Dataset Information

Association of Genetic Markers with the Risk of Early-Onset Breast Cancer in Kazakh Women.

ABSTRACT: Breast cancer is a global health problem. It is an age-dependent disease, but cases of early-onset breast cancer (eBC) are gradually increasing. There are many unresolved questions regarding eBC risk factors, mechanisms of development and screening. Only 10% of eBC cases are due to mutations in the BRCA1/BRCA2 genes, and 90% have a more complex genetic background. This poses a significant challenge to timely cancer detection in young women and highlights the need for research and awareness. Therefore, identifying genetic risk factors for eBC is essential to solving these problems. This study represents an association analysis of 144 eBC cases and 163 control participants to identify genetic markers associated with eBC risks in Kazakh women. We performed a two-stage approach in association analysis to assess genetic predisposition to eBC. First-stage genome-wide association analysis revealed two risk intronic loci in the CHI3L2 gene (p = 5.2 × 10^-6) and MGAT5 gene (p = 8.4 × 10^-6). Second-stage exonic polymorphisms haplotype analysis showed significant risks for seven haplotypes (p < 9.4 × 10^-4). These results point to the importance of studying medium- and low-penetrant genetic markers in their haplotype combinations for a detailed understanding of the role of detected genetic markers in eBC development and prediction.

SUBMITTER: Skvortsova L

PROVIDER: S-EPMC10815330 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Association of Genetic Markers with the Risk of Early-Onset Breast Cancer in Kazakh Women.

Skvortsova Liliya L Abdikerim Saltanat S Yergali Kanagat K Mit Natalya N Perfilyeva Anastassiya A Omarbayeva Nazgul N Zhunussova Aigul A Kachiyeva Zulfiya Z Sadykova Tolkyn T Bekmanov Bakhytzhan B Kaidarova Dilyara D Djansugurova Leyla L Zhunussova Gulnur G

Genes 20240117 1

Breast cancer is a global health problem. It is an age-dependent disease, but cases of early-onset breast cancer (eBC) are gradually increasing. There are many unresolved questions regarding eBC risk factors, mechanisms of development and screening. Only 10% of eBC cases are due to mutations in the <i>BRCA1/BRCA2</i> genes, and 90% have a more complex genetic background. This poses a significant challenge to timely cancer detection in young women and highlights the need for research and awarenes ...[more]

PMID: 38254997

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Project description:ImportanceColorectal cancer (CRC) incidence and mortality among individuals younger than 50 years (early-onset CRC) are increasing. The reasons for such increases are largely unknown, although the increasing prevalence of obesity may be partially responsible.ObjectiveTo investigate prospectively the association between obesity and weight gain since early adulthood with the risk of early-onset CRC.Design, setting, and participantsThe Nurses' Health Study II is a prospective, ongoing cohort study of US female nurses aged 25 to 42 years at study enrollment (1989). A total of 85 256 women free of cancer and inflammatory bowel disease at enrollment were included in this analysis, with follow-up through December 31, 2011. Validated anthropomorphic measures and lifestyle information were self-reported biennially. Statistical analysis was performed from June 12, 2017, to June 28, 2018.ExposuresCurrent body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), BMI at 18 years of age, and weight gain since 18 years of age.Main outcomes and measuresRelative risk (RR) for incident early-onset CRC.ResultsAmong the 85 256 women studied, 114 cases of early-onset CRC were documented (median age at diagnosis, 45 years; interquartile range, 41-47 years) during 1 196 452 person-years of follow-up. Compared with women with a BMI of 18.5 to 22.9, the multivariable RR was 1.37 (95% CI, 0.81-2.30) for overweight women (BMI, 25.0-29.9) and 1.93 (95% CI, 1.15-3.25) for obese women (BMI, ≥30.0). The RR for each 5-unit increment in BMI was 1.20 (95% CI, 1.05-1.38; P = .01 for trend). Similar associations were observed among women without a family history of CRC and without lower endoscopy within the past 10 years. Both BMI at 18 years of age and weight gain since 18 years of age contributed to this observation. Compared with women with a BMI of 18.5 to 20.9 at 18 years of age, the RR of early-onset CRC was 1.32 (95% CI, 0.80-2.16) for women with a BMI of 21.0 to 22.9 and 1.63 (95% CI, 1.01-2.61) for women with a BMI of 23.0 or greater at 18 years of age (P = .66 for trend). Compared with women who had gained less than 5.0 kg or had lost weight, the RR of early-onset CRC was 1.65 (95% CI, 0.96-2.81) for women gaining 20.0 to 39.9 kg and 2.15 (95% CI, 1.01-4.55) for women gaining 40.0 kg or more (P = .007 for trend).Conclusions and relevanceObesity was associated with an increased risk of early-onset CRC among women. Further investigations among men and to elucidate the underlying biological mechanisms are warranted.

Project description:Men with familial prostate cancer and African American men are at risk for developing prostate cancer at younger ages. Genetic markers predicting early-onset prostate cancer may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset prostate cancer in a longitudinal cohort of high-risk men enrolled in prostate cancer early detection with significant African American participation.Eligibility criteria include ages 35 to 69 with a family history of prostate cancer or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped. Cox models were used to evaluate time to prostate cancer diagnosis and prostate-specific antigen (PSA) prediction for prostate cancer by genotype. Harrell's concordance index was used to evaluate predictive accuracy for prostate cancer by PSA and genetic markers.Four hundred and sixty participants with complete data and ? 1 follow-up visit were included. Fifty-six percent were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to prostate cancer diagnosis (P = 0.005) and influenced prediction for prostate cancer by the PSA (P < 0.001). When combined with PSA, rs6983561 improved predictive accuracy for prostate cancer compared with PSA alone among African American men (PSA = 0.57 vs. PSA + rs6983561 = 0.75, P = 0.03).Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing prostate cancer risk assessment. Further study is warranted to validate these findings.Genetic markers of early-onset prostate cancer have potential to refine and personalize prostate cancer early detection for high-risk men.

Dataset Information

Association of Genetic Markers with the Risk of Early-Onset Breast Cancer in Kazakh Women.

Publications

Association of Genetic Markers with the Risk of Early-Onset Breast Cancer in Kazakh Women.

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