Factors Associated With Testicular Cancer Risk Among New American Military Recruits During Wartime

The risk of testicular cancer is thought to be higher among men seeking infertility treatment compared with the general population. Confirmation of this risk in a large US cohort of at-risk patients is lacking. This study explored the association between male infertility and subsequent development of testicular cancer in a US-based cohort. A total of 51 461 couples evaluated for infertility from 1967 to 1998 were recruited from 15 California infertility centers. We linked data on 22 562 identified male partners to the California Cancer Registry. The incidence of testicular cancer in this cohort was compared with the incidence in an age-matched sample of men from the general population using the Surveillance Epidemiology and End Results program. We analyzed the risk for testicular cancer in men with and without male factor infertility using a Cox proportional hazards regression model. Thirty-four post-infertility-diagnosis cases of histologically confirmed testicular cancer were identified. Men seeking infertility treatment had an increased risk of subsequently developing testicular cancer (standardized incidence ratio, 1.3; 95% confidence interval, 0.9-1.9), with a markedly higher risk among those with known male factor infertility (2.8; 1.5-4.8). In multivariable analysis, men with male factor infertility were nearly 3 times more likely to develop testicular cancer compared with those without (hazard ratio, 2.8; 95% confidence interval, 1.3-6.0). Men with male factor infertility have an increased risk of subsequently developing testicular cancer, suggesting the existence of common etiologic factors for infertility and testicular cancer.

(2009). Penn researchers discover genetic risk factor for testicular cancer: Gene is associated with a three-fold increase in risk for testicular cancer. Cancer Biology & Therapy: Vol. 8, No. 12, pp. 1083-1082.

Translating Testicular Cancer Epidemiology into Clinical Practice

Risks of breast and testicular cancers in young adult twins in England and Wales: evidence on prenatal and genetic aetiology

Association between male genital anomalies and adult male reproductive disorders: a population-based data linkage study spanning more than 40 years

The present case-control study was undertaken to investigate the association between exposure to maternal hormones and risk of testicular germ-cell cancer by histologic subgroups. Cases were males, aged 16 to 59 years, diagnosed with testicular germ-cell cancer in Ontario between 1987 and 1989. Histologic review was performed on all eligible cases for the purpose of categorizing cases as seminoma or non-seminoma (the latter classified 2 ways, with and without tumors containing seminoma). Risk factor data were collected on 502 cases, 346 case mothers, 975 age-matched controls, and 522 control mothers. Exogenous hormone exposure was associated with elevated risk (OR = 4.9, 95% CI 1.7-13.9). Several additional risk factors were associated with risk of testicular cancer: bleeding and threatened miscarriage (OR = 0.6, 95% CI 0.3-1.0), maternal cigarette smoking (12+ cigarettes/day OR = 0.6, 95% CI 0. 4-1.0). pre-term birth (OR = 1.6, 95% CI 1.0-2.5), and treatment for undescended testicle (OR = 8.0, 95% CI 3.2-20.0). First births were associated with elevated risk (OR = 1.7, 95% CI 1.0-2.8) among mothers below the age of 24 years at conception. There was little evidence that risk factors differed by histologic subgroup. We found evidence that exposure to maternal hormones, particularly estrogens, is associated with testicular germ-cell cancer risk. Not only does exposure to elevated levels (exogenous hormone use, pre-term birth, and first births among young mothers) increase risk but also exposure to relatively lower levels (heavy cigarette consumption and, perhaps, bleeding and threatened miscarriage) may decrease cancer risk.

Testicular Germ Cell Cancer Incidence in an Immigration Perspective, Denmark, 1978 to 2003

