4,665 controls. Results Of the general population, 0.5% were heterozygotes and 99.5% were noncarriers. In the prospective study, multifactorially adjusted hazard ratios by CHEK2*1100delC heterozygosity versus noncarriers were 1.2 (95% CI, 0.7 to 2.1) for all cancers, 3.2 (95% CI, 1.0 to 9.9) for breast cancer, 2.3 (95% CI, 0.6 to 9.5) for prostate cancer, and 1.6 (95% CI, 0.4 to 6.5) for colorectal cancer. In the case-control study, age-matched odds ratio for breast cancer by CHEK2*1100delC heterozygosity versus noncarriers was 2.6 (95% CI, 1.3 to 5.4). The absolute 10-year risk of breast cancer in CHEK2*1100delC heterozygotes amounted to 24% in women older than 60 years undergoing hormone replacement therapy, with a body mass index of 25 kg/m2 or higher. Conclusion CHEK2*1100delC heterozygosity is associated with a three-fold risk of breast cancer in women in the general population.

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Comparing and assessing the reported penetrance of cancer susceptibility genes for breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1520 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1520-1520

Author(s):

Kanhua Yin ◽

Danielle Braun ◽

Ankur Tiwari ◽

Jin Wang ◽

Preeti Singh ◽

...

Keyword(s):

Breast Cancer ◽

General Population ◽

Case Control Study ◽

Cancer Susceptibility ◽

Susceptibility Genes ◽

Case Control ◽

Cancer Risks ◽

Cancer Susceptibility Genes ◽

Increased Risk ◽

Control Study

1520 Background: It is critical for oncologists to be aware of unbiased and interpretable cancer risks (i.e., penetrance) in carriers with germline pathogenic variants in cancer susceptibility genes. However, relevant literature is large and varies significantly in study design, patient ascertainment, and types of risk estimates reported. This heterogeneity can cause inconsistent conclusions between studies and create barriers for clinicians to understand and apply them in practice. To further understand the current literature, we assessed penetrance studies associated with non-BRCA breast cancer susceptibility genes based on study design and ascertainment adjustment. Methods: We used a validated natural language processing-based abstract classifier to identify all penetrance studies regarding eleven genes: ATM, BARD1, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, RECQL, STK11, and TP53. Relevant studies were then manually annotated as “with ascertainment adjustment” if a study was based on: (1) a general population; (2) a pedigree analysis or a family-based study with appropriate ascertainment adjustment; or (3) a hospital-based study or a panel testing analysis with well-matched cases and controls. Results: A total of 49 penetrance studies were identified, with a median of nine studies for each gene (range: 4-16). The case-control study was the dominant study type, accounting for over 80% in five genes, 50% in two genes, and 18% to 43% in the other four genes. The proportion of studies with ascertainment adjustment was generally low (mean: 33%) and varied widely between different genes (7% to 80%). Contradictory breast cancer risks (no increased risk vs. significantly increased risk) were found in eight genes (73%) (Table). The most common ascertainment bias identified was a case-control study with cases (patients) who had a strong family history but using general population controls. Conclusions: Ascertainment bias is common in penetrance studies, but few studies adjust for it appropriately. Clinicians should be aware of this issue, and new methods are warranted to select unbiased risk estimates, synthesize them, and provide the accurate general-population penetrance. [Table: see text]

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Increased risk of ovarian cancer in integrin β3 Leu33Pro homozygotes

Endocrine Related Cancer ◽

10.1677/erc.1.01083 ◽

2005 ◽

Vol 12 (4) ◽

pp. 945-952 ◽

Cited By ~ 6

Author(s):

S E Bojesen ◽

S K Kjær ◽

E V S Høgdall ◽

B L Thomsen ◽

C K Høgdall ◽

...

