Parity, reproductive factors, and the risk of pancreatic cancer in women.
ABSTRACT Incidence rates for pancreatic cancer are consistently lower in women than in men. Previous studies suggest that reproductive factors, particularly parity, may reduce pancreatic cancer risk in women. We examined parity, breast feeding history, age at first birth, menstrual factors, and exogenous hormone use in relation to pancreatic cancer risk in a prospective cohort study of women. Information on parity and other reproductive factors was assessed by questionnaires in 1976 and updated biennially. Multivariate relative risks were adjusted for cigarette smoking, body mass index, diabetes, and height. During 22 years of follow-up (1976-1998), 115,474 women contributed 2.4 million years of person time, and 243 cases of pancreatic cancer were identified. Compared with nulliparous women, the relative risk of pancreatic cancer was 0.86 [95% confidence interval (CI), 0.55-1.36] for women with 1-2 births, 0.75 (95% CI, 0.48-1.17) for 3-4 births, and 0.58 (95% CI, 0.34-0.98) for those with >/=5 births after adjusting for other factors. An analysis for linear trend indicates a 10% reduction in risk for each birth (P(trend) = 0.008). Other reproductive factors and exogenous hormone use were not significantly related to pancreatic cancer risk. In this large prospective cohort of women, parity was associated significantly with a reduced risk of pancreatic cancer. Additional studies should examine the physiological or hormonal changes underlying pregnancy or childbirth that may explain this finding.
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ABSTRACT: Life-history theory predicts a tradeoff between reproductive effort and lifespan. It has been suggested that this tradeoff is a result of reproductive costs accelerating senescence of the immune system, leading to earlier death. Longevity costs of reproduction are suggested for some human populations, but whether high reproductive effort leads to impaired immune function is unknown. We examined how reproductive effort affected postreproductive survival and the probability of dying of an infectious disease in women born in preindustrial Finland between 1702 and 1859. We found that mothers delivering twins had reduced postreproductive survival after age 65. This effect arose because mothers of twins had a higher probability of succumbing to an infectious disease (mainly tuberculosis) than mothers delivering singletons. The risk among mothers of twins of dying of an infectious disease was further elevated if mothers had started reproducing early. In contrast, neither female postreproductive survival nor the risk of succumbing to an infectious disease was influenced by the total number of offspring produced. Our results provide evidence of a long-term survival cost of twinning in humans and indicate that the mechanism mediating this cost might have been accelerated immunosenescence.Proceedings of the National Academy of Sciences 09/2004; 101(33):12391-6. DOI:10.1073/pnas.0402215101 · 9.81 Impact Factor
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ABSTRACT: There is little doubt that cigarette smoking remains a major environmental health risk that humans are facing in the twenty-first century. Cigarette smokers are more likely to develop many forms of diseases than nonsmokers, including cancers and vascular diseases. With the availability of the human genome sequence, we become more aware of the genetic contributions to these common diseases, especially the interactive relations between environmental factors (e.g., smoking) and genes on disease susceptibility, development, and prognosis. Although smoking is responsible for up to 30% of pancreatic cancers and about 10% of cases are ascribed to genetic reasons, some genetic variants do not predispose carriers to disease development unless they are exposed to a specific adverse environment such as smoking. This smoke-gene interaction could potentially be responsible for most of the cases. Certain polymorphisms in genes such as CYP1A1 have been shown particularly sensitive to smoking-induced pathogenesis, including pancreatic cancer and atherosclerosis. We found that individuals with CYP1A1 CC genotype had a more than three fold increase in risk for severe coronary atherosclerosis when they smoked. Patients with endothelial nitric oxide synthase (eNOS) intron 4 27 repeat homozygotes were more likely to develop severe coronary stenosis when they smoked. On the other hand, DNA variants at the eNOS gene also dictate how smoking affects the expression of eNOS. We showed that GSTM1 deficiency was not involved in smoking-induced vascular diseases, but p53 polymorphisms tended to modify the disease severity in smokers. We are still at an early stage of defining the pairs and mechanisms of smoke-gene interaction, and this etiologic mechanism may hold great potential for risk assessment, treatment strategy, and prognostic predictions.World Journal of Surgery 04/2005; 29(3):344-53. DOI:10.1007/s00268-004-7819-0 · 2.35 Impact Factor
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ABSTRACT: This paper provides a review of the literature associating maternal age at first birth and cancer. Potential mechanisms explaining associations between maternal age at first birth and cancer are also discussed. Systematic review of English language literature using searches on established databases (e.g., Medline, Popline) and the references of materials identified in these databases. Older age (typically defined as 35 years or older) at first birth is associated with increased risk of breast and brain cancers. Conversely, younger age (typically defined as 19 years or younger) at first birth is associated with an increased risk of cervical and endometrial cancers. There is an unclear correlation between maternal age at first birth and site-specific malignancies such as ovarian, colorectal, thyroid, pancreatic, and kidney cancers. Causal mechanisms linking age at first birth and cancer were identified and reported for breast, brain, cervical, and endometrial cancers. Older age at first birth increases the risk for breast and brain cancers but decreases the risk of cervical and endometrial cancers.Gynecologic Oncology 04/2005; 96(3):583-93. DOI:10.1016/j.ygyno.2004.11.038 · 3.69 Impact Factor