BackgroundGuidelines recommend biopsies for men <50 years with testicular microlithiasis and cancer risk factors to rule out germ cell neoplasia in situ. Limited data support this practice.ObjectivesTo clarify the significance of testicular microlithiasis by examining pathological findings in men with testicular microlithiasis.Materials and methodsWe reviewed charts of men diagnosed with testicular microlithiasis at a tertiary referral center from 2013 to 2023. Patient characteristics, clinical findings, and cancer risk factors including testicular hypotrophy (volume ≤12 mL), infertility, and cryptorchidism were recorded. Men with unknown fertility were offered semen analyses. Histological findings from testicular biopsies and subsequent cancers were noted. Primary endpoints were rates of germ cell neoplasia in situ and testicular cancer diagnoses.ResultsWe included 334 men (median age 33 years, range 16–73 years): 27 had testicular hypotrophy, 18 infertility, 25 cryptorchidism, and 56 multiple risk factors. The remaining 208 men had no apparent risk factors. Of these 36 were had reduced semen quality. Overall, 137 of 334 men (41%) underwent biopsies, with germ cell neoplasia in situ in 10 cases (7.3%, 95% confidence interval 3.6%–13%). Four had multiple risk factors (hypotrophy and infertility in two; hypotrophy, infertility, and cryptorchidism in two), three had hypotrophy alone, one had infertility, and two had reduced semen quality. Germ cell neoplasia in situ was unilateral in all cases and only found in testicles with testicular microlithiasis. Unilateral orchiectomy was performed in all germ cell neoplasia in situ cases, with hypotrophy found in all but one. Over a median follow‐up of 4.7 years (range 1.16–11.49 years), testicular cancer developed in three men (0.9%, 95% confidence interval 0.19%–2.6%).DiscussionGerm cell neoplasia in situ was only detected in cases with both testicular microlithiasis and testicular hypotrophy, and the rate of subsequent cancer development was low. This suggests that testicular microlithiasis alone does not increase cancer risk in otherwise morphologically normal testicles.ConclusionBiopsies should only be considered in men with incidental testicular microlithiasis if the testicular size is reduced.

The present study aimed at exploring the relations between body mass index (BMI) and stature and testicular cancer in a huge Norwegian cohort with measured height and weight. Height and weight were measured in 600,000 Norwegian men aged 14-44 years during 1963-2001. Results from parts of the study cohort have been reported previously. During follow-up, 1,357 testicular cancers were registered. Relative risks (RRs) of testicular cancer were estimated using Cox proportional hazards regression. The risk of testicular cancer decreased with adult BMI. Compared with men with normal BMI, overweight and obese men had a relative risk of cancer of 0.89 (95% CI: 0.77-1.03) and 0.83 (95% CI: 0.58-1.17). The relative risk of testicular cancer per unit increase in BMI was 0.97 (95% CI: 0.95-1.00). The risk of testicular cancer was not associated with adolescent BMI. A moderate increase in risk of seminomas was seen with increasing adult height. Compared with men with height 170-79 cm, men with height 180 cm and above had a relative risk of 1.17 (95% CI: 1.00-1.37).

Prepubertal orchiopexy for cryptorchidism may be associated with lower risk of testicular cancer: Walsh TJ, Dall’Era MA, Croughan MS, Carroll PR, Turek PJ, Department of Urology, University of California San Francisco, San Francisco, CA

PurposeTo evaluate the association between commonly measured serum biomarkers of inflammation and penile and testicular cancer risk in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study.Materials and methodsA total of 205,717 subjects had baseline measurements of C-reactive protein, albumin, and haptoglobin. The association between quartiles and dichotomised values of inflammatory markers and penile and testicular cancer risk were analysed by using multivariate Cox proportional hazard models.ResultsA total of 125 men were diagnosed with testicular cancer and 50 with penile cancer during a mean follow-up of 20.3 years. No statistically significant trends were seen between serum inflammatory markers and risk of penile cancer, but higher albumin levels increased the risk of testicular cancer [HR for albumin (g/L): 1.10 (95% CI: 1.03–1.18)]. However, this trend was not observed when using medical cut-offs of albumin.ConclusionsIn the present study, we did not find support for an association between commonly used markers of inflammation and risk of testicular or penile cancer. The role of inflammation may be more complicated and require assessment of more specialised measurements of inflammation in future studies.

