超12年大型病例对照研究:男性不育症可将乳腺癌风险翻倍!

2022-05-26 LILYMED MedSci原创

Breast Cancer Res:男性不孕症和乳腺癌风险:英格兰和威尔士的一项全国性病例对照研究。

乳腺癌在男性中相对罕见,其病因在很大程度上是未知的。该疾病在女性中存在几种共同点,包括具有几种特定基因和已知SNP的遗传成分以及与人体测量因素的关系。Klinefelter综合征男性的风险非常高,这与人体测量学的关系一起表明,性激素相关因素可能与此有关,就像女性一样,并且唯一能够检查随后发展为乳腺癌的男性先前雌二醇水平的队列分析发现乳腺癌风险增加。

在女性中,生殖相关因素在乳腺癌病因学中很重要,但不适用于男性,但似乎值得调查男性生育能力是否与男性乳腺癌风险有关。Klinefelter综合征与不孕症有关,并且有一些但不是确定性证据表明睾丸异常也可能与男性乳腺癌风险相关。不孕症通常被定义为在定期无保护性生活至少 12 个月后无法受孕,可以是男性或女性。

然而,对男性不育症和生殖史与乳腺癌风险的关系的研究因肿瘤的罕见性而受到阻碍。因此,本研究在英格兰和威尔士进行了一项病例对照研究,涵盖了12.7年期间全国范围内的近2000例病例,并在此展示与生育和儿童有关的结果。

研究期间,确定了3187名居住在英格兰和威尔士的男性,被诊断为乳腺癌,年龄在80岁以下,其中1998位(62.7%)接受了访问。他们主要是60岁或以上的诊断,肿瘤大多是侵袭性的(92.0%)而不是原位的(8.0%),主要是雌激素受体阳性(在已知状态的人中98.5%)(表1)。病例往往比对照组年龄大,社会经济地位高,较少结婚,较少来自英格兰南部,采访时间较近;除地区外,所有这些关系都具有统计学意义,这些因素在风险分析中进行了调整。有828名男性作为非血液相关对照,其中613人(74.0%)参与, 1109名潜在世代研究对照,其中984人(88.7%)参与。

112例病例(5.6%)和80例(5.0%)对照报告他们有不孕不育问题,他们或他们的伴侣已经咨询过医生或不孕诊所(表2)。不孕症的患病率没有随年龄变化(对照组P = 0.90;病例数P = 0.39)。无孕症的比值比在统计学上没有显着提高(OR = 1.29,95% CI 0.94-1.77)。对不孕不育咨询结果进行分析后发现,从统计数据上看,被诊断为不孕不育的男性风险显著增加(OR = 2.03(1.18-3.49))。

但对于配偶为不孕症来源的患者(OR = 0.86(0.51-1.45))或未确定来源的患者(OR = 1.26(0.71-2.24))则不适用。同样的模式也适用于排除Klinefelter综合征(不孕症OR = 1.23 (0.89-1.69);(OR = 1.81(1.02-3.20)),在分析中也排除了有潜在混杂条件的男性。限制于已婚男性的分析基于较小的数字(1600例,1539例对照组),但显示了类似的结果,对于本身不育的男性具有统计学上显着的风险(p = 0.02)。如果我们将那些被诊断为精子来源或声称来源未知但被诊断为精子数量低的男性进行统计,风险也显著增加(or = 2.17 (1.29-3.67), P = 0.004)。


1615例(80.8%)患者和1423例(89.1%)对照组有孩子(表3)。无子女男性的风险显著升高(OR = 1.50 (1.21-1.86), p <0.001)。男性生第一个孩子时的年龄与风险无关(表4)。当不孕症和孩子数量拟合在一起时,随着孩子数量的变化趋势是相反的(P = 0.04),报告自己被诊断为不孕症来源的男性的OR升高较少(OR = 1.68 (0.96-2.93)),配偶为不孕症来源的男性(OR = 0.76(0.45-1.29))或未确定来源的男性(OR = 1.12(0.63-2.01)) 风险变化则无统计学意义

排除受访者认为相对不可靠的男性的敏感性分析给出了与上述相似的结果,特别是对于本身就是夫妻不育原因的男性(p = 0.04)和没有孩子的男性(p <0.001)的风险,在统计学上仍显着提高。针对饮酒、吸烟、肝病和乳腺癌家族史进行额外调整的敏感性分析并未对结果有实质性改变。

分别分析侵袭性(n = 1838)和原位(n = 160)肿瘤(表5),上述关系对于前者是存在的并且具有统计学意义(这并不奇怪,因为它们>总数的90%),但对于后者,优势比通常接近1.0,并且在任何情况下都没有统计学意义,基于小得多的数字。ER-ve的肿瘤太少,无法按ER状态进行分析(表1),但HER-2 + ve(n = 187)和− ve(n = 1376)肿瘤的结果相似,男性不育症(p = 0.04和0.01)和无子女p = 0.01和<分别为0.001)的风险显着增加。

总之,本次大型病例对照研究提供了强有力的证据,证明男性不育症与男性患乳腺癌的风险增加有关。原因尚不确定,需要进一步研究。

 

原文来源:

Swerdlow AJ, Bruce C, Cooke R, Coulson P, Jones ME. Infertility and risk of breast cancer in men: a national case-control study in England and Wales. Breast Cancer Res. 2022;24(1):29. Published 2022 May 17. doi:10.1186/s13058-022-01517-z.

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    2023-03-18 amyloid
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    2022-07-11 xugc

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