Jian Zhao

A functional polymorphism in the poly(ADP-ribose) polymerase-1 gene is associated with platinum-based chemotherapeutic response and prognosis in epithelial ovarian cancer patients

To explore the effects of two functional genetic variants of poly(ADP-ribose) polymerase-1 (PARP-1) on the susceptibility to epithelial ovarian cancer (EOC), the platinum-based chemotherapeutic response, and the prognosis of northern Chinese patients. This case-control study included 710 EOC patients in the case group and 700 healthy women in the control group. Two polymorphisms (rs1136410 and rs8679) of PARP-1 were genotyped by polymerase chain reaction and ligase detection reaction. The genotype frequencies of rs1136410 and rs8679 were not significantly different between the case and control groups. However, the CC genotype of rs1136410 was significantly associated with a favorable response to platinum drugs. Compared with the TT genotype, the CC genotype of rs1136410 was related to a reduced risk of platinum resistance (adjusted OR: 0.40; 95% CI = 0.24-0.67; P = 0.001). In addition, multivariable analysis containing clinical variables showed that patients who carried the rs1136410 CC genotype had a significantly improved progression-free survival compared with patients who carried the TT genotype (HR = 0.67, 95% CI = 0.47-0.97, P = 0.031). The rs1136410 polymorphism may serve as a potential marker for predicting the response to platinum agents and prognosis of EOC patients treated with surgery and platinum-based chemotherapy.

Female Reproductive Traits and Late-Life Hormone-Sensitive Cancer Risk: A Mendelian Randomization Study

Abstract Ovarian reserve is a crucial component of female reproductive traits. However, the possible causal effects between ovarian reserve and hormone-sensitive cancers remain incompletely understood. In this study, two-sample Mendelian randomization (MR) analyses were performed to assess potential causal effects of reproductive traits on hormone-sensitive cancers. In addition, multivariable MR was applied to determine the potential mediation effects of reproductive traits on hormone-sensitive cancers. A 1-SD incremental increase in the anti-Müllerian hormone (AMH) level was associated with a higher risk of endometrial cancer [OR = 1.27; 95% confidence interval (CI), 1.05–1.54] but a lower risk of breast cancer (OR = 0.80; 95% CI, 0.69–0.94). Each 1-year incremental increase in age at natural menopause was associated with higher risks of breast (OR = 1.04; 95% CI, 1.02–1.05), ovarian (OR = 1.03; 95% CI, 1.01–1.05), and endometrial cancers (OR = 1.07; 95% CI, 1.04–1.09). Nulliparity increased the risk of breast cancer (OR = 1.07; 95% CI, 1.05–1.09). An elevated AMH level was indirectly associated with endometrial cancer risk with 2.67% of the effect attributed to later age at natural menopause (per 1-year increase). Each 1-year incremental increase in age at menarche was indirectly associated with endometrial cancer risk with 4.71% of the effect attributed to later age at natural menopause. The findings herein highlight AMH as a potential key biological marker for endometrial and breast cancer risk stratification. Identifying natural menopause as a key modulator may enhance our understanding of the mechanisms underlying the development of hormone-sensitive cancers. Prevention Relevance: This study identified the potential causal effects between reproductive traits and hormone-sensitive cancers. The results suggested that some reproductive traits seem to be potential risk factors for hormone-sensitive cancers, which could have utility for risk stratification and aid in understanding the mechanisms underlying the development of hormone-sensitive cancers in women.