Keyword(s):

Ovarian Cancer ◽

Prospective Study ◽

Case Control Study ◽

Cox Regression ◽

Conditional Logistic Regression ◽

Case Control ◽

Hazard Ratios ◽

Increased Risk ◽

Risk Of Cancer ◽

Control Study

We previously demonstrated that integrin β3 Leu33Pro homozygotes have an increased risk of cancer, possibly most pronounced for ovarian cancer. We now test the latter hypothesis in case-control and prospective studies. We genotyped 463 Danish women with ovarian cancer, and 4291 women from the Danish general population. Calculation of odds ratios by conditional logistic regression was performed in the case-control study (n=463 + 3543), and of ovarian cancer incidence, log-rank statistics and hazard ratios by Cox regression in the prospective study (n=4291) with 9.5-year follow-up. In the case-control study matched for age and marital status, the odds ratio for ovarian cancer in homozygotes versus non-carriers was 1.6 (95% confidence interval: 1.0–2.6). In the prospective study with 28 incident ovarian cancers, non-carriers and homozygotes had incidences of 7 (4–11) and 30 (10–92) per 10 000 person-years (log-rank P=0.02). The age-adjusted hazard ratio for ovarian cancer in homozygotes versus non-carriers was 3.9 (1.1–13). Risk of ovarian cancer did not differ between heterozygotes and non-carriers in either study. Integrin β3 Leu33Pro homozygotes have an increased risk of ovarian cancer.

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Methylation of WT1, CA10 in peripheral blood leukocyte is associated with breast cancer risk: a case-control study

10.21203/rs.3.rs-27678/v2 ◽

2020 ◽

Author(s):

Anqi Ge ◽

Song Gao ◽

Yupeng Liu ◽

Hui Zhang ◽

Xuan Wang ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Case Control Study ◽

Case Control ◽

Elevated Risk ◽

Luminal B ◽

Increased Risk ◽

Risk Of Cancer ◽

Control Study

Abstract Background: Studies have shown that abnormal changes of specific-gene DNA methylation in leukocytes may be associated with an elevated risk of cancer. However, associations between the methylation of the zinc-related genes, WT1 and CA10, and breast cancer risk remain unknown. Methods: The methylation of WT1 and CA10 was analyzed by methylation-sensitive high-resolution-melting (MS-HRM) in a case-control study with female subjects (N=959). Logistic regression was used to analyze the associations, and propensity score (PS) method was used to adjust confounders. Results: The results showed that WT1 hypermethylation was associated with an increased risk of breast cancer, with an odds ratio (OR) of 3.07 [95% confidence interval (CI): 1.67-5.64, P<0.01]. Subgroup analyses showed that WT1 hypermethylation was specifically associated with an elevated risk of luminal A subtype (OR=2.62, 95% CI: 1.11-6.20, P=0.03) and luminal B subtype (OR=3.23, 95% CI: 1.34-7.80, P=0.01). CA10 hypermethylation was associated with an increased risk of luminal B subtype (OR=1.80, 95% CI: 1.09-2.98, P=0.02). Conclusion: The results of the present study suggest that the hypermethylation of WT1 methylation in leukocytes is significantly associated with an increased risk of breast cancer. The hypermethylation of WT1 is associated with an increased risk of luminal subtypes of breast cancer, and the hypermethylation of CA10 is associated with an increased risk of luminal B subtype of breast cancer.

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Tamoxifen use correlates with increased risk of hip fractures in older women with breast cancer: A case-control study in Taiwan

Geriatrics and Gerontology International ◽

10.1111/ggi.13568 ◽

2018 ◽

Vol 19 (1) ◽

pp. 56-60 ◽

Cited By ~ 4

Author(s):

Shih-Chang Hung ◽

Kuan-Fu Liao ◽

Hung-Chang Hung ◽

Cheng-Li Lin ◽

Po-Chang Lee ◽

...

Keyword(s):

Breast Cancer ◽

Older Women ◽

Hip Fractures ◽

Case Control Study ◽

Case Control ◽

Increased Risk ◽

Control Study

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Association of a Novel KIF26B Gene Polymorphism with Susceptibility to Schizophrenia and Breast Cancer: A Case-Control Study

Iranian Journal of Public Health ◽

10.18502/ijph.v50i2.5359 ◽

2021 ◽

Author(s):

Saman SARGAZI ◽

Milad HEIDARI NIA ◽

Shekoufeh MIRINEJAD ◽

Mahdiyeh MOUDI ◽

Mahdiyeh JAFARI SHAHROUDI ◽

...

