Parental age at birth and risk of adult-onset cancer in female offspring

父母的出生年龄和女性后代成年发病癌症的风险

• 批准号: 8464031
• 负责人: Yani Lu
• 金额: $ 7.9万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8464031
• 关键词: Accounting; Achondroplasia; Address; Adolescent; Adult; Affect; Age; Apert syndrome; Apoptosis; Autistic Disorder; Biological; Biological Markers; Birth; Birth Order; Breast; California; Cancer Etiology; Cell division; Child; Childhood; Childhood Leukemia; Chromosome abnormality; Cohort Studies; Colon; Country; Couples; Cox Proportional Hazards Models; DNA Damage; DNA Repair; Daughter; Development; Disease; Endometrial; Endometrial Carcinoma; Enrollment; Epigenetic Process; Estrogens; Etiology; Family history of; Fathers; Female; Fertilization; Genetic; Genomic Imprinting; Germ Cells; Gestational Age; Goals; Growth; Health; Hematologic Neoplasms; Hormones; Human; Hyperactive behavior; Insulin-Dependent Diabetes Mellitus; Kidney; Knowledge; Lead; Length; Link; Lung; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Malignant neoplasm of thyroid; Maternal Age; Mothers; Mutagens; Mutation; Nervous System Neoplasms; Non-Hodgkin' s Lymphoma; Onset of illness; Oocytes; Outcome; Ovarian; Pancreas; Parental Ages; Participant; Paternal Age; Perinatal mortality demographics; Predisposition; Pregnancy; Prevention; Property; Prospective Studies; Puberty; Publishing; Regulation; Relative Risks; Renal carcinoma; Research; Resources; Risk; Risk Factors; Role; Schizophrenia; Schools; Socioeconomic Status; Soil; Specimen; Spermatogonia; Telomerase; Testing; Thyroid Gland; Time; Woman; Women' s Health; Work; advanced maternal age; aged; base; cancer diagnosis; cancer initiation; cancer risk; cancer type; carcinogenesis; child bearing; cohort; experience; follow-up; high risk; hormone related cancer; insight; male; malignant breast neoplasm; melanoma; member; men; offspring; prospective; rectal; response; teacher; telomere; transmission process

DESCRIPTION (provided by applicant): Childbearing has experienced delays in Western countries in the last several decades. The proportion of births to women aged 30 years and above has risen to its highest level. Similarly, men also tend to defer childbearing to older ages. We believe that there will be measureable effects of parental age at birth on the health of offspring. The immediate effects of advanced maternal age (e.g., chromosomal abnormalities) and paternal age (e.g., Apert syndrome and achondroplasia) on the health of offspring have been extensively studied. In addition, recent studies have shown that increased paternal age at birth is associated with childhood and adolescent disorders such as schizophrenia, childhood leukemias and nervous system tumors. However, the effects of parental age at birth on the risk of adult-onset cancer have not been extensively investigated. To date, the association with parental age has only been studied for breast cancer, prostate cancer and hematological malignancies. Breast cancer risk is associated with both advanced maternal age and paternal age, but the risk of prostate cancer and hematological malignancies are only associated with advanced paternal age. Biological evidence of higher levels of circulating estrogens with advancing gestational age and higher chance of germ cell mutations and DNA damage from older fathers (but not older mothers) supports the possibility that advanced maternal age may increase the risk of hormone-related cancers; advanced paternal age may be a common risk factor for most types of cancer. Therefore, we aim to evaluate the independent effect of paternal age/maternal age on the risk of the 10 most common adult-onset cancers (not including non- Hodgkin lymphoma on which we have published) among U.S. women, accounting for the effects of birth order, socioeconomic status, and other potential cancer-specific risk factors in the California Teachers Study (CTS). The CTS, a prospective cohort study of 133,479 female California public school professionals, provides a unique opportunity for this aim because it contains both parental age information and an extensive list of potential cancer risk factors related to women's health and particularly to cancer risk. From 1995 through 2009, the incident cases for the specific cancers to be studied are 5007 (breast), 1017 (lung), 843 (colon), 279 (rectal), 1031 (endometrial), 298 (thyroid), 195 (kidney), 486 (ovarian), 337 (pancreatic) and 761 (melanoma). We will use multivariate Cox proportional hazards model to estimate the relative risks associated with maternal age and paternal age, considering cancer-specific risk factors for each cancer outcome. Successful completion of this project will address a gap in knowledge regarding the effect of parental age on adult-onset cancer risk. It will provide insight to further pursue the biological mechanisms between parental age and cancer risk. The long-term goal of the research is to explore biomarkers that link parental age and cancer risk to clarify etiology, and thus provide potential targets for prevention.

描述（由申请人提供）：在过去的几十年里，西方国家的生育经历了延迟。30岁及以上妇女的生育比例已上升到最高水平。同样，男子也倾向于将生育推迟到较大年龄。 我们相信，父母出生时的年龄对后代的健康会产生可衡量的影响。高龄产妇的直接影响（例如，染色体异常）和父亲年龄（例如，Apert综合征和软骨发育不全）对后代健康的影响已被广泛研究。此外，最近的研究表明，父亲出生时年龄的增加与儿童和青少年精神分裂症、儿童白血病和神经系统肿瘤等疾病有关。然而，父母出生时的年龄对成人发病癌症风险的影响尚未得到广泛研究。到目前为止，仅研究了乳腺癌、前列腺癌和血液恶性肿瘤与父母年龄的关系。乳腺癌风险与高龄母亲和父亲年龄相关，但前列腺癌和血液恶性肿瘤的风险仅与高龄父亲相关。随着孕龄的增加，循环雌激素水平升高，生殖细胞突变的机会增加，来自年长父亲（但不是年长母亲）的DNA损伤也增加，这一生物学证据支持高龄产妇可能会增加患乳腺癌相关癌症的风险;高龄父亲可能是大多数癌症的常见风险因素。因此，我们的目的是评估父亲年龄/母亲年龄对美国女性中10种最常见的成人发病癌症（不包括我们已发表的非霍奇金淋巴瘤）风险的独立影响，考虑出生顺序、社会经济地位和加州教师研究（CTS）中其他潜在癌症特异性风险因素的影响。CTS是一项对133，479名加州公立学校女性专业人员进行的前瞻性队列研究，为实现这一目标提供了一个独特的机会，因为它包含了父母年龄信息和与女性健康相关的潜在癌症风险因素的广泛列表，特别是癌症风险。从1995年到2009年，研究的特定癌症的发病病例为5，007例（乳腺癌）、1，017例（肺癌）、843例（结肠癌）、279例（直肠癌）、1，031例（子宫内膜癌）、298例（甲状腺癌）、195例（肾癌）、486例（卵巢癌）、337例（胰腺癌）和761例（黑色素瘤）。我们将使用多变量考克斯比例风险模型来估计与母亲年龄和父亲年龄相关的相对风险，考虑每种癌症结局的癌症特异性风险因素。该项目的成功完成将解决关于父母年龄对成人发病癌症风险影响的知识差距。它将提供洞察力， 研究父母年龄与癌症风险之间的生物学机制。该研究的长期目标是探索将父母年龄和癌症风险联系起来的生物标志物，以澄清病因，从而为预防提供潜在的靶点。