Background In India, as elsewhere, the incidence of gall-bladder cancer (GBC) is substantially higher in women than in men. Yet, the relevance of reproductive factors to GBC remains poorly understood. Methods We used logistic regression adjusted for age, education and area to examine associations between reproductive factors and GBC risk, using 790 cases of histologically confirmed GBC and group-matched 1726 visitor controls. We tested the interaction of these associations by genetic variants known to increase the risk of GBC. Results Parity was strongly positively associated with GBC risk: each additional pregnancy was associated with an ∼25% higher risk {odds ratio [OR] 1.26 [95% confidence interval (95% CI) 1.17–1.37]}. After controlling for parity, GBC risk was weakly positively associated with later age of menarche [postmenopausal women, OR 1.11 (95% CI 1.00–1.22) per year], earlier menopause [OR 1.03 (95% CI 1.00–1.06) per year] and shorter reproductive lifespan [OR 1.04 (95% CI 1.01–1.07) per year], but there was little evidence of an association with breastfeeding duration or years since last pregnancy. Risk alleles of single-nucleotide polymorphisms in the ABCB4 and ABCB1 genetic regions had a multiplicative effect on the association with parity, but did not interact with other reproductive factors. Conclusions We observed higher GBC risk with higher parity and shorter reproductive lifespan, suggesting an important role for reproductive and hormonal factors.

中文翻译：

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生殖因素和胆囊癌，以及常见遗传变异对这些关联的影响：印度的病例对照研究


背景 在印度，与其他地方一样，女性胆囊癌 (GBC) 的发病率明显高于男性。然而，生殖因素与 GBC 的相关性仍然知之甚少。方法 我们使用 790 例经组织学证实的 GBC 病例和分组匹配的 1726 例访客对照，使用根据年龄、教育程度和地区进行调整的逻辑回归来检查生殖因素与 GBC 风险之间的关联。我们通过已知会增加 GBC 风险的基因变异测试了这些关联的相互作用。结果 产次与 GBC 风险呈强正相关：每多妊娠一次，风险就会增加约 25% {比值比 [OR] 1.26 [95% 置信区间 (95% CI) 1.17–1.37]}。控制胎次后，GBC 风险与初潮年龄较晚 [绝经后女性，每年 OR 1.11 (95% CI 1.00–1.22)]、更年期提前 [每年 OR 1.03 (95% CI 1.00–1.06)] 呈弱正相关。和较短的生殖寿命[OR 1.04 (95% CI 1.01–1.07)每年]，但几乎没有证据表明与母乳喂养持续时间或自上次怀孕以来的年数有关。 ABCB4和ABCB1遗传区域中单核苷酸多态性的风险等位基因对与胎次的关联具有倍增效应，但不与其他生殖因素相互作用。结论 我们观察到，随着胎次的增加和生殖寿命的缩短，GBC 风险也更高，这表明生殖和激素因素发挥着重要作用。