Keyword(s):

Breast Cancer ◽

Case Control Study ◽

De Novo ◽

Case Control ◽

Amplification Refractory Mutation System ◽

Salting Out ◽

Current Case ◽

Increased Risk ◽

Mutation System ◽

Control Study

Background: KIF26B gene is found to play essential roles in regulating different aspects of cell proliferation and development of the nervous system. We aimed to determine if rs12407427 T/C polymorphism could affect susceptibility to schizophrenia (SZN) and breast cancer (BC), the two genetically correlated diseases. Methods: The current case-control study was performed from Aug 2018 to Dec 2018. Briefly, 159 female pathologically confirmed BC cases referring to Alzahra Hospital, Isfahan, Iran, and 102 psychologically confirmed SZN patients (60 males and 42 females) admitted to Baharan Hospital, Zahedan, Iran, were enrolled. Using the salting-out method, genomic DNA was extracted, and variants were genotyped using allele-specific amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method. Results: The results revealed a significant association between the KIF26B rs12407427 codominant CT (P=0.001), CC (P=0.0001), dominant CT+CC, and recessive CC (P=0.001) genotypes with the risk of developing SZN. Significant correlations were also found regarding rs12407427 and BC susceptibility in different inheritance models, including over-dominant CT (P=0.026), dominant CT+CC (P=0.001), recessive CC (P=0.009), and codominant CT and CC (P=0.001) genotypes. The over-presence of the C allele was also correlated with an increased risk for SZN (P=0.0001) and BC (P=0.0001). Finally, computational analysis predicted that T/C variation in this polymorphism could change the binding sites in proteins involved in splicing. Conclusion: rs12407427 T/C as a de novo KIF26B variant might be a novel genetic biomarker for SZN and/or BC susceptibility in a sample of the Iranian population.

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Lifetime alcohol consumption and breast cancer: a case–control study in Finland

Public Health Nutrition ◽

10.1017/s1368980000000033 ◽

2000 ◽

Vol 3 (1) ◽

pp. 11-18 ◽

Cited By ~ 12

Author(s):

Satu Männistö ◽

Mikko Virtanen ◽

Vesa Kataja ◽

Matti Uusitupa ◽

Pirjo Pietinen

Keyword(s):

Breast Cancer ◽

Alcohol Consumption ◽

Postmenopausal Women ◽

Case Control Study ◽

Premenopausal Women ◽

Case Control ◽

Total Lifetime ◽

Increased Risk ◽

Control Study ◽

Current Alcohol

AbstractObjectiveTo study the association between lifetime alcohol consumption and the risk of breast cancer.Design and settingA case–control study carried out in eastern Finland. Information about alcohol consumption was obtained by two methods: a self-administered food frequency questionnaire (FFQ) including alcohol consumption during the previous 12 months, and a lifetime alcohol consumption questionnaire (AQ) which was administered by the study nurse.SubjectsThe study consisted of 301 breast cancer cases (25–75 years old) and 443 population controls.ResultsThe subjects reported higher current alcohol consumption in the AQ compared to the FFQ. According to the AQ, premenopausal cases consumed on average 28 g and controls 24 g alcohol week−1; in postmenopausal women the values were 15 and 14 g, respectively. About 30% of premenopausal and 60% of postmenopausal women were classified as non-drinkers. The correlation for current alcohol consumption between the FFQ and the AQ was 0.80 in premenopausal women but only 0.40 in postmenopausal women. Current alcohol consumption seemed to influence the reporting of total lifetime alcohol consumption. Current alcohol consumption was not associated with the risk of breast cancer either in premenopausal or postmenopausal women; neither were associations found between alcohol consumption at age of first use, use before the age of 30, or total lifetime alcohol consumption and the risk of breast cancer.ConclusionsOn average, one to three drinks per week did not increase the risk of breast cancer in this study. Consumption levels were, however, too low to exclude increased risk with high regular consumption. Further research is necessary on lifetime alcohol consumption.