No risk factor other than cryptorchidism has been consistently associated with testicular cancer, and the influence of diet on testicular cancer risk has not been extensively explored. A few studies have found increased testicular cancer risk in men whose diets are high in fat, red meats, and milk or low in fruits and vegetables. We evaluated the relationship of dietary factors and risk of testicular cancer and also examined whether this risk varied by type of testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center (Houston, TX) of 160 testicular cancer cases diagnosed between 1990 and 1996 and 136 friend-matched controls. The results of multivariable logistic regression analysis showed that after adjustment for age, education, income, ethnicity, cryptorchidism, and total daily calories, increasing total fat, saturated fat, and cholesterol consumption were associated with increasing risk of nonseminoma testicular cancer, with odds ratios (ORs) for the highest vs. the lowest quartiles of 6.3, 5.3, and 4.6, respectively. The risk for seminoma testicular cancer marginally increased with increasing intake of total fat and saturated fat, with ORs for the highest vs. lowest quartiles of 1.9 and 2.1, respectively. Higher total fat consumption was nearly significantly related to increased mixed germ cell tumor risk, with an OR for highest vs. lowest quartile of 4.2. This study supports the hypothesis that diet (particularly high fat consumption) increases testicular cancer risk in young men. However, the small sample size and the possibility that these observations may be due to bias indicate that the relationship of diet and testicular cancer risk needs to be further examined within a prospective or incident case-control study.

The association between undescended testis (cryptorchidism) and testicular cancer is established, but it is not known whether the risk of testicular cancer among men with unilateral maldescent is increased in both testes, or only on the undescended side. This is a meta-analysis of 11 case-control studies and 1 cohort study that all assessed the risk of testicular cancer separately for the undescended and descended testis. We used fixed-effects meta-analysis to calculate pooled estimates and 95% confidence intervals (CIs) for the relative risk. Of 199 tumors in men with unilateral cryptorchidism, 158 (79%) were on the ipsilateral side and 41 (21%) on the contralateral side. The pooled relative risks for testicular cancer in the ipsilateral and contralateral testis were 6.33 (95% CI, 4.30 to 9.31) and 1.74 (95% CI, 1.01 to 2.98), respectively. We conclude that in 1-sided undescended testis, the risk of testicular cancer may be increased in both testes, although to a much greater extent on the ipsilateral side.

Background: None of population-based epidemiological studies to date had a large enough sample size to show familial risk of testicular cancer (TC) by patients’ and their relatives’ age at diagnosis and also by rare histological subtypes. Objective: We aimed to estimate absolute and relative risk of TC in relatives of TC patients by age at diagnosis in patients and their relatives and histology subtypes. Design: A joint population-based cohort study. Setting and Participants: A cohort of 97,402 first-degree relatives of 21,254 TC patients who were diagnosed between1955 and 2010 in five European countries was followed for cancer incidence. Outcome Measurements and Statistical Analysis: Standardized incidence ratios (SIRs) were estimated using histology-, age-, period-, and country-specific incidence rates as the reference. The lifetime cumulative risks also were calculated. Results and Limitations: The lifetime cumulative risk of TC in brothers of a patient with TC was 2.3%, which represents 4-fold increased risk (SIR = 4.1, 95%CI = 3.6-4.6) over the general population risk. TC in a father increased the risk up to 2-fold in his son (95%CI = 1.7-2.4; lifetime risk 1.2%) and vice versa. When there were ≥2 TC patients diagnosed in a family, lifetime TC risk for relatives was 10-11%. Depending on age at diagnosis, twins had 9-74% lifetime risk of TC. Family history of most of the histological subtypes of TC increased the risk for concordant and most of the discordant subtypes. There was a tendency toward concordant age at diagnosis of TC among relatives. Conclusions: This study provides clinically relevant age-specific cancer risk estimates for family members of TC patients. Familial TC cases tended to develop TC at an age close to age at diagnosis of TC among their relatives, which is the novel finding of this study. Citation Format: Elham Kharazmi, Kari Hemminki, Eero Pukkala, Kristina Sundquist, Laufey Tryggvadottir, Steinar Tretli, Jørgen H. Olsen, Mahdi Fallah. Cancer risk in relatives of testicular cancer patients by histology type and age at diagnosis: a joint study from five Nordic countries. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2743. doi:10.1158/1538-7445.AM2015-2743

The Link between Male Genital Anomalies and Adult Male Reproductive Disorders: A Population-Based Data Linkage Study Spanning Over 40 Years