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: 8302896
• 负责人: Yani Lu
• 金额: $ 8.4万
• 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/8302896
• 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. PUBLIC HEALTH RELEVANCE: More and more couples defer childbearing to older ages in recent decades. Although the immediate effects of advanced parental age on the health of offspring has been extensively studied, its effect on adult-onset cancer risk has not been extensively investigated. By examining the effect of parental age on the risk of common adult-onset female cancers, this study will provide critical new knowledge to clarify cancer etiology and thus provide potential targets for prevention.

描述（由申请人提供）：在过去的几十年中，育儿在西方国家经历了延误。 30岁及以上妇女的出生比例已上升到最高水平。同样，男人也倾向于将生育能力推迟到老年。 我们认为，出生时父母年龄对后代健康的影响。经过广泛研究了晚期产妇年龄（例如染色体异常）和父亲年龄（例如，Apert综合征和adnondroplasia）对后代健康的直接影响。此外，最近的研究表明，出生时的父亲年龄增加与儿童和青少年疾病有关，例如精神分裂症，儿童白血病和神经系统肿瘤。但是，尚未广泛研究出生时父母年龄对成人发作癌症风险的影响。迄今为止，与父母年龄的联系仅研究了乳腺癌，前列腺癌和血液学恶性肿瘤的研究。乳腺癌风险与高级母亲年龄和父亲年龄有关，但是前列腺癌和血液学恶性肿瘤的风险仅与晚期父亲年龄有关。较高含量的雌激素的生物学证据，随着胎龄的发展，生殖细胞突变和较高的年龄较大父亲（但不是老年母亲）的DNA损害的可能性更高，这支持了高级产妇年龄可能会增加与激素相关的癌症风险的可能性。对于大多数类型的癌症，晚期父亲年龄可能是常见的危险因素。因此，我们旨在评估父亲年龄/产妇年龄对美国妇女中10种最常见的成人发作癌（不包括非霍奇金淋巴瘤）的风险的独立影响，这会影响加利福尼亚州教师中其他潜在的癌症特定危险因素的出生秩序，社会经济状况以及其他潜在的癌症风险因素的影响（CTS）。 CTS是一项对133,479名加利福尼亚女性公立学校专业人士的前瞻性队列研究，为此目标提供了一个独特的机会，因为它既包含父母年龄信息，又包含与妇女健康相关的潜在癌症风险因素的广泛清单，尤其是与癌症风险有关。从1995年到2009年，要研究的特定癌症的事件为5007（乳房），1017（肺），843（结肠），279（直肠），1031（子宫内膜），298（甲状腺甲状腺），195（肾脏），195（肾脏），486（卵巢），337（卵巢），337（pancreatic）和761（Melan）。我们将使用多元COX比例危害模型来估计与母亲年龄和父亲年龄相关的相对风险，考虑到每个癌症结果的癌症特异性风险因素。该项目的成功完成将解决有关父母年龄对成人癌症风险的影响的差距。它将提供进一步的见解 追求父母年龄和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以阐明病因的生物标志物，从而为预防提供潜在的目标。 公共卫生相关性：近几十年来，越来越多的夫妻将生育于年龄较大。尽管已经对高级父母时代对后代健康的直接影响进行了广泛的研究，但尚未对其对成年癌症风险的影响进行广泛研究。通过检查父母年龄对常见成年女性癌症风险的影响，这项研究将提供关键的新知识，以阐明癌症的病因，从而为预防提供潜在的靶标。