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Association between shiftwork and the risk of colorectal cancer in females: a population-based case–control study

Occupational and Environmental Medicine ◽

10.1136/oemed-2017-104657 ◽

2018 ◽

Vol 75 (5) ◽

pp. 344-350 ◽

Cited By ~ 11

Author(s):

Wa Mwenga Walasa ◽

Renee N Carey ◽

Si Si ◽

Lin Fritschi ◽

Jane S Heyworth ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Case Control Study ◽

Early Morning ◽

Population Based ◽

Case Control ◽

Colorectal Cancer Risk ◽

Adverse Health Outcomes ◽

Increased Risk ◽

Control Study

ObjectiveResearch indicates that shiftwork may be associated with increased risks of adverse health outcomes, including some cancers. However, the evidence of an association between shiftwork and colorectal cancer risk is limited and inconclusive. Further, while several possible pathways through which shiftwork might result in cancer have been proposed, few studies have taken these factors into account. We investigated the association between two types of shiftwork (graveyard shiftwork and early-morning shiftwork) and six mechanistic shiftwork variables (including light at night and phase shift) and the risk of colorectal cancer among females in an Australian population-based case–control study. Graveyard shiftwork was the primary exposure of interest.MethodsParticipants (350 cases and 410 controls) completed a lifetime occupational history, and exposure to each of the eight shiftwork variables was assigned to participants through a job exposure matrix. We used logistic regression to calculate odds ratios (OR) and corresponding 95% confidence intervals (CI) for the association between different shiftwork variables and the risk of colorectal cancer, adjusting for potential demographic, lifestyle and medical confounders.ResultsWorking in an occupation involving long-term exposure (>7.5 years) to graveyard shiftwork was not associated with colorectal cancer risk (adjusted OR 0.95, 95% CI 0.57 to 1.58). Similarly, no increased risks of colorectal cancer were seen for any of the other seven shiftwork variables examined.ConclusionsNo evidence of an increased risk of colorectal cancer among females who had worked in occupations involving shiftwork was observed in this study.

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Serum selenium level and cancer risk: a nested case-control study

Hereditary Cancer in Clinical Practice ◽

10.1186/s13053-019-0131-7 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Steven A. Narod ◽

Tomasz Huzarski ◽

Anna Jakubowska ◽

Jacek Gronwald ◽

Cezary Cybulski ◽

...

Keyword(s):

Cancer Risk ◽

Case Control Study ◽

Case Control ◽

Serum Selenium ◽

Baseline Serum ◽

Increased Risk ◽

Low Selenium ◽

Nested Case Control ◽

Risk Of Cancer ◽

Control Study

Abstract Background Epidemiologic studies have demonstrated a relationship between selenium status and cancer risk among those with low selenium levels. It is of interest to prospectively evaluate the relationship between selenium and cancer among women who reside in a region with ubiquitously low selenium levels. Methods We performed a nested case-control study of baseline serum selenium levels and cancer risk using data and biological samples from 19,573 females that were participants in a biobanking initiative between 2010 and 2014 in Szczecin Poland. Cases included women with any incident cancer (n = 97) and controls (n = 184) were women with no cancer at baseline or follow-up. Serum selenium was quantified using mass spectroscopy. Results The odds ratio associated being below the cutoff of 70.0 μg/L compared to a level above 70.0 μg/L was 2.29 (95% CI 1.26–4.19; P = 0.007). The risks for women in the two middle categories were similar and suggests that the normal range be between 70 μg/L and 90 μg/L. There was evidence for an increased risk of cancer among women in the highest category of selenium levels (i.e., > 90 μg/L), but this association did not achieve statistical significance (OR = 1.63; 95%CI 0.63–4.19; P = 0.31). Conclusions Results from this study suggest that suggest that the optimum serum level of selenium in women living in Poland should be between 70 μg/L and 90 μg/L.

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